Medicinska fakultetens interna webbplats


Halvtidskontroller EMV


Half-time Review
Department of Experimental Medical Science

Oscar van der Have

Department of Experimental Medical Science
Research Group Vessel Wall Biology

Time: May 30th at 11:00
Location: C1241a at BMC

Main supervisor: Karin Tran-Lundmark
Reviewers: Anja Meissner and Doris Cunha

Title: Vascular Remodeling in the Pulmonary and Fetal Circulation, and its Implications for Children with End-stage Heart Disease


Background Elevated pulmonary vascular resistance (PVR) is the hemodynamic hallmark of pulmonary arterial hypertension (PAH) and an important feature of the fetal circulation, allowing for shunting of blood through the ductus arteriosus (DA). Failure of the DA to close post-partum, generating a patent DA (PDA), is associated with development of PAH if left unmanaged. Deposition of extracellular matrix (ECM) is seen in occlusive vascular conditions in both systemic, pulmonary, and fetal arteries. Large aggregating proteoglycans such as aggrecan and versican are ECM molecules vital for arterial wall homeostasis given their biomechanical properties, as well as being facilitators of cell signaling, migration and differentiation. Accumulation of aggrecan and versican has been implicated in the development of aortic dissection, but also appears to be a conserved mechanism underlying physiological closure of umbilical arteries in mammals. Clinically, cut-off levels for PVR and the importance of vasoreactivity in pediatric patients under evaluation for heart transplantation needs further investigation.


The overall aim of these studies is to understand vascular remodeling processes in PAH (I) and DA (II), focusing on the production and turn-over of aggrecan and versican. Additionally, we aim to review the present knowledge on implications of elevated PVR in the work-up for cardiac transplantation in children (III) and how it affects long-term survival and complication incidence in this population (IV).

Method and results

Histology and synchrotron-based computed-tomography was applied to paraffin-embedded PAH tissue and the Sugen5416/Hypoxia rat model of pulmonary hypertension, enabling characterization of specific subtypes of end-stage vascular lesions in PAH (papers 1 and 5). A similar approach, with the addition of gene expression analysis, RT-qPCR and RNAscope ISH, was used to demonstrate accumulation of aggrecan in vascular lesions of patients with idiopathic PAH (manuscript 2) and is ongoing for studies of aggrecan/versican in the DA. A retrospective, registry-based approach is used to investigate outcomes following pediatric heart transplantation in the Scandinavian countries and a questionnaire-based study has been performed to highlight international heterogeneity in the management of PVR in pediatric patients with end-stage left heart disease (manuscript 3).


The studies have revealed previously unknown histopathological features of PAH and identified aggrecan as a potential contributor to vascular remodeling in this setting. Furthermore, a need for additional studies on clinical management of elevated PVR in relation to cardiac transplantation has been identified.

Tomas Roos

Tomas’ profile in LU research portal

Time: April 6th 13:00
 Location: BMC I1341

Main supervisor: Gunnar Gouras
Co-supervisor: Oskar Hansson
Opponents: Jia-yi Li och Sara Linse


Title: Prion-like Properties of Amyloid-beta and Alpha-synuclein


Many neurodegenerative disorders are thought to be due to misfolding and aggregation of certain proteins and peptides. In Alzheimer’s disease one finds amyloid-beta and tau aggregates, and in Parkinson’s disease alpha-synuclein. It is not known how the misfolded forms of these proteins spread throughout the brain. One hypothesis is that these proteins have prion-like properties. That is once one protein misfolds it serves as a template for misfolding of more proteins. 

Results and method

Inhibiting cell-cell transfer of prion-like proteins could slow disease progression. We therefore studied how alpha-synuclein can transfer cell-cell in vitro using the fluorescent markers GFP and mCherry.

Amyloid-beta plaques are extracellular and there is some controversy about the role of intracellular amyloid-beta. In our second study we induced cells in culture to constitutively produce prion-like amyloid-beta and analyzed the conformation of the amyloid-beta in those cells with PAGE under denaturing and non-denaturing conditions as well as with FTIR. This intracellular species of prion-like amyloid-beta was a soluble oligomer.

In our third study we, like other groups, accelerated plaque formation in 5xFAD mice by intracerebral injection of mouse Alzheimer’s disease brain homogenate. But we, unlike other groups, also studied changes in intracellular amyloid-beta. We found that intracellular amyloid-beta was affected in adjacent areas to where the plaques were induced but also in synaptically connected areas, namely the entorhinal cortex. We also found that intracellular aggregation of intracellular amyloid-beta disrupted the normal equilibrium of extra and intracellular amyloid-beta and increased the production of amyloid-beta.


Our data point to an important and early role of intracellular prion-like amyloid-beta in the pathogenesis of Alzheimer’s disease.

Manar Alyamani

Jan Marsal Research Group

Time: Friday March 18, 2022, 09:00
Location: BMC D15, Sven Gardell
Zoom link:

Main supervisor: Jan Marsal
Co-supervisors: Jonas Erjefält and Mohammad Kadivar
Opponents: Katharina Lahl and Klas Sjöberg


Title: Quantitative image analysis for evaluation of the degree and type of immunological activity in the intestine of mice and humans

Inflammatory bowel diseases (IBD; Crohn's disease [CD] and ulcerative colitis [UC]) are complex immune-mediated inflammatory diseases with a relapsing/remitting course. The pathogenesis has not been fully elucidated but is thought to involve a dysregulated immune response, directed towards a subset of commensal enteric bacteria, which arises in genetically predisposed individuals that are exposed to elusive environmental risk factors. There is significant heterogeneity among IBD patients, and currently there are no tools to predict therapeutic responses or disease prognosis for individual patients or subgroups.

Research question/Method
We are investigating the inflammatory state of the intestinal mucosa in human and murine tissues, primarily using immunohistochemistry (IHC) with quantitative image analysis (QIA). A method called Additive Multiple Labelling Cytochemistry (AMLC), which was developed for lung tissue, has been adapted for analysis of intestinal biopsies. Ileocolonic biopsies have been collected from patients with CD or UC, and control subjects. Various immune mediators and cells within the epithelium and lamina propria, respectively, have been quantified using QIA. A protocol for murine tissue was also optimized, investigating tissues from alkaline sphingomyelinase (NPP7) knockout (KO), heterozygous (HZ), and wildtype (WT) mice to examine a potential immunological role for NPP7 in the gut.

Preliminary results
We have developed a new immunohistological index to assess the disease activity in both CD and UC. The index is based on the quantification of selected immune cell-populations in the epithelial and lamina propria compartments, respectively; and quantitates the degree of inflammation in intestinal mucosa. Processing of the more complex AMLC-data is ongoing. In another project, we are investigating the expression of Ki-67 in the intestinal mucosa from IBD-patients and controls, to examine whether Ki-67 may be useful as a biomarker for IBD disease activity. In the NPP7 KO-mice project, four gut-related organs have been examined with QIA of the main immune cell-populations. The data show differences between the KO and WT mice, primarily in the T-cell populations, suggesting a role for NNP7 in the immune-regulation of gut.

Our research may contribute to a better understanding of the inflammatory processeses underlying IBD; to describe novel subgroups of IBD patients based on immunological characterization; to improve prediction of therapeutic response to specific treatments in individual patients or subgroups; to identify patients with poor prognosis that should be treated more aggressively; to improve monitoring of IBD disease activity; and to be able to more stringently evaluate the effects of therapy including the many new and expensive agents.

Sofia Mogren

Respiratorisk cellbiologi

Time: 22a mars kl 09:00
Place: Dora Jacobsson, BMC

Main supervisor: Cecilia Andersson
Co-supervisor: Lena Uller och Leif Bjermer
Opponents: Anna-Karin Larsson Callerfelt och Arne Egesten


Title: The role of Mast Cells and their Mediators in Repair Responses in Baseline Conditions and Chronic Respiratory Diseases.

Chronic respiratory diseases (CRD), including asthma and chronic obstructive pulmonary disease (COPD), affect several million people globally and constitute a major health burden as leading cause of disability and mortality. Impaired and dysregulated epithelial barrier function as well as destruction of alveolar compartments are central elements in the pathogenies of CRD. Increased density of mast cells (MCs) are associated with CRD, where MCs are active players in a wide range of immunological settings. However, the MC-epithelial crosstalk in the context of wound healing and barrier function remains incompletely understood in both health and disease. 

Research questions and method
This PhD project aims to investigate the impact of MC mediators, such as tryptase and chymase, on bronchial epithelial cells, alveolar epithelial cells and pulmonary fibroblasts with focus on barrier functions such as wound healing, cell migration and proliferation as well as tissue remodeling. In vitro experiments are carried out to study the effect on gene, protein, and functional levels (holographic live cell imaging). Future studies will focus on these cellular mechanisms in a clinical and in vivo setting.

Preliminary results
In the first and published study, we found that MC tryptase improved bronchial epithelial wound healing via enhanced migration and proliferation that was regulated via protease activator receptor 2 (PAR2). In the second peer-reviewed study, we found that MC tryptase and chymase induce a dual regulatory response in alveolar epithelial cells in events related to the urokinase plasminogen activation system. Preliminary results indicate that MC mediator have a pivotal role on epithelial barrier and fibroblast functions.

Epithelial function, together with an increased MC presence and activity, are profoundly altered in CRD and associated with pathology of the lung. Despite a vast health burden caused by CRD much remains unknown regarding the MC-epithelial interaction in these diseases. Investigations of mechanisms linked to MC-epithelial crosstalk could lead to new more specific treatment strategies in relevant clinical settings. Data from our studies suggest a pivotal role of MCs in health and disease.

Published papers
Sofia Mogren, Frida Berlin, Sangeetha Ramu, Asger Sverrild, Celeste Porsbjerg, Lena Uller, Cecilia K Andersson. Mast cell tryptase enhances wound healing by promoting migration in human bronchial epithelial cells. Cell Adh Migr. 2021 Dec;15(1):202-214.  doi: 10.1080/19336918.2021.1950594. PMID: 34308764.

Efthymios Tsimtsirakis

Time: February 28, 2022 at 13:00
Location: BMC D15, Sven Gardell
Zoom link 
Main supervisor: Alex Evilevitch
Co-supervisor: Peter Jönsson
Opponents: Vinay Swaminathan and Rainer Timm 


Title: Physical mechanisms of Herpesvirus infection dynamics and latency. 

Background: Herpes Simplex Virus Type 1 (HSV-1) is a neurotropic virus that initially infects epithelial cells. Once inside the host cell, the viral capsid containing the genome is transported to the nucleus via the microtubular network. Upon attachment to the nuclear pore complex (NPC), the capsid portal vertex is cleaved and the viral genome, driven by intracapsid pressure, is ejected. Then the infection is directed towards a lytic, where the viral genome is replicated, or latent outcome where the genome remains as an epitope in the host nucleus. We investigate the mechanics of DNA in the viral capsid and in the host cell nucleus. Both viral and host cell DNA structures undergo mechanical changes during infection which affect the replication cycle of the virus and in turn affect the course of infection.

Research question/Method: We use confocal fluorescence microscopy and image analysis developed in our lab to track viral DNA and number of viral capsids bound to nuclei. Furthermore, to investigate the mechano-structural changes of the host nucleus following infection using Atomic Force Microscopy (AFM). We have developed a system of HSV-1 capsids bound to isolated nuclei that allows for accurate measurements of the nuclear mechanical responses. 

Preliminary results: We have recently shown that the capsid binding ability is affected by the number of specific proteins interacting with the NPCs. Furthermore, we have shown that our reconstituted isolated nuclei/capsid system allows for mechanical measurements of the interactions between the virus DNA and the host genome during infection. Preliminary AFM data have shown that upon capsid attachment, the nucleus chromatin stiffness is altered.

Significance: Understanding the mechanical forces that drive herpesvirus infection has given rise to the design of novel broad-spectrum antiviral drugs that take advantage of the physical properties of the viral genome and block infection while evading the development on drug resistance. 

Johanna Norrlid

Time:  Tuesday March 1 2022, 11:00 (AM)

Location: BMC, building D: Borgström-salen

Title: Sensorimotor information processing in health and in a model of psychosis

Main supervisor: Henrik Jörntell

Co-supervisor: Alexander Santillo and Fredrik Bengtsson

Opponents: Germund Hesslow and Pouya Movahed


Sensorimotor information processing in health and in a model of psychosis

Background: To date, little is known of how the brain processes information. Understanding how the brain processes information forms the basis for our understanding of normal phenomena such as thoughts and perception but also disease symptoms such as hallucinations. Connectivity and activity, or ‘state’, of the neocortical network are important determinants of how information is processed in the network. This PhD project aims to investigate the basic mechanisms of information processing, and perception, in the neocortical network by exploring the network’s neuronal connectivity and state, in health and in a model of psychosis.

Method: Neocortical data are collected through the patch clamp technique in vivo in anesthetized rats. Through intracellular whole-cell recordings and loose patch recordings of pyramidal neurons in the primary somatosensory cortex, the spontaneous activity and the activity in response to complex tactile stimulation is recorded. In one of the projects, the intracellular recordings are made before and after administration of a hallucinogenic substance.

Preliminary results: In summary, our findings, firstly, do not show evidence of a canonical microcircuitry in the neocortex. Instead, the network connectivity appears to be unique to each neuron. Secondly, the neocortical network state reveals a multi-structure impacting the response of each single neuron to repeated stimulation of the same tactile input pattern. This variation in internal state hence has a high-dimensional impact on the information processing, and perception. Thirdly, upon the injection of a hallucinogenic substance, the network activity appears to enter into a lower dimensionality state with a more stereotypical signaling pattern.

Significance: Understanding how the brain processes information is the basis for understanding all the brain's functions, in health as well as in disease. The presented project explores this at a high level of detail in the neocortical neuronal network and provides the basis for creating better models to understand the basic mechanisms of perception. In the project, the basic mechanisms of perception are disrupted with a hallucinogenic substance, to gain a deeper understanding of the pathophysiology of schizophrenia.

Published papers

I: Mogensen H, Norrlid J, Enander JMD, Wahlbom A, Jörntell H. Absence of repetitive correlation patterns between pairs of adjacent neocortical neurons in vivo. Frontiers in Neural Circuits. 2019;13:48

II: Norrlid J, Enander JMD, Mogensen H, Jörntell H. Multi-structure Cortical States Deduced From Intracellular Representations of Fixed Tactile Input Patterns. Frontiers in Cellular Neuroscience. 2021 Jun 14;15:677568.

Chang Li

Time: February 23 2022, 10:00Zoom Title: Neuronal and glial plasticity in the dopamine-denervated striatum: implications for the pathophysiology of Parkinson’s DiseaseMain supervisor: Angela Cenci NilssonCo-supervisor:Tim Fieblinger, Daniella OttossonOpponents: Gunnar Gouras, Iben Lundgaard 


Neuronal and glial plasticity in the dopamine-denervated striatum: implications for the pathophysiology of Parkinson´s disease.

Background: Parkinson's disease (PD) is characterised by typical motor symptoms (poverty and slowness of movement, rigidity, resting tremor) that are caused by a loss of dopamine (DA)-producing neurons in the substantia nigra, leading to severe DA depletion in the striatum. Post-mortem studies of striatal tissue from PD patients have revealed pronounced morphological alterations in the spiny projection neurons (SPNs), which make up over 90% of the neurons in this structure. The SPN alterations include pruning of dendrites and spines, and a concomitant loss of corticostriatal synapses. In addition, the PD striatum has been found to host glial cells with a pro-inflammatory phenotype. All these pathological features can be recapitulated in rodent models by applying a severe lesion of the nigrostriatal DA pathway.

Specific Aims: Using rodent models of nigrostriatal dopaminergic degeneration, we aim to (i) clarify the relationship between loss of DA input, reactive glial changes, and structural-physiological alterations affecting the SPNs; (ii) dissect the functional significance and key molecular mediators of the above changes. 

Methods: Mouse models of acute and severe nigrostriatal dopaminergic degeneration are obtained by injecting 6-hydroxydopamine (6-OHDA) in the medial forebrain bundle. The lesion is applied to transgenic mice where the two major populations of SPNs are identified by their expression of fluorescent proteins. Dendritic reconstructions and electrophysiological recordings of SPNs are carried out using two-photon laser microscopy combined with patch-clamp recordings. Changes to microglial and astroglial cells are examined using bright-field immunohistochemistry and triple-antigen immunofluorescence; cytokine expression profiles are studies using quantitative real-time PCR.

Results and interim conclusions: Our time course analysis of neuronal and glial changes in the striatum reveals that: (a) SPNs undergo significant dendritic regression between 5 and 28 days after the DA-denervating lesion; (b) this dendritic regression is accompanied by changes in the neurons´ intrinsic excitability; (c) microglial cells show a pronounced but transient activation during the first days post-lesion; (d) this activation coincides with upregulation of caspase-3 and pro-inflammatory cytokines; (e) astrocytes acquire a reactive phenotype during the first days post lesion, and this phenotype is maintained until the longest survival times examined (45 days post lesion). In another study, we show that caspase-3 activation is causally linked with spine pruning and loss corticostriatal synaptic plasticity in SPNs forming the so-called indirect pathway.

Significance: This work provides novel insights into the plastic changes affecting neurons and glial cells following a loss of nigrostriatal DA inputs. In the long-term, this work will lead to an improved understanding of the pathophysiology of PD and thus inform the development of improved treatment strategies.

Filip Bäckström

Time: February 10 2022, 15:00
Title: Translational studies of local and systemic immune reactions in epilepsy and Parkinson’s disease
Main supervisor: Maria Swanberg
Co-supervisor: Christine Ekdahl Clementson
Opponents: Angela Cenci Nilsson, Lena Uller


There is a strong neuroinflammatory component in many neurological disorders, including Parkinson’s disease (PD), epilepsy and autism spectrum disorders (ASD) including glial cell activation and altered cytokine levels. 

Research Question/Method
In my thesis project I investigate local and systemic immune responses in animal models of PD and epilepsy/ASD with the aim of identifying immunomodulatory mechanisms in the respective diseases. 

In the projects focusing on PD, we are using rats with naturally occurring variants in the class II transactivator (Ciita) gene ultimately leading to different levels of major histocompatibility complex II (MHCII). Using a PD model, we show that lower Ciita levels are associated with lower MHCII levels and an increased spread of pathological aggregated protein. We use flow cytometry and ELISA to further characterize local and peripheral immune populations and responses.

In the projects focusing on epilepsy and ASD, we are using Syn2KO mice with epileptic seizures and ASD-like behavior. Syn2KO mice have altered levels of IL-6, synaptic proteins and more activated microglia during epilepsy development. By systemic treatment using an IL-6 receptor antibody we evaluate seizure burden, behavior and neuroinflammatory response in Syn2KO mice. 

Preliminary Results and Significance
In the PD project we find that lower Ciita levels are associated with less MHCII and CD86 in microglial cells whereas the percentage of MHCII+ microglia and circulating myeloid cells are higher in naïve rats. Additionally, less Ciita resulted in trends of higher CD86 levels in circulating myeloid population, a lower CD4/CD8 T lymphocyte ratio but higher levels of TNF-a in serum in naïve rats. Taken together these results indicate that altered Ciita levels have an effect on baseline immune populations which could mediate an increased susceptibility to PD-like pathology.

In the epilepsy/ASD project we show that systemic treatment with an IL-6 receptor antibody (IL6-R ab) in Syn2KO mice could reduce seizure frequency if treatment was initiated before, but not after, seizure debut. We did not observe any reversal of the imbalance in synaptic protein levels and only induce minor changes in microglial activation of Syn2KO mice. Additionally, no changes in social behavior, anxiety, anhedonia, or spatial memory after systemic IL-6R ab treatment were observed.

Published papers
Jimenez-Ferrer I, Backstrom F, Duenas-Rey A, Jewett M, Boza-Serrano A, Luk KC, Deierborg T, Swanberg M. The MHC class II transactivator modulates seeded alpha-synuclein pathology and dopaminergic neurodegeneration in an in vivo rat model of Parkinson's disease. Brain Behav Immun 2021;91: 369-382.

Andreas Bruzelius

Time: Feb 4th, 2022 10:00 AM 


Title: A cell-based disease model for psychiatric disorders using reprogramming technology

Main supervisor: Daniella Rylander Ottosson

Co-supervisors: Malin Parmar

Opponents: Zaal Kokaia, My Andersson


The limited access to human neurons (or nerve cells) in modern science slows down our capacity to understand and study complex neurological disorders and mechanisms. Reprogramming technology has opened up a new path with the means to generate neurons from somatic cells either via induced pluripotent stem cells or via direct reprogramming using defined set of transcription factors, microRNAs, and/or through chemical manipulation. This allows a diverse array of neurons to be derived in vitro from any individual human. These techniques have with time grown more refined and the generation of distinct neural cell types has opened the field for human reprograming-based disease models of neurological disorders that involve specific neuronal cell types.

Research Question/Method
This project aims at investigating different cell reprogramming approaches to generate GABAergic interneurons from somatic cells, such as human skin cell, that could be used to develop a future disease model for neuropsychiatric disorders.

Preliminary Results
In the two published studies we have reprogrammed human adult skin cells and human glia to GABAergic interneurons in vitro. The reprogrammed cells show complex neuronal morphology and are positive for subtype specific interneuron markers such as parvalbumin, calbindin and calretinin. Moreover, the cells exhibit neuronal function and postsynaptic activity indicative of a successful neuronal conversion. We are now exploring a disease model built on the interaction between astrocytes and interneurons deriving from the same individual.

This project looks to overcome the challenge of acquiring human GABAergic interneurons in vitro in a non-invasive manner. GABAergic interneurons have implication in many neurological and neuropsychiatric disorders. Thus, investigating reprogrammed neurons from people afflicted will help us better understand key mechanisms responsible for the pathology and in turn how to better treat them.

Lotte Vanherle

Time: 10th of February 2022, 13.00pm

Zoom link:

Title:  Targeting sphingosine-1-phosphate in cardiovascular disease and target organ damage

Main supervisor: Anja Meissner

Co-supervisor:  Daniel Engelbertsen, Lena Uller, Tomas Deierborg

Opponents: Emma Börgeson and Eva Bengtsson


Cardiovascular disease (CVD) is the leading cause of death and a major risk factor for damage in target organs. Among them, hypertension and heart failure (HF) have been linked to lung complications and to neurodegenerative conditions. Due to the lack of mechanistic understanding of molecular signaling leading to target organ damage (TOD) during CVD, treatment options are sparse.
The bioactive sphingophospholipid sphingosine-1-phosphate (S1P) has gained increasing attention in CVD pathophysiology due to its involvement in both vascular function and immune cell responses. Altered S1P levels have been reported in several cardiovascular and inflammation-associated diseases, including HF, atherosclerosis, stroke, and hypertension.

Research questions
This PhD work aims at (1) investigating molecular mechanisms by which HF affects target organs and testing their targetability; (2) involvement of S1P signaling in hypertension and testing if and how specific targeting of the S1P signaling axis efficiently lowers BP.

Preliminary results
We showed augmented S1P signaling in a mouse model of HF where elevated circulating and tissue levels associate with immune cell infiltration into the lung. Moreover, altered S1P signaling during HF results in augmented cerebrovascular tone resulting in reduced perfusion of the brain with consequences for neuronal structure and memory function. Importantly, we identified a targetable mechanism by showing that the cystic fibrosis transmembrane regulator (CFTR), a critical bottleneck for S1P degradation, is altered in the HF lung and brain. We show that CFTR corrector treatment ameliorates HF-associated pulmonary inflammation and neurodegeneration.

In a human study cohort, we identified that increases in plasma S1P levels associate with increments in blood pressure (BP) and correlate to important inflammation and CVD markers. In line with this, therapeutic inhibition of S1P generation reduces elevated BP in a mouse model of hypertension by modulating the immune system.

Last year, about 18 million people died due to CVD. TOD associated with CVD contributes to this high mortality. Moreover, chronic lung and neurodegenerative diseases can increase disease burden and reduce quality of life and treatment compliance, which can worsen disease outcome. It is therefore crucial to understand the molecular mechanisms underlying TOD in CVD to find new effective treatment options and improve overall disease outcome.

Li Liu

Time: 21st of January 2022 9:00 am

Location: I1341, BMC

Zoom link:

Title: The role of myocardin related transcription factors in transcriptional regulation in smooth muscle

Main supervisor: Karl Swärd

Co-supervisors: Catarina Rippe, Bengt Uvelius, Sebastian Albinsson

Opponents: Isabella Artner, Nils Wierup



Myocardin related transcription factors (MRTFs), including myocardin/MYOCD, MRTF-A/MKL1, and MRTF-B/MKL2, are transcriptional coactivators that form a tetrameric complex with serum response factor (SRF) on DNA elements called CArG-boxes. MRTFs respond to mechanical stimuli and substrate rigidity. Their activation leads to transcription of a subset of SRF target genes that are important for myogenic differentiation and cytoskeletal structure. MRTF-SRF signaling is perturbed in many smooth muscle-related diseases, including neointima formation and atherosclerosis, as well as in gastrointestinal and urogenital maladies. 

Research question / method

This project aims to further investigate the targets of MRTFs, their physiological function, and their potential value for disease treatment. Using RNA-sequencing and bioinformatics, I aim to identify novel MRTF target genes in smooth muscle cells (SMCs) and other cell types. To this end, I perform in vitro and in situ experiments, respectively, to study the relationship between MRTFs and their potential targets, and I use physical and pharmacological interventions to identify potential regulatory mechanisms.

Preliminary results

In the first sub-project, I identify the muscarinic M3 receptor (CHRM3) as a target of MRTFs and SRF in human SMCs in vitro and in the mouse urinary bladder and ileum in vivo. Among the MRTFs, MRTF-B appears to be the strongest trans-activator of CHRM3. Mechanistic studies suggest that YAP-TEAD signaling is necessary but not sufficient for CHRM3 activation. I conclude that YAP-TEAD and MRTF-SRF likely act cooperatively to drive CHRM3 expression.

In the second sub-project, I confirm previous reports showing that MRTFs have a broad anti-inflammatory impact by suppressing numerous cytokines in human coronary artery SMCs. This effect is equal to, or greater, than the effect of dexamethasone. I find that the underlying mechanism of action cannot solely depend on RelA sequestration, as previously suggested, and that SRF is involved in regulation of IL1B and CXCL8. Taken together, this work supports the concept that phenotypic modulation of SMCs involves toggling between contractile and inflammatory phenotypes, in addition to the classical paradigm where SMCs switch between contractile and synthetic phenotypes.

In the third sub-project, we establish NG2/CSPG4, CD146/MCAM and VAP1/AOC3 as MRTF-SRF regulated genes. Furthermore, we demonstrate that MCAM and AOC3 activation by MRTF-A depends on promoter regions containing CArG motifs, and on the epigenetic modifier KDM3A. Finally, these genes respond to changes in actin dynamics and ternary complex factors, and to the MRTF-SRF inhibitor CCG-1423. 


The transcriptional impact of MRTFs may be suited for therapy. Indeed, efforts in drug development aim to target MRTFs to reduce cancer metastasis. Therefore, deeper understanding of the role of MRTFs in transcriptional regulation in health and disease is vital. Such insight may also guide pharmacological development and provide understanding of pathology in smooth muscle-related disease states.


Jiao Dong

Time: 17th of December 10:00am

Location: BMC I:I1345

Zoom link:
Title: Bioengineering and cell-derived strategies for salivary gland regeneration
Main supervisor: Darcy Wagner
Co-supervisors: Sakai Kiyoshi (Nagoya University), Hideharu Hibi (Nagoya University) 
Opponents: Anna-Karin Larsson Callerfelt, Irma Mahmutovic Persson


Background: Salivary gland (SG) hypofunction, clinically characterized as reduced saliva flow, is one complication arising from radiotherapy after oropharyngeal cancer. SG hypofunction can also arise from diseases such as Sjögren's syndrome or develop after maxillofacial surgeries. Due to SG hypofunction, these patients have difficulties in mastication, swallowing and chewing as well as increased risks for dental cavities and mucosal ulcers, which all reduce their quality of life. Conventional treatments include administering radioprotectors, parasympathetic secretagogues, saliva substitutes or other mouth moisturizers. However, their efficacy depends highly on the remaining functional secretion units and mostly provide temporary relief. Therefore, approaches to regenerate salivary glands have attracted interest. While some progress has been made using gene therapy and stem cell-based therapies, they have thus far not been able to completely restore function. Due to new surgical approaches and advances in ex vivo bioengineering of tissue, organ/tissue transplantation has recently emerged as another category of regenerative therapy to restore SG function.
Research Question/Method: In this project, we aim to develop and validate new regenerative medicine approaches for salivary gland regeneration through the use of new biomaterials and cell derived therapies. We aim to derive salivary gland specific biomaterials by decellularizing salivary glands to obtain three-dimensional scaffolds or for use in bioinks. Cultured precision cut salivary slices (PCSS) will serve as a supplemental bioengineered ex vivo model.
Preliminary Results: We have begun optimizing decellularization protocols based on detergent and enzymatic immersion of excised murine salivary glands. We have observed complete removal of cells via histological assessment and have begun characterizing architectural integrity in these scaffolds. We have also evaluated residual DNA both quantitatively and qualitatively with each different decellularization method.We have established techniques to controllably generate PCSS with desired thicknesses ranging between 50-500um PCSS from murine fresh salivary glands with a vibratome. Their architecture and viability was intact over 96 hours of ex vivo culture.
Significance: This study aims to define an optimal decellularization protocol for salivary gland matrix for ex vivo salivary gland regeneration which could provide permanent restoration of SG function in patients with SG hypofunction due to various causes.

Raquel Garza

Time: 14th of October 10:00am

Location: Segerfalk A10, BMC

Zoom link:

Title: The role of transposable elements in the human brain - Studies about neuronal development, adulthood, neurodegeneration and cancer

Main supervisor: Johan Jakobsson

Co-supervisors: Malin Parmar

Opponents:  Helena Persson, Henrik Ahlenius


Transposable elements (TEs) are genetic elements that have invaded our genomes millions of years ago. They make up for almost half of our genome, but are usually silenced via histone modifications and DNA methylation. Most TEs transpose in a copy-paste manner, potentially causing mutations and changes on the epigenome. TEs can also be transcribed as small RNAs, or act as enhancers or promoters. Their virus-like structures can also activate of our immune system. 

Research question/method
 This project aims at investigating the role of TEs in the human brain during development, healthy adulthood, neurodegeneration, and in cancer. Given TEs repetitive nature, these studies have a special focus on how to approach some of the bioinformatical challenges the analysis of TEs entails. To that end, we have developed specialized pipelines to analyse TE expression in bulk and single cell RNA sequencing data. 

Preliminary results
 Trim28 is a well-known protein to be related with the recruitment of histone modifications to silence TEs. In our first study we found that it is critical for the silencing of ERVs during brain development in mice. We found that the absence of this protein during development produces neuroinflamation in adulthood, but that the knock-out of the protein once the animal is adult, is irrelevant for the silencing of these elements. 
In our second project, we investigated the expression of evolutionary young L1s (most common TEs in the human genome) in human brain development and in healthy adulthood. Our analysis demonstrates that evolutionary young full-length L1s, including human-specific L1s (L1HS), are expressed at high level in both the developing and adult human brain. Looking at the different cell types in the embryonic samples, we found that both immature dividing progenitors as well as more mature non-dividing cells express high levels of L1s. During adulthood, we observe a high-level expression of L1s in the different neuronal populations, but not in glial cells.
For our third study, we focused on the expression of transposable elements during disease. We sequenced bulk and single nuclei of biopsies taken from glioblastoma multiforme (GBM). Our preliminary results show that the most affected cells in the biopsies are also those that have the lowest expression of TEs. We hypothesise that the low expression of TEs could be beneficial to the cancerous cells, as a high expression of TEs could activate the immune system. 

These studies attempt to shed light on the role of TEs throughout human life. The implications of human-specific L1s being expressed in the brain raises several questions about the functional consequences of these elements being expressed, intra-individual variations, and of course their role during disease. The understanding of this, as our preliminary results of our cancer project suggest, could have clinical implications.

Frida Berlin

Time: Oct 15, 2021 09:00 AM Stockholm

Location: BMC I1345

Title: Mast Cell-Mediated Orchestration of the Immune Responses in Chronic Respiratory Diseases

Main supervisor: Cecilia Andersson

Co-supervisors: Lena Uller och Ellen Tufvesson

Opponents: Jonas Erjefält,  Hamid Akbarshahi



Mast Cell-Mediated Orchestration of the Immune Responses in Chronic Respiratory Diseases

Chronic respiratory diseases, including asthma and chronic obstructive pulmonary disease (COPD) affects over 300 million people and are the second largest cause of mortality in the world. These diseases are often characterized by airway remodeling and impaired epithelial function. Mast cells (MCs) are known to home into the lung tissue, including the airway epithelium, in these patient groups. It remains less understood if, and what role, MCs have on epithelial cell function in disease pathology of chronic respiratory diseases.

Research questions and method
This project aims at investigating the effect of MC mediators on epithelial barrier properties, with specific focus on epithelial cell remodeling, function and antiviral response. We perform in vitro experiments to study the effect of MC proteases tryptase and chymase on human bronchial epithelial cells (HBECs) at gene, protein and functional levels. Functional studies are primarily assessed using holographic live cell imaging. Also, the effect of proteases on antiviral response in bronchial and alveolar cells are studied using virus associated toll-like receptor (TLR) agonists.

Preliminary results
In the first and published study, we found that both tryptase and chymase significantly alter epithelial cell morphology, proliferation and migration. Also, immunocytochemistry showed a significant rearrangement of the cytoskeleton in treated cells. We have also shown that tryptase increase cell survival properties, both at a functional and at gene (BCL2A1 and BIRC3) levels. Furthermore, our preliminary data shows that epithelial cells treated with tryptase have altered antiviral response, seen as a change in cytokine production and release. 

Respiratory disease pathology is associated with abnormal epithelium and increased MC activity. Despite the high prevalence and mortality worldwide, very little is known regarding the epithelial – mast cell crosstalk. Investigating these interactions will help us to understand the pathology behind the disease development and may lead to better and more specific therapies.

Hannah Åbacka

Time: Oct 5, 2021 10:00 AM Stockholm

Location: Dora Jacobsohn D1513c

Title: Adipocytes in interplay with leukaemia cells and bacterial metabolites

Main supervisor: Karin Lindkvist

Co-supervisors: Olga Göransson, Anna Hagström-Andersson

Opponents: Yvonne Ceder, Johanna Sernevi Säll 


Adipose tissue maintains several vital processes in the body. However, it is also linked to diseases. Both leukaemia and type 2 diabetes are negatively affected by obesity. 

Research question/Method
The first aim is to resolve potential interplay between adipocytes and drug resistance in leukaemia. Here, we study glucose and lipid uptake in Acute myeloid leukaemia (AML) cells and how it is influenced by surrounding adipocytes. By looking at levels of proteins in AML cell lines using microscopy and immunocytochemistry we can discover differences in expression of receptors that can be related to disease. We also investigate how inhibition of these receptors can be used to sensitize leukaemia cells to chemotherapeutic drugs. The second aim is to determine how bacterial metabolites may affect insulin signalling in adipocytes and thus contribute to development of 2 diabetes. By studying the expression of receptors in adipocytes we can understand how the adipocyte is influenced by bacterial metabolites. This is accomplished by determining phosphorylation of proteins involved in insulin signalling and by calcium signalling studies.

Preliminary results
So far, we have seen that inhibition of glucose transporters can make the leukaemia cell more susceptible to chemotherapy in an AML cell line. We have also found that there can be differences in lipid uptake by AML cells due to variances in lipid receptor expression. This can be used for further studies on lipid uptake from adipocytes to leukaemia cells. Investigations on how a bacterial metabolite affect adipocytes have been initiated and has resulted in the production of reporter cell lines expressing receptors for studying calcium flux.

Obesity is a rising global health burden. It can contribute to many health issues and complicate their treatment. This makes the adipocyte and its interaction with other cells in disease an important subject to study. Metabolic differences in AML cells could be aimed at to lower the dose of chemotherapy drugs given to patients. This includes studying how adipocytes affect leukaemia cells. Investigating how adipocytes in turn are affected by metabolites could help improve our knowledge in insulin signalling deficiencies in type 2 diabetes.

Shiva Emami

Time: Sep 30, 2021 09:00 AM Stockholm

Location: Zoom meeting:

Meeting ID: 689 9995 9961

Title: A Recombinant Group A Streptococcus (GAS) Strain Expressing a T Cell Immunodominant Epitope within the M1 Protein Elicits Protective Immunity in Mice Through Induction of an IFN-Dependent Humoral Response.

Main supervisor: Bengt Johansson Lindbom

Co-supervisors: Jenny Persson

Opponents:  Fredrik Carlsson, Mattias Collin


Streptococcus pyogenes or Group A Streptococcus (GAS) is associated with a wide range of infectious diseases in humans and is also responsible for post-infection autoimmune disorders. The M protein represents an important GAS virulence factor, for example providing antiphagocytic functions. The N-terminal domain of the M protein is hypervariable and has served as the target for serological typing of GAS. 

Research question/method
The purpose of this project is to investigate protective immunity against GAS. We used a recombinant GAS-M1 strain with the immunodominant T cell epitope 2W inserted in the N-terminal part of M1 (GAS-2W). Several mice strains were used in our experiments to evaluate the impact of various parts of immune system on protection against GAS.

In the current study, We show that repeated administration of heat-killed GAS of the M1 serotype (GAS-M1) fails to induce protective immunity in C57Bl/6 mice but that mice immunized with a heat-killed recombinant strain (GAS-2W) are protected against wild type GAS-M1. While this protection appeared to rely on T follicular helper (Tfh) cells, and hence a T cell dependent antibody response, immunization with GAS-2W elicited only a moderately increased IgG response to the wt M1 protein and its hyper variable region (HVR) relative to GAS-M1 immunized mice. The IgG2c titer against intact GAS-M1 bacteria was however elevated in the group immunized with the recombinant strain. Consistent with the important role of IFN-g in IgG2c isotype switching, IgG2c responses elicited by GAS-2W were selectively reduced in IFN-g deficient mice and this reduction was associated with loss of protective immunity. Strikingly, total IgG responses were not reduced in the absence of IFN-g and IFN-g deficiency resulted even in enhanced CD4 T cell, TFh cell and germinal center B cells responses after GAS-2W immunization.
Altogether these results indicate that the 2W epitope elicits an IFN-g response that confers protection against wt GAS-M1 through a selective enhancement of antibody responses of the complement-fixing IgG2c subclass.

Katrine Skovgård

Time: 23rd of June at 10:30 am

Location: The halftime review will only be held via Zoom for the public, no audience is allowed at the location, in order for the dissertation to be carried out according to FHM's guidelines. 

Zoom link:

Title: Network dynamics related to motor and neuropsychiatric dysfunction in Parkinson’s disease

Main supervisor: Angela Cenci Nilsson

Co-supervisors: Per Petersson, Pär Halje, Roger Olsson

Opponents:  Daniella Ottosson, Martin Garwicz


Parkinson's disease (PD) is characterised by typical motor features that are caused by severe dopamine (DA) depletion and improved by the DA precursor L-DOPA. However, treatment with L-DOPA gives rise to dyskinesia (abnormal involuntary movements) in a large number of patients. In turn, dyskinesia can be associated with debilitating fluctuations in affective and cognitive functions.

Research question/method
This project aims at investigating network dysfunctions underlying motor and neuropsychiatric impairments associated with PD and L-DOPA-induced dyskinesia (LID). We use severely DA-denervated rats as an experimental model, and several pharmacological tools to manipulate the activity of DA receptors or non-dopaminergic transmitter systems.

Preliminary results
In one study, we present a new clinically relevant model of dyskinesia induced by combined treatment with L-DOPA and the D2/D3 receptor agonist ropinirole. Compared to standard LID models, dyskinesias induced by the combined treatment are found to rely more on the stimulation of D2 than D1 DA receptors, and they respond differently to a range of non-dopaminergic treatments. In a second study, we show that dyskinesias mediated by D1 vs. D2 receptor stimulation are associated with different patterns of LFP oscillations in the cortico-basal ganglia network, suggesting distinct underlying circuit dysfunctions. Treatment with an NMDA receptor antagonist that alleviates dyskinesia induces high-frequency oscillations at 150Hz, a possible neurophysiological marker of a psychotic state. Additional investigations are ongoing.

Our results will shed light on the relative contribution of different DA receptors and non-dopaminergic transmitters to the network dysfunctions associated with PD and LID. In turn, this knowledge will inform the development of precise treatments and neurophysiological biomarkers of drug-altered states in PD.

Megg Garcia

Time: June 18, 9:00 A.M.

Location: The halftime review will only be held via Zoom for the public, no audience is allowed at the location, in order for the dissertation to be carried out according to FHM's guidelines.

Zoom link:

Title: Neuroinflammatory alterations associated with intraneuronal amyloid-β in Alzheimer’s disease

Main supervisors: Tomas Deierborg and Gunnar Gouras

Co-supervisor: Sara Bachiller

Opponents: Agnete Kirkeby and Anna Erlandsson (Uppsala University)



Our current understanding of Alzheimer’s disease (AD) is framed around the amyloid cascade hypothesis. This hypothesis supposes that extracellular amyloid-beta (Aβ) plaques, a hallmark of the disease, triggers downstream events such as intracellular tau aggregation, neuroinflammation and, ultimately, dementia. However, increasing evidence is showing how, even before plaques, neuroinflammatory alterations are occurring in response to less well-known early pathological events. In addition, evidence suggests that microglia may play a role in synaptic loss in AD, which is notable as synaptic loss correlates with cognitive decline. Moreover, before plaques, Aβ has been found to aggregate intraneuronal, and this may play a role in early synaptic dysfunction.

Research question/Method
With synaptic dysfunction and loss as a commonality, we ask whether there is an interaction taking place between neurons and microglia in response to intraneuronal Aβ. To answer this question, we use the 5xFAD mouse model of AD and look at neurons and microglia in young, 6-week-old mice. 5xFAD mice overexpress human amyloid precursor protein and presenilin-1 with genetic mutations that are known to cause early-onset AD. The result is mice that develop Aβ plaque pathology by 8 weeks of age. Using these mice, we will use immunohistochemistry to characterize the changes that are occurring in two connected brain regions in young 5xFAD mice: the subiculum and mammillary bodies. Both the subiculum and mammillary bodies display high levels of intraneuronal Aβ at 6 weeks of age. Pyramidal neurons of the subiculum project to and terminate in the mammillary bodies, among other places, making this system a useful model to study somatodendritic versus axonal Aβ.

Preliminary results
We find highly aggregated intraneuronal Aβ in the subiculum and mammillary bodies of 6-week-old 5xFAD mice. Though the Aβ aggregates resemble early plaques, typical markers of plaque-reactive microglia are not yet upregulated, and further investigation is needed to determine whether other neuroinflammatory alterations are occurring.

Alzheimer’s disease is the most common cause of dementia and can only be treated symptomatically as there are no treatments that affect the progression of the disease. Understanding the mechanisms that occur early in the disease may help in the development of a treatment.

Cecilia Skoug

Time: June 2nd, 2021 14:00

Location: The halftime review will only be held via Zoom for the public, no audience is allowed at the location, in order for the dissertation to be carried out according to FHM's guidelines. 
Zoom link:
Title: Bioactive lipids as neuroprotective targets in type 2 diabetes
Main supervisor: João Duarte
Co-supervisor: Cecilia Holm
Opponents: Malin Fex and Gesine Paul-Visse


Metabolic syndrome components, obesity and type 2 diabetes (T2D) impact the brain through a process that involves synaptic dysfunction. The brain is rich in the variety of lipids with bioactive roles such as sphingolipids, endocannabinoids, eicosanoids and cholesterol. Metabolism of these lipids and their signaling pathways are putative targets  to afford neuroprotection. Hormone-sensitive lipase (HSL) is a regulatory enzyme of lipolysis in the adipose tissue. In the brain, which relies mainly on glucose oxidation, we propose that HSL regulates the availability of bioactive lipids for fine tuning of neuronal function. On another hand, sphingosine 1-phosphate (S1P) acts on a family of metabotropic receptors that might modulate neuronal activity.

Research questions
We investigate the cellular distribution of HSL and S1P receptors in the brain, explore novel roles of brain HSL, and test the ability of S1P receptors to control neuron physiology, and their alterations in models of T2D. With this work, we aim at identifying targets for synaptic protection in T2D.

Preliminary results
HSL is active across the whole brain, is located in synapses, and has a homeostatic role in maintaining pools of lipids needed for brain function. All five S1P receptors are also located in synapses of the mouse cortex, and have the ability to modulate neuron firing in vitro

Our puropose is to develop a strategy to halt brain dysfunction in metabolic disorders, namely T2D, by modulating lipid metabolism and signaling.

Edoardo Brandi

Time: May 28, 2021 01:00 PM

Location: The halftime review will only be held via Zoom for the public, no audience is allowed at the location, in order for the dissertation to be carried out according to FHM's guidelines. 

Zoom link:

Title: Role of Neuroinflammation in Parkinson’s disease and Related Disorders

Main supervisor: Jia-Yi Li 

Co-supervisor: Gunnar Gouras

Opponents: Tomas Deierborg, Professor and Karsten Ruscher, PhD



Microglia represents the macrophage population in the central nervous system (CNS) and represents the first line of immune defense. Recent studies show that microglia appears highly heterogeneous in the CNS in terms of morphology, cell density, transcriptome and expression of different inflammatory mediators. Microglial heterogeneity may strongly influence the preferential involvement of different brain regions in several neurodegenerative diseases. Synucleinopathies are neurodegenerative disorders characterized by intracellular inclusions called Lewy bodies (LBs), in which a-synuclein (a-syn) is the primary protein component. Available evidence implies that different aggregated stains of a-syn can stimulate an inflammatory reaction, suggesting that a-syn oligomers or higher species may trigger the inflammatory responses Activated microglia can reversely induce a-syn post-translational modifications (PTMs) and modify the conformation and characteristics of the protein.

Aims and methods
Firstly, we evaluate whether microglial heterogeneity may lead to a different inflammatory response in different brain regions. In order to study this aspect we induce a systemic inflammatory reaction in CX3CR1+/GFP mice through an intraperitoneal injection of lypopolysaccarides (LPS), dose-dependently and time-dependently. The inflammatory responses are assessed in 15 different brain regions. 

Secondly, we investigate whether and how microglia is able to induce a-syn PTMs and whether these modifications can lead to form aggregates or toxic species. In order to study these aspects we generate several microglial (BV2) cell lines that stably express differently mutated a-syn and we characterize them in the naïve (control) condition and also under a-syn preformed fibrils (PFFs) and/or LPS stimulation. 

Preliminary results
We have observed clear region-specific neuroinflammatory responses in presence of systemic inflammation. Particularly, it appears that the substantia nigra pars reticulata (SNpr) is most sensitive compared with other brain regions, implying the high susceptibility of SNpr to neuroinflammatory attacks. In addition, we have observed a high BV2 capacity to release and uptake vesicles enriched with a-syn and to form toxic aggregates under exposure of a-syn PFFs.

Understanding the impact of neuroinflammation on neurodegeneration and a-syn PTMs formation in different synucleinopathies may help us to better understand these pathologies. Thorough analyses of microglia heterogeneity may help identify specific neuroinflammatory pathways and specific pharmacological targets for future treatments.

Laura Torres-Garcia

Time: May 27, 2021 10:00 AM

Location: The halftime review will only be held via Zoom for the public, no audience is allowed at the location, in order for the dissertation to be carried out according to FHM's guidelines.

Zoom link:

Title: Bridging the Gap between Alzheimer’s and Parkinson’s Disease

Main supervisors: Gunnar Gouras and Jiayi Li

Co-supervisor: Antonio Boza-Serrano

Opponents: Per Petersson, PhD and Prof. Niklas Marklund, Professor




Alzheimer’s disease (AD) is the major cause of dementia, while Parkinson’s disease (PD) is the most common movement disorder. AD and PD are both characterized by the pathological accumulation and aggregation of amyloidogenic proteins, α-synuclein (aSyn) in PD, and amyloid-β (Aβ) and Tau in AD. Genetics links Tau with both diseases; the microtubule-associated protein Tau (MAPT) gene is a major risk factor in PD, and the H1 haplotype of MAPT increases the risk of developing AD and PD. However, the role of Tau in these diseases remains unclear. Both Aβ and aSyn can induce Tau pathology, while aSyn has also been shown to interact with Tau in vitro. Co-occurrence of aSyn- and Tau-containing inclusions occurs in a variety of neurodegenerative diseases. However, how amyloidogenic proteins interact and/or influence each other and enhance neurodegeneration is still poorly understood. We aim to elucidate the relationship between Tau and Aβ and Tau and aSyn in the pathophysiology of AD and PD. 

Research question/Method
The main focus of the PhD is to evaluate effects of the interaction between Tau-Aβ and Tau-aSyn in AD and PD. We aim to elucidate how the interaction between aSyn and Tau takes place; using a Bimolecular Fluorescence Complementation (BiFC) approach, we intent to visualize direct interaction between the proteins in a biologically relevant context. On the other hand, we want to understand how Tau influences neuronal excitability in the context of AD, for which calcium imaging in primary neuronal cultures of an AD mouse model (APP/PS1) is used.

Preliminary results
We have observed that aSyn and Tau interact with each other in cellular and animal models. In addition, we see that Tau seems to have a significant impact on neuronal excitability. 

Understanding the direct or indirect interactions between Tau-Aβ and Tau-aSyn could help to understand the pathological and physiological consequences of these interactions in AD and PD, and can facilitate the development and/or screening of potential drugs/mechanisms that could modulate these interactions.

Matilde Negrini

Time: 11th of June at 9:00 am

Location: The halftime review will only be held via Zoom for the public, no audience is allowed at the location, in order for the dissertation to be carried out according to FHM's guidelines.

Zoom link:

Title: Cognitive deficits in a preclinical rodent model of Parkinson's disease

Main supervisor: Andreas Heuer

Co-supervisor: Marcus Davidsson, Tomas Björklund

Opponents: Marco Ledri, Tomas Deierborg


Currently the most used preclinical animal models of Parkinson’s Disease (PD) utilise either neurotoxins (e.g. 6-OHDA) or overexpression of alpha-synuclein (αSyn). The former neurotoxin-based model is an end-stage model of PD and does neither display the progressive nature of the disease nor the additional protein inclusions seen in cortical and subcortical structures. The latter, αSyn overexpression, does recapitulate the progressive nature of the disease that is seen in human patients and can be achieved by using either transgenic animal lines or viral vector overexpression models. Adeno-associated viral (AAV) vectors have proven to be a promising tool to induce the desired pathological features, such as αSyn-linked pathology and progressive cell loss. Moreover, to produce more robust and reproducible PD pathology, recent studies have combined viral vector-based overexpression of human wild-type alpha-synuclein (αSyn) with the delayed or simultaneous inoculation of preformed fibrils (PFFs). However, the results from AAV-based studies published so far are heterogeneous. Furthermore, despite non-motor impairment seen in PD patients have recently been recognised as main drivers in the reduction of patients’ quality of life, current animal models are either not addressing these or are not being able to model them appropriately.

Research questions
The main focus of the project is to generate, validate, and characterise a stable and reproducible AAV-αSyn overexpression rat model of PD with a focus on non-motor symptoms.

Preliminary Results
We observed reduction of TH expression and loss of neurons in the midbrain in all AAV-αSyn-injected groups, with or without additional PFFs inoculation. The overexpression of αSyn alone, induced stable motor deficits and dysfunctional dopamine release/reuptake in electrochemical recordings in the ipsilateral striatum. Interestingly, we observed a substantial formation of insoluble αSyn aggregates and inflammatory response only when PFFs and AAV-αSyn were combined.

Animal models which do only model certain aspects of a disease make the progression towards clinical trials problematic therefore it is imperative to develop relevant animal models with higher reproducibility and face-validity to develop and assess therapeutic interventions as well as to understand the molecular mechanisms underlying PD pathology.

Ida Jeremiasen

Time: Friday June 4th 2021. Please note that only the opponents can attend physically.

Location: Conference room 2, Seminariet, SUS, Lund (The halftime review will only be held via Zoom for the public, no audience is allowed at the location, in order for the dissertation to be carried out according to FHM's guidelines.)

Zoom link:

Title: Pulmonary hypertension in children - vasodilator therapy and novel imaging

Main supervisor: Docent Karin Tran-Lundmark, Lund University

Co-supervisors: Docent Estelle Naumburg, Umeå University

Opponents: Docent Valéria Perez de Sá, Lund University and Professor David Ley, Lund University


Pulmonary hypertension (PH) is associated with significant morbidity and mortality. Pulmonary vasodilator therapy has been shown to reduce pulmonary vascular resistance and alleviate symptoms. {Simonneau, 2014 #223}Strategies for therapy in children have so far mainly been off-label and based on adult trials and experience. Additional data on safety and efficacy of pulmonary vasodilators in children is needed, as well as data on the mechanisms behind vascular remodeling in different groups of PH and group specific treatment effects.

-to assess effects of pulmonary vasodilator therapy in children with PH associated with complex congenital heart defects

-to evaluate the national and regional use of pulmonary vasodilator therapy in the Swedish paediatric population and

-to analyse the vascular changes in PH using synchrotron-based phase contrast micro-CT.

Methods and preliminary results
Study I is a retrospective case notes review of children with single ventricle physiology, treated with pulmonary vasodilators by the UK Pulmonary Hypertension Service for Children 2004-2017. Pulmonary vasodilator therapy was found to be well tolerated and associated with improvements in saturation and mean pulmonary arterial pressure in this group of patients. It appeared safe to discontinue when no clear benefit was observed.

Study II and III are register-based studies of prescriptions of pulmonary vasodilators to Swedish children, below seven years of age at treatment initiation, between 2007-2017.

For study II, the focus was to assess overall patient characteristics and strategies for pulmonary vasodilator therapy. Patients with PH associated with congenital heart disease or bronchopulmonary dysplasia were most commonly prescribed pulmonary vasodilator therapy.  Monotherapy was common and pediatric prescriptions of sildenafil increased during the study period. Despite treatment, mortality was high.

Study III will focus on the subgroup of prematurely born children who suffer from PH. Data collection is ongoing.

Study IV is a combination of synchrotron-based phase contrast micro-CT scanning and retrospective case notes review of patients with pulmonary veno-occlusive disease to evaluate vascular changes. Data collection is ongoing.

Our goal is to improve quality of life and survival in pediatric PH by studying pathophysiological mechanisms, treatment characteristics and effects of pulmonary vasodilators in different subgroups.

Published and submitted manuscripts
I: Jeremiasen I, Tran-Lundmark K, Idris N, Tran P-K, Moledina S. Pulmonary vasodilator therapy in children with single ventricle physiology; effects on saturation and pulmonary arterial pressure.

Published in Pediatric Cardiology July, 2020

II: Jeremiasen I, Naumburg E, Westöö C, Weismann C, Tran-Lundmark K. Vasodilator therapy for pulmonary hypertension in children: a national study of patient characteristics and current treatment strategies

Submitted manuscript April, 2021

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Oscar Manouchehrian

Time: Thursday the 15th of April at 10.00

Zoom link

Main supervisor: Tomas Deierborg

Co-supervisors: Iben Lundgaard, Fredrik von Kieseritzky and Sara Bachiller

Opponents: Hanne Birgit Gredal and Johan Andersson


According to the WHO, 50 million people are affected by dementias, and with aging populations, these numbers are expected to increase. Alzheimer’s disease (AD) is the most common form of dementia, followed by vascular dementia (VaD). One is believed to be caused by abnormal accumulation of certain protein aggregates, the other one by impaired blood flow to the brain, but the two also share neuroinflammatory components. Recommended preventative measures for both AD and VaD include cognitive stimuli, healthy diets and regular physical activity. However, the exact mechanisms of exercise as attenuation in these common diseases remain to be elucidated. In project I, we studied long term voluntary running in a mouse model of familial AD, and in project III, we trained mice on treadmills for a month before subjecting them to a model of hypertension-induced cognitive dysfunction.

Furthermore, in patients with small vessel disease (leading cause of VaD), enlarged perivascular spaces can be seen with MRI. These spaces are believed to play an important role in cerebral waste clearance, through the so-called the glymphatic system, where cerebrospinal fluid (CSF) flushes through the brain at night. It has been speculated that the perivascular spaces are enlarged when harmful residues are accumulated, generating a dysfunctional and inflammatory environment, which in turn causes defective glymphatic function, hypoxia and tissue damage. Whether this theory is true remains to be seen. In project II we have tested a hypothesis whether inflammation can affect the flow of CSF, a piece of the puzzle in this serious story.

The projects in this thesis aim to increase understanding for how exercise can affect murine models of neurodegenerative diseases and will also study the effect of inflammation on CSF-movement.

Martino Avallone

Time: Friday the 23rd of April at 9.00 

Zoom link: 

Title: Precision mapping of molecular changes in Parkinson's disease using gene editing, molecular barcodes and engineered viral vectors 

Main supervisor: Tomas Björklund

Co-supervisors: Malin Åkerblom and Luis Quintino

Opponents: Tomas Deierborg and Marco Ledri


Parkinson's disease (PD) is the second most common neurodegenerative disease affecting over six million people worldwide. It is often classified as a motor disorder, although it has complex pathology comprising many cognitive aspects. The motor symptoms are due to the cell loss of dopaminergic neurons in the midbrain. In a healthy brain, these neurons release dopamine (DA), a neurotransmitter that is key in regulating the basal ganglia circuitry.

A lot of research still needs to be done to answer those questions. In this halftime report, I will describe what has been achieved in the lab during the past two years. The first project aims to establish a rat model of PD based on viral injection protocol that will be available and reproducible between labs worldwide. The second and third projects focus on a single-cell resolution transcriptome readout of dopaminergic neurons from the substantia nigra in the rat and mouse PD model. With these studies, we will for the first time be able to link the molecular changes happening at the beginning to those during the disease progression. The fourth project goal is to study the Arc functional biology in a mammalian brain. The hypothesis is that this protein can be transported between cells regulating their activity. Unraveling this mechanism, we could better understand how brain circuitries are structured. Taken together, these results will deepen our knowledge in the PD field.

Claes Fryklund

Time: April 20th, at 09.00
Zoom link: 
Title: Fat-depot specific differences during onset of adipocyte dysregulation
Main supervisor: Karin Stenkula
Co-supervisor: Karl Swärd
Opponents: Magnus Hillman and Ola Hansson


Fat-depot specific differences during onset of adipocyte dysregulation

Obesity is one of the main risk factors behind insulin resistance and type 2 diabetes (T2D). These conditions are increasing world-wide at an alarming rate, almost tripling in the past 40 years. To accommodate surplus energy, the adipose tissue expands both by increasing the number of fat cells (hyperplasia) and the size of maturated fat cell (hypertrophy). Specifically, hypertrophic adipocytes are associated with impaired insulin response, increased circulating fatty acid levels and ectopic lipid deposition, all factors contributing to onset of T2D. It is known that visceral upper body fat, rather than subcutaneous lower body fat, is a risk factor for T2D. Still, the molecular level behind adipocyte dysfunction, how it is linked to systemic insulin resistance, and if there are adipose depot-specific mechanisms, are yet not resolved.

Research question/method
My project examines the initial changes associated with dysregulated adipose tissue by using short term diet interventions in mice, with specific focus on the caveolae associated protein EHD2. We focus on differences in visceral and subcutaneous fat tissue by looking at adipocyte expansion, insulin sensitivity, and lipid metabolism and trafficking. For that, we have established a global EHD2 knockout mouse model, which serves as a valuable tool to determine the importance of EHD2 in primary mouse adipocytes maturated in vivo.

Preliminary results
So far, we have found fat-depot specific differences in insulin sensitivity following intervention with both high sucrose and high fat diets. Further, ablation of the caveolae-associated protein EHD2 influences visceral fat depot expansion as well as insulin sensitivity and lipolytic rate in subcutaneous adipocytes.

The project provides further knowledge of mechanisms underlying impaired adipocyte function in the hypertrophic state, which contributes to development of insulin resistance and T2D. Further, our studies emphasize fat depot differences in insulin sensitivity and adipocyte function following diet interventions, highlighting that insulin resistant adipocytes might emerge in different ways in different fat depots.

Agnes Agnieszka Paulus

Time: March 26, 2021, at 13.00

Place: Welcome via Zoom link below

Title: Investigation of structural changes in cellular models of pure and mixed proteinopathies.

Main supervisor: Oxana Klementieva

Co-supervisors: Tomas Deierborg, Gunnar Gouras, Oskar Hansson

Opponents: Daniella Ottosson and Michiel Op de Beeck

Zoom link


Alzheimer's disease is a terminal disease characterized by the formation of amyloid aggregates, the so-called amyloid oligomers. These oligomers are characterized by β-sheet structures and are thought to be neurotoxic. However, which of the secondary structures of amyloid oligomers contributes most to the neurotoxicity is unknown. This lack of knowledge exists mainly because it is incredibly challenging to characterize the secondary structures of amyloid proteins in cells. To investigate molecular changes in proteins directly in cells, we used synchrotron-based infrared microspectroscopy, a label-free and non-destructive technique available for in situ molecular imaging to register structural changes of proteins and lipids.

Research questions
The main focus of the project is to evaluate the potential of using infrared microspectroscopy to evaluated the formation of β-sheet structures in cellular models using both pure and mixed cellular models of amyloid aggregation related to Alzheimer's disease.

Preliminary Results
We report the possibility of discriminating different amyloid signatures directly in cells using infrared microspectroscopy and demonstrate that bigenic APP/αSyn and APP/Tau neuron-like cells display changes in β-sheet load. Altogether, our findings support the notion that not a common but rather different molecular mechanisms of amyloid aggregation can be triggered by the cellular environment and, therefore, various mechanisms lead to the development of Alzheimer's disease.

Fredrik Nilsson

Time: March 15, 2021 at 13.00

Place: Welcome via Zoom link below

Title: Evaluating the use of autologous cells for cell-based replacement therapy in Parkinson’s Disease

Main supervisor: Malin Parmar

Co-supervisor: Johan Jakobsson and Deidre Hoban

Opponents: Jia-Yi Li and Isaac Canals

Zoom link:



Parkinson’s disease (PD), the most common neurodegenerative movement disorder, affects approximately 1% of people over the age of 60. Due to mechanisms that are still insufficiently understood, the degeneration of dopaminergic neurons in the substantia nigra pars compacta leads to resting tremor, bradykinesia, and gait and balance deficits. The main pathological hallmark of PD is the presence of Lewy bodies and Lewy neurites, insoluble intraneuronal aggregates made up of misfolded protein. The major component of both Lewy bodies and Lewy neurites is alpha synuclein (a-syn).

Research questions 
The main focus of the project is to evaluate the potential of using patient-specific cells for cell-replacement therapy in PD with focus on if the patient-derived cells acquire disease related pathology. If so, gene-editing presents a viable solution for patients with known genetic mutations, but this approach is not applicable for the majority of PD patients, since 90% of all cases is sporadic. Instead, for sporadic patient lines, a strategy to prevent disease-associated pathology would be to knock out the a-syn gene completely. While this could make the cells immune to developing pathology, it needs to be shown that its deletion will not interfere with the differentiation, maturation, integration, and functional properties of these cells. 

Preliminary Results
So far, we have shown that transplanting an iPSC line from a patient harbouring a triplication of the alpha synuclein gene was able to mediate motor recovery in a rat PD model. However, the grafted cells developed pathological a-syn inclusions over time. Also, using multiple a-syn knockout clones we have shown that they can differentiate and mature into dopaminergic neurons on par with wildtype human embryonic stem cells.

This project will be of great importance to further understand the physiological role of alpha synuclein in the development and function of dopaminergic neurons. Moreover, it will help to determine if knocking this gene out could be of clinical benefit for patients suffering from PD and other synucleinopathies.

Zackarias Söderlund

Date and time: 2021-03-19, 10:00

Location: Online (see Zoom link below)

Zoom link:   Meeting ID: 630 9221 9332

Title: Developing a cell-instructive material for distal lung regeneration

Main supervisor: Gunilla Westergren-Thorsson

Co-supervisor: Emil Tykesson, Linda Elowsson Rendin

Opponents: Anders Aspberg, Deepak Raina


Chronic obstructive pulmonary disease (COPD) is responsible for over three million deaths each year. End stage COPD is characterized by the degradation of lung tissue which severely impairs the gas exchange that occurs in the distal parts of the lung, causing difficulties in breathing and ultimately death. 

Research question and methods
By developing a macroporous lung scaffold mimicking the distal parts of the lung, we aim to replace lost tissue and trigger a healthy regeneration. To recreate the structure of the extracellular matrix (ECM), an elastin-like recombinamer (ELR) consisting of repeated elastin sequences together with cell attachment motifs is used. Growth factors are added to the material to induce cell migration, proliferation and differentiation into functional lung tissue. To reach a specific and controllable release of growth factors, recombinant glycosaminoglycans (GAGs) are utilized. Through microarray screening, the strongest growth factor-GAG interactions are identified, and its association (Kon) and dissociation (Koff) rates are further investigated using surface plasmon resonance (SPR). 

Preliminary results
A macroporous cryogel was constructed by adding ice crystals of different diameters to the ELR. The resulting pore size of the cryogel ranged from 100-1000 µm, compared to the alveolar size ranging from 200-500 µm. The elasticity and stiffness of the cryogel were shown to be independent of the pore size. Through microarray screening, recombinant GAGs with strong binding capacity to multiple growth factors, including VEGF, FGF2 and HGF, were identified. SPR analysis demonstrated large differences in Kon and Koff between these GAGs. By using GAGs with low Koff values, we were able to differentiate HUVECs in vitro, and to steer the immune response when the cryogel was implanted subcutaneously in vivo. SignificanceThe developed macroporous cryogel was shown to have similar structural properties as the naïve ECM of the lung. The identification and characterization of divergent interactions between recombinant GAGs and growth factors could pave the way for fine-tuning the release of growth factors, in order to initiate and steer the subsequent regenerative process. Taken together, these findings provide a promising solution for constructing a cell-instructive material that could ultimately restore distal lung tissue in COPD patients. 

Niloofar Nayeri

Time: Wednesday 17th March 2021, kl. 09:00

Title: Structure-function studies of copper flux across cellular membranes

Main supervisor: Pontus Gourdon, PhD

Co-supervisor: Prof. Karin Lindkvist

Opponents: Derek Logan, senior lecturer, Emil Tykesson, PhD

Zoom link:


Transition metal ions such as iron, copper, and zinc are essential elements required for the survival of all organisms, and yet elevated levels of these metals are highly toxic. Through different regulatory mechanisms, cells ensure that homeostasis is maintained, and ion channels and transporters are critical in this process. Indeed, malfunction of these proteins is associated with severe physiological effects. A precise understanding of such ion transport events across cellular membranes requires insight into the protein structure of the associated, information that will also be valuable for applied sciences.

Research question
This doctoral study aims to dissect the determinants and molecular principles that orchestrate copper passage across inner and outer membranes, deciphering at molecular detail how copper traverse the membrane proteins from one side to the other. The intention is that this will provide fundamentally new insight into not only the molecular mechanisms of these proteins, but also their molecular context and physiological roles. Thereby, the generated data may also pave the way for subsequent drug discovery efforts.

Preliminary results
Herein, I summarize our structural characterization efforts on a range of heavy metal transfer proteins, originating from both human as well as pathogenic bacteria and fungi. The targets were produced to high yields and extracted in detergent solution and purification strategies devised. A high-resolution structure was determined for one of the proteins and well-diffracting crystals were recovered for a related target. Furthermore, two separate functional assays have been developed, overcoming the well-established difficulties with assessment of transmembrane flux of copper.

This work has already provided critically new light on the architecture and molecular function of a specific family of bacterial copper-conducing outer membrane proteins. Moreover, I expect that another structure of a related outer membrane protein soon will be recovered. The work also provides a framework for downstream more in-depth studies of all the copper homeostats proteins that have been approached during my PhD. As copper is exploited both as a biocide and as an antimicrobial agent in medicine, the generated knowledge may open new avenues for generation of novel inhibitors to combat life-threatening infections.

Victoria Ptasinski

Time: Friday 26th Feb 2021, 11:30
Location: The halftime review will only be held via Zoom for the public, no audience is allowed at the location, in order for the dissertation to be carried out according to FHM's guidelines
Zoom link:
itle: Alveolar Progenitor Cells in Lung Damage and Regeneration
Main supervisor: Darcy Wagner, PhD
Co-supervisor: Prof. Gunilla Westergren-Thorsson, PhD
Opponents: Agnete Kirkeby, PhD, Hamid Akbarshahi, PhD


Idiopathic pulmonary fibrosis (IPF) is a chronic respiratory disease characterised by epithelial injury, dysregulated epithelial repair and excessive deposition of extracellular matrix. IPF is assumed to arise from repeatedly failed alveolar epithelial regeneration. The most widely used pre-clinical model of IPF is the in vivo bleomycin model of fibrosis, although it only recapitulates some aspects of progressive human IPF and self-resolves after a couple of weeks. Access to models focusing on alveolar epithelial injury in IPF is limited because of the restricted access to primary alveolar epithelial cells and their limited lifespan in culture. 

Research question
The aim of this doctoral project is to identify dysregulated alveolar stem cell populations and pathways in the epithelium which are amenable to pharmaceutical intervention. Initially, we focused on optimising in vitro and in vivo models which can be used for modeling alveolar epithelial injury in IPF and evaluating the effects of potential anti-fibrotic compounds. We will utilise these models in combination with single-cell sequencing techniques to identify and pharmacologically modulate aberrantly activated alveolar stem cell populations. 

Preliminary results
We have developed an in vitro model of alveolar epithelial injury in IPF using alveolar epithelial organoids derived from human induced pluripotent stem cells. Treatment of these organoids with a cocktail of pro-fibrotic and inflammatory cytokines to mimic the inflammatory milieu in IPF were found to induce changes mimicking several hallmarks of clinical disease, including epithelial injury and reprogramming, aberrant production of extracellular matrix and induction of cellular senescence-associated markers. For in vivo experiments, we have optimised a dosing strategy for a repetitive bleomycin-induced model of pulmonary fibrosis, which is meant to model epithelial injury in chronic pulmonary fibrosis more applicable to human IPF than the currently used single bleomycin model. 

Understanding the aberrantly activated epithelial cell populations and pathways which have become dysregulated in IPF and identifying mechanisms which can activate repair and restoration of normal epithelium may lead to new therapies.

Kajsa Brolin 

Title: Genetic and environmental risk factors behind monogenic and idiopathic forms of Parkinson’s disease
Date and time: 2021-03-02, 10:00
Location: Online (see Zoom link below)
Zoom link: (Meeting ID: 657 3771 3184)
Main supervisor: Maria Swanberg
Co-supervisor: Andreas Puschmann
Opponents: Karin Engström & Niklas Mattsson-Carlgren


Background and methods
Parkinson’s disease (PD) can be categorized into monogenic and idiopathic PD based on the contribution of genetics to disease risk. Monogenic PD is caused by rare DNA variants with large effect sizes. In idiopathic PD, variants with smaller effect sizes in combination with environmental exposures determine an individual’s risk. To date, 90 risk variants have been identified to be associated with idiopathic PD. These explain 16-36% of the heritable PD risk, indicating the presence of additional unknown genetic variants of great importance to the overall disease risk. Risk factors can be more or less specific to a population depending on population-specific genetic architecture, local lifestyle habits and environmental exposures. Therefore, it is essential to study disease etiology both at a local, regional and global scale. We aimed to investigate the contribution of genetics and environmental factors to PD in Sweden, a country often perceived as relatively homogenous when it comes to population structure. The frequency of autosomal dominant mutations was investigated in a national multi-center study and genetic risk variants were investigated in the southern Swedish case-control cohort Multipark’s biobank sample collection (MPBC). Additionally, whole-genome sequencing data from larger European PD cohorts was analyzed in a collaborative project.

Preliminary results
Autosomal dominant mutations were only observed in 0.59% of the investigated patients. Our comprehensive characterization of MPBC revealed associations between PD and multiple environmental factors such as coffee, tobacco and pesticide exposure. We also identified a novel genome-wide significant variant associated with PD that has not been reported previously. In a collaborative project, rare variants in the gene RIC3, which previously had been reported to be associated with PD, were investigated in large European cohorts in which no associations were observed.

Our studies contribute to the understanding of population-specific environmental and genetic risk factors in PD. By investigating populations at a local scale and subsequently bringing data from various populations together, important insights about the biological processes in PD pathology and etiology can be generated, which is substantial for the development of novel treatments.

Roberta Battistella 

Title: Glymphatic function in Parkinson´s disease
Date and time: February 19th, 2021, 9:00
Location: Online (see Zoom link below)
Zoom link: (Meeting ID: 645 9924 1167)
Main supervisor: Iben Lundgaard
Co-supervisor: Angela Cenci-Nilsson
Opponents: Tomas Björklund & Anders Wittrup 


The discovery of the glymphatic system opened a door to a new way of looking at neurodegenerative diseases. Glymphatic system is involved in the clearance of solutes and peptides from the brain through the exchange of cerebrospinal fluid (CSF) and interstitial fluid which is mediated by the water channel aquaporin 4 (AQP4). Interestingly, glymphatic system is impaired in Alzheimer´s disease, and is involved in the clearance of amyloid beta (Ab) from the brain. Despite the evidences that it is involved in AD pathogenesis, glymphatic system´s function in PD and its role in the removal from the brain of a-synuclein, a protein known to aggregate in the brain of PD patients, has not been established yet.

Research question
The aim of this project is to optimise and develop methods to study glymphatic system, and to use them to unveil its role in PD pathogenesis.

To study AQP4 polarization at the astrocytic vascular endfeet in PD models, a method for lectin labelling of blood vessels was optimised, showing that Lycopersicum esculentum agglutinin gives the best specificity and sensitivity in histological stainings. I also demonstrated that glymphatic function is unaltered in AQP4-ASOs-injected mice, despite a ~50% knockdown of aqp4 mRNA persisting up to 4 weeks.The analysis of CSF tracer distribution in mouse models of PD (6-OHDA and human-a-synuclein/pre-formed fibrils, h-a-syn-PFF) showed a trend towards decreased glymphatic influx and efflux of CSF tracer to different tissues. Furthermore, 24hours after intra-striatal injection, h-a-syn-PFFs were found in cervical lymph nodes and nasal mucosa of injected mice, suggesting that the glymphatic system is involved in the clearance of a-synuclein from the brain.

Taken together, these results support the hypothesis that the impairment of glymphatic function, for example induced by aging, can lead to a-synuclein accumulation in the brain, and to the neuronal loss typical of PD, underlying its pivotal role in PD pathogenesis. It is therefore of vital importance to develop methodologies and techniques for glymphatic manipulations to better understand glymphatic system involvement in the pathogenesis of neurodegenerative diseases, as well as to provide alternative treatments to slow down their progression.

Marta Ramos

Time: 2021-03-02, 11:00
Place:  D1513c Dora Jacobsohn, BMC, Sölvegatan 17, Lund. Please note that only the student and supervisor may attend physically.
Zoom link: LU Zoom meeting:  Meeting ID: 633 5186 2806
Title: The role of cerebrospinal fluid dynamics in neuroinflammation
Main supervisor: Iben Lundgaard
Co-supervisor: Thomas Bäckström, Antonio Boza Serrano, William Agace
Opponents: Katharina Lahl, Eskil Elmér


In the past years, the glia-lymphatic (glymphatic) system was discovered and emerged as a player in the removal of interstitial solutes from the central nervous system (CNS). The glymphatic system serves to relieve the brain of solutes from the interstitial space using cerebrospinal fluid (CSF) driven into peri-arterial pathways. Aging, brain injury and neuroinflammation, are associated with persistent reactive gliosis, which may impair glymphatic pathway function. However, not much is known about the role of the glymphatic system in neuroinflammation.

Overall aim of the PhD thesis
This PhD thesis aims to gain an understanding of how neuroinflammation affects CSF transport in the CNS. The role of the glymphatic system is explored in different rodent models of neuroinflammation with especial emphasis on the EAE model of multiple sclerosis.

Results To investigate the effect of inflammation on the glymphatic system, we used LPS-injections to elicit an inflammatory response in mice (project I). We found that LPS treatment impaired perivascular CSF flow and penetration into the brain parenchyma. The decrease in CSF transport was only paired with an elevation in cortical Iba1+ area and an increase in heart rate. In project II, using a rat model of S. pneumoniae meningitis, we found that CSF drainage from the brain to lymph nodes was reduced. Interestingly, degrading neutrophil extracellular traps using DNase I treatment restored glymphatic transport and eliminated edema in rats with bacterial meningitis. In order to study the role of neuroinflammation in more detail, in project III we use an animal model of multiple sclerosis (MS) which is the prototypical inflammatory disease of the CNS. Most of the current knowledge about neuroinflammation has been obtained from the experimental autoimmune encephalomyelitis (EAE) model of MS. We found an acute blockage of CSF flow in the spinal cord of EAE mice, both from fluorescence and MRI analysis. A further investigation of the site revealed a potential blockage of CSF exit along the spinal nerves due to nerve edema and that decreased CSF flow is associated with meningeal T-cell invasion. In connection with these findings in the spinal cord, on-going efforts (Project IV) of this thesis focus on exploring vascular changes and the development of tissue hypoxia in the spinal cord of EAE by using multiple state of the art imaging methods.
Significance Our studies offer a novel perspective for the treatment of different inflammatory disorders of the CNS suggesting that targeting glymphatic function could counteract the effects of inflammation in the brain. We show that CSF influx and clearance are impaired in different models of neuroinflammation and importantly, that this may play a key role in the pathogenesis of meningitis and MS.

Kristina Munke

Time: Wednesday Feb 3rd, 14:00
Place:  Dora Jacobsohn, BMC D1513c (The half-time review will only be held via Zoom for the public, no audience is allowed)
Title: Mycobacterial regulation of the myeloid cell compartment – Role of the ESX-1 type VII secretion system
Main supervisor: William Agace
Co-supervisor:  Fredric Carlsson
Opponents: Fredrik Ivars och Marianne Jansson 
Zoom link:

Jana Rajova

Time: 2021-02-05, 09:00
Place:  D1513c Dora Jacobsohn, BMC, Sölvegatan 17, Lund. Please note that only supervisors and opponents may attend physically
Title: Development of spatial sequencing methods and applications in brain circuit repair in Parkinson's disease
Main supervisor: Assoc. Prof. Tomas Björklund, PhD, Lund University
Co-supervisor: Prof. Malin Parmar, PhD, Lund University, Malin Åkerblom, PhD, Lund University
Opponents: Shamit Soneji, PhD, Lund University, Asst. Prof. Nicholas Leigh, PhD, Lund University
Zoom link:; Meeting ID: 690 8023 6166


Recent advancements in molecular biology techniques enabled the development of spatial trascriptomics methods, aiming to analyze the transcriptomes of cells, while preserving the information about transcripts’ place of origin in the tissue.

Spatial Transcriptomics is a platform able to analyze transcriptome with 200 µm resolution. Here it is used to better understand dopaminergic transplants developed to relieve motor symptoms of Parkinson’s disease, and to study their effect on the host tissue. For this purpose, we have developed an improved bioinformatic pipeline. Besides reporting on gene expression in single tissue sections, it extends into analysis of broader gene expression patterns throughout many sections, removing confounding batch effects, otherwise obscuring biological differences. This enables identification of related tissue regions, morphological features and analysis of their unique transcriptional signatures; resulting in a better understanding of the whole tissue’s state and the differences among regions with unique transcriptional activity.

To showcase this, we compare data from several sections containing transplants from multiple sources of origin. Whereas without corrections, transplant region identification proves challenging, the correction algorithm uncovers a unique transplant signature throughout sections.

The second project aims to develop a technique for targeted sequencing of tissue sections with a single-cell resolution. This technique builds on surface-modified glass slides that preserve the captured transcriptome’s spatial information to 2 µm. The transcripts can be localized and identified by a padlock probe library, which through rolling circle amplification translates a single transcript into several thousand copies of a short DNA barcode-carrying molecule identifiable through in situ sequencing.

We present an approach though which, thousands of probes can be obtained for a fraction of the price of individual synthesis. 

Through a series of enzymatic reactions, a library of probes encased in a construct rendering it nearly infinitely amplifiable through PCR is transformed into pools of hundreds of ready-to-use probes. Each probe carries a barcode unique for its corresponding transcript.

Taken together, I here present proof-of-concept for a method, offering high resolution, flexibility, scalability, and cost-efficiency. The method has potential to extend current understanding of tissue states, where not only cells’ transcriptional activity, but also their spatial context present a crucial variable.

Kedir Hussen Hamza

Time: Tuesday Jan 26th, 14:00
Place:  Dora Jacobsohn, BMC D1513c.(The half-time review will only be held via Zoom for the public, no audience is allowed at the location, in order for the dissertation to be carried out according to FHM's guidelines.)
Title: Minor alterations in the intestinal microbiota composition upon Rotavirus infection does not affect susceptibility to DSS colitis
Main supervisor: Katharina Lahl
Co-supervisor:  William W Agace
Opponents: Jan Marsal and Mats Bemark
Zoom link:


Viral triggers at the intestinal mucosa can have multiple global effects on intestinal integrity, including relative protection from subsequent inflammatory bowel disease (IBD) induction in various models. Viruses can interfere with the intestinal immune system both directly and indirectly through commensal bacteria and hence cause-effect relationships are difficult to measure. Due to the complexity of putatively causative factors, our understanding of such virus-mediated protection is currently very limited. We here set out to better understand the impact that adult small intestinal rotavirus (RV) infection might have on commensal bacteria and in the severity of inflammatory bowel disease.

Using high-throughput sequencing of the V3-V4 region of the 16s rRNA gene, we probed whether rotavirus induces a global change in the gut microbiota composition. We further used an acute DSS colitis mice model to assess the impact of prior RV infection on the IBD disease severity. We observed no significant changes in the microbial diversity and richness of infected animals in the small or large intestine. Bray-Curtis dissimilarity index analysis of B-diversity did not reveal a significant difference upon RV infection. In addition, the differential abundance analysis of the microbiota between RV infected and control groups revealed no significant features in both the small intestine and large intestine niches.

Taken together, RV infection did not induce significant long-lasting microbiota community changes in the small or large intestine. We also found out that administration of live RV virus had no beneficial effect for the protection of DSS-induced colitis. Hence, RV infection does not generally impact on the intestinal homeostasis of adult mice and accordingly does not change the disease course of acute DSS colitis.

Elna Dickson

Time: Wednesday, February 17th 2021 at 13:00
Location: BMC I1345  (The halftime review will only be held via Zoom for the public, no audience is allowed at the location, in order for the dissertation to be carried out according to FHM's guidelines.)
Zoom link:
Title: Metabolic changes and the effect on disease progression in Huntington's disease
Main supervisor: Maria Björkqvist
Co-supervisor: Rana Soylu-Kucharz
Opponents: Malin Wennström and Margareta Nyman


Metabolic changes and the effect on disease progression in Huntington's disease


Huntington’s disease is a dominantly inherited neurodegenerative disease caused by CAG repeat expansion in the huntingtin gene. Mutant huntingtin is associated with widespread neuropathology and causes a combination of motor, cognitive, psychiatric, and metabolic symptoms. Clinical studies have shown that patients have a higher metabolism and late-stage weight loss despite adequate nutrition and intake of high fat- and caloric diets. In addition, higher BMI has been associated with a slower disease progression.


Huntingtin is expressed throughout the body and the mutation gives rise to both central and peripheral effects. The experimental mouse model R6/2 expresses exon 1 of mutant human huntingtin and develops similarly to patients an increased metabolism with pronounced weight loss. Through crossing with Ob/Ob mice, we have also generated a R6/2 Ob/Ob model which compared to R6/2 has a slower metabolism with weight gain. The models have been used to investigate two key points:
1) To determine how mutant huntingtin directly affects the peripheral tissue.
2) Utilizing viral vector systems to study the function of huntingtin in specific nerve cell pathways within the various structures in the brain that regulate our metabolism. 

Preliminary results

Overexpression of mutant huntingtin in hypothalamus of wild-type and R6/2 mice causes weight gain associated with increased food intake and significant changes in white adipose tissue. In R6/2 mice overexpressing mutant, the weight gain switches to weight loss during the corresponding end-stage of the disease. Orexin and oxytocin, hypothalamic hormones involved in regulation of weight- and appetite, and with suggested roles in browning of white adipose tissue, are significantly altered.
In addition to increased body weight and fat mass, the R6/2 Ob/Ob model displays functional differences in white adipose tissue compared to R6/2 mice, including lipolysis, insulin-stimulated glucose uptake and cell size distribution.
In Huntington’s disease, non-motor symptoms often precede motor symptoms by several decades. Understanding the central neurocircuits and their peripheral link to underlying metabolic alterations and other non-motor aspects may lead to new and more effective therapeutical interventions in the future.

Christian Westöö

Time: Thursday, February 11th 2021 15:00. Please note that only supervisors and opponents may attend physically
Location: Seminar Room, BMC C12, Lund
Zoom link will be announced
Title: The Role of Versican in Pulmonary Arterial Hypertension
Main supervisor: Docent Karin Tran-Lundmark, EMV and WCMM, Lund
Co-supervisors: Professor Anna Hultgårdh, Lund University, Dr Vinicio de Jesus Perez, Stanford, Assistant Professor Ljubica Perisic Matic, Karolinska Institutet
Opponents: Docent Anna-Karin Larsson Callerfelt, Lund University, Docent Anders Aspberg, Lund University


The Role of Versican in Pulmonary Arterial Hypertension

Pulmonary arterial hypertension (PAH) is a condition that leads to lethal right heart failure. Available treatments provide relief but are far from curative and the vascular remodeling in PAH has been difficult to decipher. Although central, the plexiform lesions are difficult to define, and there is no consensus regarding their potential hemodynamic impact. Versican is an extracellular matrix proteoglycan known to accumulate in systemic vascular disease, often colocalized with hyaluronan. We have previously shown that versican is abundant in PAH. However, its functional role warrants investigation.

Objective and Methods
Ongoing projects investigate the role of versican in PAH by in vitro studies and by use of in vivo models, with the hypothesis that versican accelerates disease progression. Another important focus for this thesis project has become to explore pulmonary vascular pathology, with special focus on plexiform lesions, by imaging paraffin-embedded tissue with synchrotron-based phase contrast micro-CT.

Preliminary Results

An article on how to 3D image pulmonary micro anatomy, where we described the vascular pathology of alveolar capillary dysplasia, was recently published.

The same synchrotron-based technique has also provided unique imaging of plexiform lesions in PAH, including proof of shunting between the pulmonary and the bronchial circulation within some lesions, making it possible to suggest a novel classification of plexiform lesions (currently under revision).
Preliminary results show that versican and hyaluronan partly colocalize in lesions of PAH. Inhibition of hyaluronan production decreased cell proliferation and versican production. A cleavage product of versican, previously shown to be biologically active, was found in the endothelium of PAH patients, but not in healthy controls.

Neither a global partial (two isoforms) nor an inducible complete knock-down of versican affected pulmonary hypertension in mice exposed to chronic hypoxia. However, recent data show that other models may be more suitable for studies of the role of versican in vivo.

The imaging technique and the novel classification of plexiform lesions have a potential to advance the PAH field significantly and will be used for the versican-focused projects. If the endothelial cleavage product of versican can be detected in blood, it may become a useful biomarker. 


Hani N. Alsafadi

Half-time review: Hani N. Alsafadi
Time: October 28th 2020 at 9AM
Place:  Dora Jakobsson BMC D15. Please note that only the committee members and opponents can attend physically. Welcome via Zoom link below.
Title: Context dependence of Hippo pathway in Idiopathic Pulmonary fibrosis
Main supervisor: Darcy E. Wagner, PhD
Co-supervisors: Matthias Magnusson, PhD – Lund UniversitySandra Linstedt, MD PhD – Region SkåneClaudio Cantù, PhD – Linköping University
Opponents: Johan Jakobsson, PhD, Filipe Pereira, PhD
Zoom link:


Idiopathic pulmonary fibrosis (IPF) is characterized by epithelial injury, deranged repair and excessive extracellular-matrix deposition. One largely unexplored pathway in IPF is the Hippo signaling which plays a central role in regulating organ size, cell proliferation and differentiation. The hippo pathway’s main function is inhibition of Yap/Taz through their phosphorylation. Several Hippo pathway components are decreased in IPF and Yap/Taz are active in proximal and distal IPF epithelia. We find active Yap/Taz in epithelial cells which express known phenotypic markers of proximal and distal lung epithelial progenitors and observed a dysregulation of genes downstream of Yap/Taz. Yap/Taz do not bind directly to DNA but to other transcription factors (TFs), indicating changes in transcriptional complexes in fibrotic epithelium.

Research question
The aim of this doctoral project is to identify pro-fibrotic YAP/TAZ transcriptional complexes in proximal and distal lung epithelia. First, primary cells from murine and human lung proximal and distal epithelia will be isolated. TFs interacting with Yap/Taz will be identified using cleavage under targets and release using nuclease (CUT&RUN) and pulldown mass spectrometry proteomics. Finally, the function of identified TFs will be validated in advanced 3D models.

Preliminary results
To isolate cells from mouse lung epithelia based on their anatomical location instead of surface markers, we developed a 3D printed device that allows for the simultaneous isolation of proximal and distal lung epithelial cells from an individual mouse. We validated the quality of isolated progenitor cells by their ability to differentiate in organoid formation assays and air-liquid-interface cultures. We have also successfully isolated human bronchial epithelial cells (HBECs; proximal epithelium) and human alveolar type II (hATII; distal epithelium) from healthy and diseased tissues. We have also validated the suitability of CUT&RUN to detect TF direct targets in mouse primary epithelial cells.

Finding the exact TFs activated during the fibrotic injury in epithelial cells will aid in finding effective druggable targets to treat pulmonary fibrosis as other homeostatic Yap/Taz activity could be needed for maintenance of regular biological functions such as healthy proliferation of cells.

Fatemeh Ahmadi

Half-time review: Fatemeh Ahmadi
Time: Wednesday November 4th, 14:00
Place:  Dora Jacobsohn (BMC D1513c)
Title: XCR1+ dendritic cells and IL-27 are required for intestinal Th1 homeostasis
Main supervisor: William W Agace
Co-supervisor: Katharina Lahl
Opponents: Vasileios Bekiaris and Bengt Johansson Lindbom
Zoom link:


The intestinal mucosa contains two major conventional dendritic cell (cDC)
subsets; cDC1 and cDC2, that play distinct non-redundant role in intestinal T cell homeostasis.
We have recently shown that CD11c-cre.IRF8fl/fl mice, that lack cDC1, are essential for
intestinal Th1 homeostasis and priming (1).

Research question
In the current study we wished to confirm that reduced intestinal Th1
numbers in CD11c-cre.IRF8fl/fl mice was due to a lack of cDC1, and assess the molecular
mechanisms driving intestinal Th1 homeostasis.

Method and preliminary results:
To determine whether intestinal Th1 responses are
dependent on cDC1 we generated XCR1-cre.Dtafl/fl and XCR1-cre.IRF8fl/fl mice, that
specifically and selectively lack cDC1. Similar to CD11c-cre.IRF8fl/fl mice, XCR1-cre.Dtafl/fl
and XCR1-cre.IRF8fl/fl showed reduced numbers of intestinal Th1 cells, demonstrating a key
role for cDC1 in intestinal Th1 homeostasis. We further show, using XCR1-cre.MHCIIfl/fl , Il-
12p35-/- and Il-27ra-/- mice that intestinal Th1 homeostasis requires MHCII expression by
cDC1, and is dependent on IL-27 but not IL-12 signaling. Further, using TCR transgenic
adoptive transfer models we identified a role for T cell intrinsic IL-27RA expression for Th1
differentiation in intestinal draining mesenteric lymph nodes. Finally, we show that the
intestinal Th1 compartment in mice establishes post weaning, with distinct kinetics to the
intestinal Th17 and FoxP3+ Treg compartment and is dependent on the microbiota and IL-27
signaling. Future experiments aim at determining whether cDC1 provide a key source of IL-27
for Th1 homeostasis, the turnover of intestinal Th1 cells in steady state and the impact of
inflammation on this turnover.

Intestinal Th1 cells are important for barrier protection and host defence, while
excessive accumulation of Th1 cells is thought to contribute to tissue inflammation.
Understanding the cellular and molecular mechanism driving intestinal Th1 development thus
important implications for human health.

1. Luda et al., IRF8 Transcription-Factor-Dependent Classical Dendritic Cells Are Essential for
Intestinal T Cell Homeostasis, 2016, Immunity 44, 860-874.

Caroline Haikal

Time: Monday August 31, 13:00
Place: I1345 (BMC)
Title: Peripheral alpha synuclein interactions
Main supervisor: Jia-Yi Li
Co-supervisor: Sara Linse
Opponents: Eva Ekblad and Maria Swanberg


Alpha-synuclein aggregation and accumulation is a central pathological feature of synucleinopathies, amongst which is Parkinson’s disease. Alpha-synuclein pathology is hypothesized to initiate in peripheral organs, primarily in the gastrointestinal tract and olfactory epithelium. We investigate the possible interactions of alpha synuclein with peripheral bacterial peptides and the potential role of peripheral alpha synuclein as a biomarker for disease.

We have performed kinetic experiments of alpha synuclein in the presence or absence of bacterial peptides. The resulting material has been added to cell culture and evaluated for its seeding potency. Mouse models of PD have been used to identify a potential new biomarker for the disease. Human intestinal tissues have been evaluated for the presence of alpha synuclein

Bacterial peptides accelerate alpha synuclein aggregation. The resulting alpha synuclein fibrils seed alpha synuclein in cell culture. The lingual papillae express alpha synuclein prior to motor symptom onset in mouse models of PD. Human intestinal alpha synuclein could be cleaved, limiting its identification with commercial antibodies.
Bacteria could trigger alpha synuclein aggregation in peripheral tissues. This has implications for the initiation of pathology. Establishing a relation between inflammation in the gastrointestinal tract and alpha-synuclein has implications for the initiation of disease. Identification of a novel biomarker can pave the way for preventative treatments.

Peng Huang

Time: 24th of August, Monday, starts 13:00
Place: Segerfalksalen (BMC A10)
Title: Glucose transporters: structure, function and putative targets in leukemia
Main supervisor: Karin Lindkvist
Co-supervisor: Pontus Gourdon
Opponents: Karin Stenkula and Jitka Petrlova


Glucose transporters are membrane proteins responsible for transporting glucose across the lipid bilayer in cells by facilitative diffusion. There are 14 mammalian glucose transporters (GLUT1-14), where GLUT1 is most ubiquitous while GLUT4 activity is insulin- stimulated and more cell- specific.
Acute myeloid leukemia (AML) is a group of hematological cancer with high heterogeneity. It was reported recently that enhanced glycolysis relates to decreased sensitivity for chemotherapy and poor prognosis in AML. Thus, targeting GLUT1 may represent a novel therapy in AML by sensitizing leukemic cells to chemotherapy.
GLUT4 is expressed in adipose tissue and translocates from intracellular compartments to the plasma membrane upon insulin stimulation, a process known as GLUT4 trafficking. Defects in this process are observed in insulin resistance and type II diabetic patients. ASPL, tether containing a UBX domain for GLUT4, sequesters GLUT4 intracellularly and releases it upon insulin stimulation.

Research questions/methods
We aim to study novel GLUT1 inhibitors (PGLs) and their effect and mechanism on glucose uptake from a structural aspects.
For GLUT4, we target to investigate its interaction with ASPL in vitro via biochemical and biophysical methods, and aiming to determine the complex structure by crystallography and/or cryo-EM. In the meantime, accurate GLUT4 subcellular localization and trafficking in human adipocytes have been studied applying immuno-gold labelling combined with TEM.

Preliminary results
(1) PGL13 and PGL14 show comparable inhibiting effects as CB and WZB 117 in giant vesicle assay.

(2) Prediction of binding positions of PGLs in GLUT1 and elucidation of binding mechanism by MD simulation and internal tryptophan fluorescence assay.

(3) High-quality ASPL protein and its C-terminal truncation have been produced.

(4) The interaction between GLUT4 and ASPL has been confirmed in vitro, and their binding domains have been determined and expressed recombinantly for crystallization and NMR.

(5) Human adipocytes ultrastructure has been captured by TEM, and localization of GLUT4 and ASPL in adipocytes have been verified.

PGLs, as a novel series of GLUT1 inhibitors, are promising drugs to develop further as a new treatment of AML.
Elucidating GLUT4 trafficking mechanism in adipocytes may be helpful to further understand insulin resistance and provide a new potential therapeutic targeting type II diabetes.

Sara Dahl

Time: Tuesday 16th of June, 10:00-12:
Place: BMC i1345 (full room)
Title: Cytotoxic and immunomodulatory properties of the antimicrobial peptide LL-37 in human cells
Main Supervisor: Bengt-Olof Nilsson
Co-supervisor: Daniel Svensson
Opponents: Jitka Petrlova and Anna-Karin Larsson Callerfelt


The human antimicrobial peptide LL-37 has important functions in innate immunity and inflammation. The peptide is toxic to different pathogens, and it works as an immune system modulator by e.g. recruiting immune cells and stimulate their production of inflammatory cytokines. However, high concentrations LL-37 is shown to display host cell cytotoxicity. The peptide can be internalized into host cells via endocytosis, but also by self-made pores in the cell membrane and therefore mediate cellular functions both by permeabilization and by receptor interactions. The aim of this thesis is to further evaluate the cytotoxic mechanisms and immune modulatory properties of LL-37 on human host cells. Experiments are performed in human cell lines and primary cells. Gene activity is assessed using real-time qPCR and protein measured using western blot or ELISA. Other methods include immunocytochemistry, colorimetric assays, fluorescence and confocal microscopy. Results show that treatment with LL-37 reduces cell viability and number in a concentration-dependent manner in human cells, and that this effect varies depending on cell type. We also show by measuring the influx/outflow of Ca2+ and lactase dehydrogenase, respectively, that LL-37 permeabilizes plasma membranes. In paper II we demonstrate that treatment with LL-37 induces release of nucleic acids and small proteins in LAD2 mast cells at concentrations of LL-37 where the cell viability remains unaffected. LL-37 internalization is confirmed in several host cells. More specifically, we show in paper I that blocking clathrin-mediated endocytosis in MG63 osteoblast-like cells reduces LL-37-uptake. However, the LL-37-induced cytotoxicity and permeability remains unaffected, indicating that LL- 37-evoked effects occur independently of LL-37-uptake via endocytosis. In paper III we show that LL-37 potentiates dsRNA-induced production of cytokines IL-6 and MCP-1 by up-regulation of TLR3 expression in human coronary artery smooth muscle cells. As a future project, the mechanism behind this finding will be investigated, studying the involvement of Ca2+ and the interactions between LL-37, double-stranded (ds) RNA and the TLR3 gene. Overall, gaining more knowledge in how LL-37 contributes to cytotoxicity and immune modulatory functions in human host cells is of great importance to better understand the role of LL-37 in inflammation and disease.

Nicholas Bèchet

Time:  Monday 15th of June, 14:00-16:00 (max 15 persons)
Place: BMC i1345
Title: CSF dynamics and drainage in mice, pigs and humans
Main Supervisor: Iben Lundgaard
Co-supervisor: Tomas Deierborg
Opponents: Malin Parmar & Niklas Marklund


Cerebrospinal fluid (CSF) is an ultrafiltrate of blood which circulates throughout the central nervous system (CNS) and the recent characterisation of the glymphatic system has fashioned new physiological roles for this fluid. The glymphatic system facilitates convective flow of CSF through the brain via aquaporin-4 water channels on astrocytic end feet. Glymphatic function predominates during sleep, specifically deep sleep, and has been shown to remove metabolites known to be toxic upon aggregation including lactate and amyloid-beta. Classically CSF exits the CNS and re-enters cardiovascular circulation through arachnoid granulations. This dogma has been accepted for 300 years, however, the dynamics of CSF, primarily its efflux, have begun to be questioned. Thus the aims of this PhD are to: 1)-contribute new knowledge to glymphatic physiology, 2)-develop novel techniques to study the glymphatic system, 3)-confirm the presence of the glymphatic system in higher mammals and 4)-readdress CSF efflux.

Aims have so far been addressed as follows:

1)-The glymphatic system is studied in animals through the injection of fluorescent tracers in the cisterna magna (CM). We found that glymphatic function fully develops in the cortex of mice after 2 weeks and that pericytes are necessary for its normal development. Apart from development we were also interested in uncovering means to modulate the glymphatic system and to this end we investigated how stimulation of cannabinoid-1 (CB-1) and cannabinoid-2 (CB-2) receptors might influence glymphatic based influx of CSF. A pilot study yielded promising results of increased influx via CB-1 signalling which could be a useful agent to enhance the clearance of toxic metabolites in neurodegeneration however further investigation is required.

2)- Glymphatic function is extrapolated by analysing the mean intensity of fluorescent tracer distribution in brain slices. We developed a new means to analyse glymphatic function in the whole brain by utilising optical clearing coupled to light-sheet microscopy. These methods allowed us to capture the entirety of the glymphatic system in the murine brain at 5 um slice steps and permitted 3D visualizations and several additional novel quantitative analyses. This is a useful tool for future analyses and studies.

3)- To understand the translational value of any potential future therapeutic manipulations of the glymphatic system it is imperative to validate its presence and physiology in higher mammals. We carried out glymphatic experiments in pigs through the injection of fluorescent tracer in the CM. These experiments confirm, using both light-sheet and confocal microscopy, that the glymphatic system persists in higher mammals and appears to be even more extensive than in rodents. This finding suggests that glymphatic clearance may be even more pivotal in higher mammals and may contribute more than anticipated to certain neuropathology.

4)- Considering that 500 mL of CSF is produced per day, and brain edema being a complication in stroke and traumatic brain injury, the efflux routes are important to study. Animal experiments point to the deep cervical lymph nodes as a primary detectable end path for CSF efflux. Herein we performed cisterna magna injection of silicon tracer in fresh-frozen human heads and show tracer exiting the skull across the cribriform plate and along spinal and cranial nerves. These exit routes may be targets for best reducing brain edema and enhancing metabolite efflux.

Fatima Daoud

Time: Tuesday 9th of June, 9:00 am (max 10 persons)
Place: BMC C12 seminar room
Title: Mechanosensitive transcription factors in smooth muscle and their role in vascular diseases
Main Supervisor: Sebastian Albinsson
Co-supervisors: Karl Swärd and Johan Holmberg
Opponents: Olof Gidlöf and Karin Tran Lundmark

Sibel Uzuncayir

Time: Thursday 26th of March, 13:00-15:00
Place: BMC I 1308
Title: Superantigen binding to human immune receptors
Main Supervisor: Karin Lindkvist
Co-supervisor: Eva Degermann   
Opponents: Pål Stenmark, Kajsa M.Paulsson 


Background: Superantigens are toxins that are known to lead to food poisoning and toxic shock syndrome in humans. The conventional molecular mechanism is that they cross link MHC II and the αβ T cell receptor outside the antigen binding region. This causes a massive T cell activation, cytokine production and immune response.

However, other receptors have been identified for superantigen binding. It was reported that the superantigen SEA is able to bind to γδ T cell receptor and the human cytokine receptor gp130. The binding details and the three-dimensional structure are the focal point of my project. We also want to investigate the biological function of the interaction. 

Method: To resolve the structural details of the supernatigen-gp130 complex, the proteins were recombinantly expressed and purified. Mass spectrometry cross-linking (MS-XL) analysis was performed to identify crucial residues for the complex formation and the binding was investigated by applying surface plasmon resonance (SPR). Nevertheless, our main aim is the three-dimensional structure of the complex via X-ray crystallography.

Preliminary results: The proteins gp130, γδ T cell receptor and the superantigen have been produced. The SPR-results show that the superantigen binding is specific to human gp130, as we cannot detect binding to the mouse and rat variant of gp130. The affinity of the complex is approximately 0.6 μM. The superantigen uses another binding site than the well-known gp130 activator, human leukaemia inhibitory factor (LIF), as LIF and the superantigen do not compete for binding to gp130. The preliminary MS-XL results show that the superantigen binds to domain 2 of the human cytokine receptor, while LIF binds in between domain 2 and 3. Based on these results a computational model of the complex of superantigen and gp130 will be generated. Furthermore, crystallization experiments were initiated.

Significance: Gp130 is expressed all over the human body and involved in the regulation of immune response, hematopoiesis, pain control, bone metabolism and survival of motor and sensory neurons. The γδ T cell is the smaller subset of T cells in human, but the amount becomes upregulated upon bacterial infection. The γδ T cell receptor is involved in initiation and propagation of immune response. The binding of superantigens and alteration of the regular signal pathways of these immune receptors might have a large impact in humans.

Oskar Rosmark

Time:  Wednesday, February 12th at 10.00
Place: C12 seminar room (C1241a)
Title: Proteomic exploration of alveolar remodeling with cell culture in decellularized lung matrices
Main Supervisor: Gunilla Westergren-Thorsson, Anna–Karin Larsson Callerfelt, Oskar Hallgren and Leif Eriksson
Opponent Karin Tran Lundmark and Patrik Önnerfjord


Chronic lung diseases such as chronic obstructive lung disease (COPD) and idiopathic lung fibrosis (IPF) involve remodeling of the lung parenchyma, with loss of alveolar tissue and emphysema in the former case, and fibrotic scarring in the latter. The mechanisms governing physiological and pathological extracellular matrix (ECM) turnover in the lung is poorly understood, with incomplete knowledge regarding the role and importance of specific cell types.

We hypothesize that pathological remodelling in chronic lung disease are driven by a disrupted reciprocal communication between cells and surrounding ECM. We aim to establish new methodology for studies of cell-ECM interactions and explore ECM turnover by mesenchymal and epithelial cells in lung parenchyma.

We have established a method to produce acellular slices of lung parenchyma from patient derived lung tissue. These 350 µm thick lung slices have a preserved 3-dimensonal architecture to which repopulating cells interact with. Applying stable isotope labelling with amino acids enable monitoring of ECM turnover with mass spectrometry as labeled newly synthesized matrix proteins can be distinguished from pre-existing proteins in the decellularized tissue.

Our initial study evaluating the methodology with culture in decellularized lung slices demonstrate the importance and regulatory effect of a pre-existing matrix. ECM production by primary human fibroblasts is both quantitatively and qualitatively altered by culture in decellularized lung ECM compared to traditional monolayer culture on plastic surfaces. Culture in lung ECM gave a prominent increase in the accumulation of decorin, biglycan and lumican. These three proteoglycans are expected to play a role in the remodeling of lung ECM, e.g. by participating in assembly and organization of collagen fibers. We also demonstrate an instructive property of lung ECM as repopulating fibroblasts cultured in ECM from healthy donors and IPF-patients synthesized proteins resembling the composition of the surrounding ECM.

Our methodology is readily applicable to other experimental systems utilizing decellularized biological scaffolds and could prove a valuable tool for studies of tissue remodeling. Better understanding of lung remodeling may reveal new avenues for disease modifying treatment for chronic lung disease.

Nadja Gustavsson

Time: Monday 20/01/20 at 15:15
Place: BMC I1309, Lund
Title: Amyloid protein aggregation related to mixed Alzheimer’s and Parkinson’s diseases. Amyloid-β or α-synuclein: who’s first to blame?
Supervisor: Assistant Professor Oxana Klementieva
Opponents: Daniella Ottosson, Ph.D, Andreas Heuer, PhD


Alexandra Aidoukovitch - Production and function of the antimicrobial peptide LL-37 in human saliva

Time: Tuesday, 17th December at 13:15
Place: BMC I:1345
Supervisor: Professor Bengt-Olof Nilsson
Opponents: Dr. Cecilia Andersson, Department of Experimental Medical Science, Lund University; Docent Helena Fransson, Faculty of Odontology, Malmö University. 


The human antimicrobial peptide LL-37 is involved in the first line of defense against microorganism. It possesses immunomodulatory properties in addition to its antibacterial, antiviral, and antifungal effects. The peptide is of great interest for etiology of oral diseases because of its bactericidal effects against both gram-positive and gram-negative bacteria. Dental caries, also referred to as tooth decay, is the most prevalent oral disease. It is a multifactorial disease, where both the composition and quantity of saliva are important parameters for assessment of caries-risk. In this doctoral thesis, the overall objective is to enhance knowledge about production and functional properties of LL-37 and its pro-form hCAP18 in human saliva.  As working material, mainly isolated saliva from the major salivary ducts, whole saliva, glandular tissues and salivary cells are studied. Several analysing methods are used to quantify and visualize protein levels and distribution of LL-37 in human saliva, oral cells and tissues. The results demonstrate that all three major salivary glands contribute to salivary hCAP18/LL-37 content and that salivary hCAP18/LL-37 originates from intravascular neutrophils. Furthermore, the data propose that desquamated epithelial cells harbour hCAP18/LL-37, implying that these cells might play a prominent role in innate immunity. In future perspectives, we will investigate if epithelial cells of saliva can express and produce LL-37 as well as their role in the defense against pathogens. From a more clinical point of view, we plan to examine hCAP18/LL-37 contents in different fractions of saliva to assess clinical pathophysiological correlations between hCAP18/LL-37 levels and dental caries incidence. The highly potent LL-37 peptide mediates various mechanisms of actions and is of growing interest as a potential endogenous treatment target. Thus, elucidating the effects of salivary LL-37 in relation to oral pathology is of importance to build a foundation for the future development of novel therapeutic and diagnostic strategies. 

Konjit Getachew - Optimal neonatal humoral responses to Rotavirus require both cDC1 DCs and T cells

Time: December 5th at 10:00am
Place: BMC, I1345
Supervisors: Katharina Lahl and William Winston Agace
Oponents: Joan Yuan and Marcus Svensson Frej

Rotavirus is an intestinal pathogen that primarily affects infants and young children. Available vaccines show variable efficacy. Dendritic cells (DCs) are crucial for the initiation of immune responses and therefore important targets for vaccines. The two major DC subsets, called cDC1 and cDC2, differ in their capacity of inducing specific adaptive immunity in adults, but their distribution and potentially differential roles in neonates are largely unknown. After confirming that steady state neonates indeed harbored considerable numbers of both cDC1 and cDC2 DCs in the intestines, we set out to address whether specific DC subsets had the capacity to induce humoral responses towards neonatal rotavirus infection. As in adult mice, rotavirus induced a massive T cell-dependent but DC subset-independent accumulation of total B cells in gut-associated lymphoid tissues. cDC1-deficient mice however lacked the substantial plasmablast induction observed in response to rotavirus infection in suckling wildtype mice. In contrast to a specific requirement for IgA induction in response to rotavirus infection in adult mice, cDC1 were generally required for the plasmablast accumulation with no preferential bias towards IgA in neonates, suggesting that mechanisms of DC-induced B cell induction and isotype switching may differ in the developing versus the adult immune system.

Samuel Cerps - Altered viral resistance and tolerance as pathogenic mechanisms of allergic airway inflammation

Time: November 26rd 2019 kl 15:00
Place: BMC i1309
Supervisors: Lena Uller, Hamid Akbarshahi, Cecilia Andersson, Leif Bjermer, Anna-Karin Larsson Callerfelt, Cecilia Ahlström-Emanuelsson.
Opponents: Arne Egesten and Anja Meissner

Asthma is chronic inflammatory airway disease characterized by reversible expiratory airflow limitation. There is a large subgroup of asthmatics with a higher frequency of episodes of severe worsening of the disease (exacerbations) that lack efficient treatment options. Up to 80 percent of all exacerbations are triggered by Rhinoviruses that cause the common cold. Although the mechanisms of exacerbation are not fully understood, deficient production of interferons is a favored explanatory factor, suggesting a defect in pathogen resistance. Additionally, there is an exaggerated injurious immune response towards pathogens, suggesting involvement of a dysfunctional tolerance mechanism as a factor of developing exacerbations.

Aim and Methods
This PhD project aim to study how defects in both pathogenic resistance and tolerance contribute to allergic airway inflammation and exacerbations of chronic inflammatory lung diseases using translational in vitro and in vivo research strategies. Briefly, we culture primary bronchial epithelial cells from healthy individuals and patients with different asthma severity which are included for the mechanistic studies. Furthermore, experimental animal models of asthma and asthma exacerbations are also included.

In a house dust mite (HDM) mouse model of rhinovirus-like -induced asthma exacerbation, we have demonstrated that absence of IFN-β augments markers of pathogenic necroptotic cell death at exacerbation. We also demonstrate that the type-2 upstream cytokine TSLP may have a role in neutrophilic inflammation developing early at rhinovirus induced asthma exacerbation. Our in vitro data propose that HDM challenges and HDM atopy might reduce the ability of bronchial epithelial cells to produce cytokines involved in anti-bacterial defence possibly leading to severe exacerbations.

Aberrant cell death pathways due to defects in anti-viral response could be one potential mechanism linking a defective pathogenic resistance to a dysfunctional tolerance mechanism and thus be target for molecular intervention.

Publish papers:
Cerps, S., Menzel, M., Mahmutovic Persson, I., Bjermer, L., Akbarshahi, H., & Uller, L. Interferon-β deficiency at asthma exacerbation promotes MLKL mediated necroptosis. Scientific Report 2018
Mahmutovic Persson, I., Menzel, M., Ramu, S., Cerps, S., Akbarshahi, H., Uller, L., Il-1β mediates lung neutrophilia and Il-33 expression in a mouse model of viral-induced asthma exacerbation. Respiratory research, 2018

Premkumar Siddhuraj -  Mapping / Decoding of spatial immune cell patterns and single cells phenotypes in human lungs 

Time : Tuesday, November 5th at 10:00
Place: BMC, I1345.
Supervisors: Prof. Jonas Erjefält,  Prof. Leif Bjermer .
Opponents:  Lec. Elllen Tufvesson , Prof. Eva Ekblad.


Airway inflammatory diseases are one the leading cause of mortality rates globally, they follow as; Chronic obstructive pulmonary disease (the third leading cause of death worldwide), asthma (affects more 300 million people) and fibrotic lung diseases (13 to 20 out of every 100,000 people). Despite recent advancements, the immune cell phenotypes and their infiltration pattern in diseased lung microenvironments are poorly known. 

Methodology & Results:

We have developed state of the art- High-throughput Histomic Single-Cell Profiling method.

As our primary focus was mast cells, we have applied our methodology to phenotype tissue mast cells in lung sample from patients (COPD & lung fibrotic diseases), human lung tissue ex-vivo studies and humanized (NSG-SGM3) mouse model. Our result debunks the classical mast cell phenotypes (MCT& MCTC) by uncovering a non-clustered and microenvironmentally-dictated protease plasticity and reversed patterns of protease mRNA and protein expression. 

The next project involves the holistic mapping of human innate and adaptive immune cell response in the humanized mouse model. Our results render novel insights of human immune cell infiltration pattern in mouse lung and their striking similarities with human lung pathology of COPD patients.

Our third project deals with human basophil phenotypes in peripheral blood and human lung tissue sections.  Our results suggest that human basophils displayed marked heterogeneity based on their granule content and questions the existing pan markers to explore lung tissue basophils.


Our goal is to able to grasp the true dynamic range of protein and mRNA expression at single-cell resolution and perform a comprehensive mapping of immune cell infiltration pattern in diseased lungs. 

Måns Kadefors - Characterization of mesenchymal stromal cell sub-populations in lung tissue

Time: 9.00 12th June
Place: C12 seminar room
Supervisors: Gunilla Westergren-Thorsson, Sara Rolandsson-Enes and Stefan Scheding
Opponents: Paul Bourgine and Niels-Bjarne Woods

Mesenchymal stromal cells (MSCs) are promising candidates for cell-based therapies in different diseases, and its hypothesized that lung-derived MSCs could be particularly suitable to target lung diseases. However, the identity and role of native MSCs in the lung is not fully understood, leaving a lot of questions regarding the basic biology of MSCs to be answered before we can harness their potential therapeutic abilities. We have previously described a tissue-resident MSC in biopsies from lung transplanted patients based on CD90 and CD105 expression. The overall hypothesis of the project is that MSC together with other stromal cells such as fibroblasts, constitute a heterogeneous pool of cells in the lung with functionally different sub-population. By semi-quantitative mass spectrometry analysis of cell proteome, we have been able to identify potential cell surface markers for lung fibroblasts, with differential expression between MSCs and fibroblasts. In addition, prospective sub-populations of MSC could be identified based on expression of these and other cell surface marker from the mass spectrometry data. Isolation of more homogeneous MSC populations can enable the recognition of their identity and function in normal and disease lung and further allow us to identify sub-populations with specific therapeutic attributes.

Julia Nilsson - Characterization of the spontaneous and mixed type 1/type 2 inflammatory syndrome and its subsequent fibrosis development in the NIF mouse. 

Time: Tuesday, May 28th 2019, 9:00
Place: BMC I:1345
Supervisor: Dan Holmberg
Co-supervisors: Madeleine Durbeej-Hjalt and Anja Schmidt-Christensen
Opponents: Fredric Carlsson and Lena Uller

Fibrosis is the result of excessive accumulation of extra cellular matrix proteins during wound healing, which can have detrimental effects to the affected tissue and can lead to organ failure. Chronic liver inflammation independent of etiology can lead to liver fibrosis and eventually cirrhosis. These pathological processes include infections, trauma and non-alcoholic steatohepatitis (NASH), the latter estimated to be the most common liver disease in industrialized countries. Though induced animal models have been instrumental in identifying several key cells, mediators, and processes that are likely to be involved in human liver fibrosis, there are still no efficient anti-fibrotic treatments available to date. A major limitation in the attempts to understand the underlying mechanisms and to establish efficient anti-fibrotic treatment protocols has been the restricted set of suitable animal models, where one obstacle has been the difficulty in reproducing the process of persistent inflammation leading to the tissue remodeling and fibrosis that is commonly observed in human fibrotic disorders.

Aim and method
To characterize the development and progression of the spontaneous inflammation and subsequent fibrosis of the NIF mouse, and to use this model to study and elucidate the possible mechanisms leading to the development of fibrosis.

In the liver, the NIF mouse displays inflammation and fibrosis particularly evident around portal tracts and central veins and shows characteristic type 2 inflammation where the extensive cellular infiltration consists mainly of granulocytes, particularly eosinophils and neutrophils, and the levels of IL-4, IL-5 and IL-13 are significantly elevated. This inflammatory syndrome is mediated by a transgenic population of natural killer T cells (NKT), and through upregulation of TGF-β, due to the combined production of high levels of Th2 cytokines and pro-inflammatory factors, by the transgenic NKT cells, the hepatic stellate cells are activated, leading to the development of severe fibrosis.

The liver is one of the organs where fibrosis constitutes a serious clinical problem with a major unmet therapeutic need. In this context the NIF mouse offers a unique tool for gaining further insight into the underlying mechanisms of fibrosis development in order to identify potential drug therapy targets.

Published papers:
Fransén-Pettersson N, Deronic A, Nilsson J, Hannibal TD, Hansen L, Schmidt-Christensen A, Ivars F and Holmberg D. The Immunomodulatory quinolone-3-carboxamide paquinimod reverses established fibrosis in a novel mouse model for liver fibrosis. PLoS One. 2018; 13(9): e0203228.
Fransén-Pettersson N, Duarte N, Nilsson J, Lundholm M, Mayans S, Larefalk Å, Hannibal TD, Hansen L, Schmidt-Christensen A, Ivars F, Cardell S, Palmqvist R, Rozell B and Holmberg D. A New Mouse Model That Spontaneously Develops Chronic Liver Inflammation and Fibrosis. PLoS One. 2016; 11(7): e0159850.

Submitted manuscripts:
Nilsson J, Hörnberg M, Schmidt-Christensen A, Carlus M, Mayans S and Holmberg D.
NKT cells drive both NLRP3 inflammasome-mediated inflammation and fibrosis in the NIF mouse model for liver fibrosis.
Journal of Hepatology

Nilsson J, Fardoos R, Hansen L, Lövkvist H, Pietras K, Holmberg D and Schmidt-Christensen A.
Recruited fibroblasts reconstitute the Peri-islet membrane: A longitudinal imaging study of human islet grafting and revascularization.

Sangeetha Ramu - New aspects of allergic mechanism and innate immunity in asthma
Time: Monday, 3rd June at 10:15 am
Place: BMC C12 seminar room (C1241a)
Supervisor: Lena Uller 
Co-supervisors: Leif Bjermer, Hamid Akbarshahi, Cecilia Andersson
Opponents: professor Jonas Erjefält, associate professor Anna-Karin Larsson Callerfelt,

Allergy and respiratory viral infections have been recognized as two major important risk factors for asthma exacerbations. Asthma exacerbations are characterised by inflammation and reduced lung function. Rhinovirus (RV) infection is a main trigger of asthma exacerbations. Recent studies showed that virus and allergens may have a synergistic effect and increase the risk for acute asthma exacerbations.

Aims and method
The aim of this thesis work is to investigate the innate immune response of airway epithelial and smooth muscle cells to common allergens, RV-infections and combination of both. We employed in vitro cultures of cell lines or primary human bronchial epithelial cells (BECs) and bronchial smooth muscle cell (BSMCs) from healthy and asthmatic patients to study alarmin and cytokine release as well as the regulatory molecular mechanism involved.

Our results demonstrated that, BECs release ATP and the pro-inflammatory cytokine IL-8, in response to stimulation with four different allergens; house dust mite (HDM), A. alternata, B. pendula and A. vulagris. Only HDM induced uric acid release in BECs as well as in our HDM-induced mouse model of allergic airway inflammation. Using specific inhibitors, we found that these responses were mainly dependent on serine proteases. We further stimulated BECs with the mast cell proteases tryptase and chymase and the results showed that these proteases induced ATP, IL-8 and IL-6 release and reduced viral-induced IFN-beta response. Reduced anti-viral response was associated with decreased pattern recognition receptors expression in BECs. Further we confirmed that mast cell proteases can damage the epithelial integrity by reducing the tight junctional proteins expression. Finally, we have investigated RV-induced IL-33 expression and regulating mechanisms from healthy and asthmatics BSMCs. Our results suggest that RV-induced IL-33 expression was higher in non-severe asthmatics compared to healthy and severe asthmatics. This response was mainly regulated through TLR-3 and activation of downstream signalling pathway TAK1 in BSMCs.

In conclusion, our studies so far have shown that RV-infection and allergen proteases play a major role in producing alarmins and cytokines which is relevant to asthma exacerbations in both BECs and BSMCs.

Franziska Kopietz - AMP-activated protein kinase (AMPK) in adipose tissue

Time: Wednesday, 3rd of April at 10:00
Place: BMC C11 seminarroom (C1141a)
Supervisor: Olga Göransson
Co-supervisors: Eva Degerman
Opponents: Ulrika Krus and Fredrik Leeb-Lundberg


The inability of subcutaneous adipose tissue to adequately store lipids is a strong predictor for the development of insulin resistance and type 2 diabetes (T2D). Insulin is known to play an important role for lipid storage, however, the exact mechanism underlying for example its positive effect on fatty acid (FA) synthesis, so far remains unclear. Previous studies suggest that some effects of insulin on lipid storage are mediated by AMPK, involving its phosphorylation at S485 and subsequent inactivation. Additionally, AMPK activation is considered a useful strategy for the treatment of T2D. In contrast to liver and muscle tissue, the effects of AMPK activation on adipocyte metabolism are less well characterized.

Aims and methods
One aim of this study is to characterize the insulin-induced inhibition of AMPK and reveal its underlying mechanisms, with the ultimate goal to determine how insulin stimulates FA synthesis. For this purpose, primary adipocytes, including cells overexpressing AMPK S485 mutant versions, are treated with insulin. AMPK activity is monitored by in vitro kinase assay and western blotting. Secondly, we are investigating the effect of the novel AMPK activators A-769662 and 991 on adipocyte metabolism. Primary rodent and human adipocytes are treated with the different activators and lipolysis as well as glucose uptake are measured. Furthermore, upstream signaling pathways are monitored by western blotting.

Preliminary results
The results so far indicate that S485 phosphorylation is not a critical requirement for insulin-induced AMPK inhibition and subsequent induction of FA synthesis. Furthermore, we showed in an already published study that AMPK activation by the novel activators has no antilipolytic effect in primary human adipocytes, in contrast to the previously used and less specific activator AICAR. A current investigation on glucose uptake has generated a large amount of preliminary results, which suggest differential effects of the two novel activators on this metabolic pathway.

With this research, we will increase our basic understanding on how insulin can promote lipid storage. Furthermore, it will contribute to a better understanding of the effects of AMPK activation specifically in adipose tissue.


Martina De Santis - Development of a hybrid alginate-ECM hydrogel as a potential bioink for 3D bioprinting of lung tissue

Time: Friday, December 14th at 10:15
Place: Dora-Salen, D15, BMC
Supervisor: Darcy Wagner
Co-supervisors: Gunilla Westergren-Thorsson, Sandra Lindstedt
Opponents: Lena Uller, Lund University and Chelsea Magin, University of Colorado Denver 

AbstractLung transplantation is the only option for end-stage lung disease, but tissue shortage remains problematic. Generating lung tissue ex vivo using tissue engineering approaches could help overcome organ shortages, but scaffold materials and manufacturing approaches to generate lung tissue remain elusive. Recent advances in 3D printing permit the generation of complex shapes, but potential bioinks remain unknown and will need to be tailored for each tissue or organ. We hypothesized that a hybrid pre-hydrogel solution generated by combining the engineering reproducibility of a synthetic material, alginate, with a biologic material, lung derived extracellular matrix (ECM), could be a suitable bioink for 3D bioprinting lung tissue. We successfully generated hybrid hydrogels from alginate and decellularised mouse and human lung ECM. Oscillatory rheometry measurements indicate the shear thinning properties of the hybrid bioink and a higher mechanical stability of the hybrid hydrogels compared to alginate hydrogels. Hybrid bioinks also prevented noticeable cell sedimentation over 1-hour time points. Lung epithelial cell lines (MLE12 and A549) and an endothelial cell line (b-End3) were distributed homogenously within the hydrogels. Cells remained viable for up to 7 days, with increased proliferation (30%) in hybrid hydrogels as compare to alginate alone. Chick chorioallantoic membrane (CAM) assays indicate that the hybrid hydrogels induce angiogenesis, a beneficial property for long term graft survival. The hybrid hydrogel is thus a promising bioink for 3D bioprinting pulmonary tissue.

Laura Andreoli - Striatal pathways in dystonia and dyskinesia

Time: 20th of December, from 10:00 to 12:00,
Place: room I1345, BMC
Supervisor: Angela Cenci Nilsson (Basal Ganglia Pathophysiology)
Reviewers: Daniella Ottosson and Tomas Björklund

Background: Our well-coordinated movements depend on the functional interaction between two neural pathways within the basal ganglia. These pathways originate from striatal neurons that express different types of dopamine receptors. Specifically, neurons giving rise to the so-called direct pathway express the stimulatory D1 receptor (D1R) whereas neurons forming the indirect pathway express the inhibitory D2 receptor (D2R). In Parkinson’s disease, a severe dopamine depletion causes insufficient stimulation of both D1R and D2R, disrupting the physiological interplay between direct and indirect pathway. Further imbalances in pathway activation are caused by L-DOPA, a dopamine precursor that provides the main treatment for PD. While L-DOPA is initially effective in improving parkinsonian motor symptoms, it induces different types of abnormal involuntary movements (termed, L-DOPA-induced dyskinesia, LID) within a few years of treatment.

Aim: This thesis work aims at dissecting the contribution of specific basal ganglia pathways and dopamine receptors to different types of abnormal involuntary movements that complicate the dopaminergic treatment of PD.

Methods: Studies are performed in transgenic mice expressing fluorescent reporter proteins, Cre recombinase, and/or dopamine receptor genes flanked by LoxP sites (“floxed”). Mice are rendered parkinsonian by dopamine-depleting lesions, and Cre/LoxP recombination technologies, combined with pharmacological tools, are used to selectively alter the activity of different striatal pathways and dopamine receptors while studying the animals’ behavior. Moreover, we are using a virally mediated Cre/loxP system to selectively knockout the D2R in indirect pathway striatal neurons.

Results: The results so far obtained demonstrate that (ii) both parkinsonian and dyskinetic behaviors are bidirectionally modulated by the two striatal output pathways; (ii) chemogenetic activation of direct pathway neurons can induce a dyskinesia similar to LID only if it mimics the signaling events associated with D1R stimulation; (iii) it is possible to discriminate between fast (‘hyperkinetic’) and slow (‘dystonic’) components of LID in the mouse using separate rating scales; (iv) treatments that inhibit indirect pathway striatal neurons enhance only the dystonic components of LID. 

Conclusions:  The present results shed new light on the role of striatal pathways and dopamine receptors in generating different types of movement disorders in PD, paving the way for the development of precise therapeutic interventions.

Matilde Forni - Deep brain stimulation in the periaqueductal gray reduces pain perception in acute pain and hyperalgesia in awake freely moving animals

Time: Wednesday, December 12th at 10:00
Place: Room E24 at Medicon Village House 404
Supervisor: Prof Jens Schouenborg
Opponents: My Andersson and Fredrik Bengtsson


To develop effective treatments for long lasting pain it is fundamental to understand how the perception of pain is modulated by endogenous analgesic centers in the awake individual. Unfortunately, very little is known about these aspects as most studies have been based on the assessment of motor responses rather than on pain perception. To address this issue, we made use of a recently developed animal model in which the nociceptive input to primary somatosensory (S1) cortex, an area related to perception of pain magnitude, is monitored with implanted electrodes developed in our laboratory (Ljungquist et al. 2016). To clarify how nociceptive input to S1 cortex is modulated during analgesia, we implanted a novel ultra-flexible microelectrode cluster for Deep Brain Stimulation (DBS) in the periaqueductal grey substance (PAG) in same animals. It is known that electrical stimulation of PAG can inhibit motor responses elicited by nociceptive stimuli, but the effect on pain perception is poorly understood. Moreover, due to the complexity of the area, it remains extremely complicated, to find “pure” analgesic areas and to not trigger other undesired behaviors. By selecting subsets of microelectrodes from the cluster we found that it is indeed possible to induce exclusively analgesic effects. Moreover, the PAG-DBS induced a reduction in both nociceptive input to the S1 cortex and withdrawal reflexes elicited by nociceptive stimuli during both acute pain and hyperalgesia; a possible dissociation between the withdrawal reflexes and the cortical potentials was found during DBS-induced mild analgesic effects, but further analyses have to be performed to clarify in which particular conditions this might occur. The parallel monitor of the rats EcoG showed that the PAG-DBS does not cause any sedative or arousal state. Further studies investigating changes of nociceptive-related signals in other brain areas involved in pain processing will be essential to clarify the function of PAG in the pain system and whether implantation of microelectrodes for DBS in PAG can be used to treat chronic pain.

Joy Nakawesi - Batf3-dependent dendritic cells facilitate IgA induction towards rotavirus in a CD4+T cell- and TGFb-dependent manner

Time: Wednesday, November 21st at 14:00
Place: Dora Jacobsohn BMCD15
Supervisor: Katharina Lahl
Opponent: Bengt Johansson Lindbom and Dirk Baumjohann


Rotavirus (RV) is one of the leading causes of life-threatening diarrheal diseases among young children. Based on correlative studies, RV-specific intestinal IgA is one of the principal effectors for long-term immunity. Despite its prominent role in the anti-RV response, very little is known about the mechanisms leading to IgA induction towards viruses at the intestinal site. Intestinal classical Dendritic Cells (cDCs) were shown to facilitate both T cell-dependent and -independent secretory IgA. However, whether cDCs can provoke intestinal anti-RV antibody responses during RV infection is unclear.

 Here, we show that Batf3-dependent cDC1 DCs, but not cDC2 DCs, are critical for the optimal induction of RV-specific IgA responses in the mesenteric lymph nodes (mLNs). Batf3-deficient mice shed RV longer than littermate controls. This correlated with fewer RV-specific CD8+ T cells and a lower fecal RV-specific IgA titer. We used GFP-labelled rotavirus-like particles (VLP2/6) to identify RV-specific B cells in infected mice on a single cell level. Compared to littermate controls, Batf3-deficient mice had significantly fewer RV-specific IgA+ B cells in mLNs while the total B cell numbers were not affected. The bulk of the RV-specific antibody response was T cell dependent. Sensing of type I interferon on DCs played a redundant role, as mice lacking the type I interferon receptor on all DCs generated comparable IgA responses to their littermate controls. Class switching to IgA partly depended on the αvβ8 TGFβ-activating integrin expression on cDC1 DCs, suggesting a role for TGFβ.

Together, our results show an essential role for cDC1 DCs in the generation of the RV-specific IgA response. Given that cDC2 DCs are crucial in driving IgA during steady-state but seemingly do not contribute to RV specific IgA responses, we propose that the capacity of DC subsets to induce IgA at the intestinal wall reflects the nature of the stimulating trigger as opposed to an intrinsic capability of a particular DC subset.

Shelby Shrigley - From Cell Reprogramming to Personalised Medicine

Time: Tuesday 16th October at 10:00
Place: A11 conference room
Supervisor: Malin Parmar
Co-supervisors: Cecilia Lundberg
Opponents: Maria Swanberg & Yuriy Pomeshchik


Parkinson’s disease (PD) affects approximately 6 million people worldwide and is characterised by the progressive loss of dopaminergic (DA) cells in the substantia nigra and accumulation of pathological a-synuclein. This leads to motor impairments including bradykinesia, rigidity, resting tremor and postural instability. Cell replacement therapy aims to replace the midbrain DA neurons which have been lost in the disease with the aim to restore normal motor function.

Research Method

In 2006, the stem cell field was revolutionised by the discovery of cellular reprogramming. This allows somatic cells to be reprogrammed either into induced pluripotent stem cell (iPSCs) or directly into induced neurons (iNs) by forced expression of specific factors. This creates the possibility to use patient-specific cells or cells from matched donors which could improve engraftment and reduce the risk of immune rejection. The first goal of my thesis was to develop a protocol to reprogram adult human fibroblasts into functional neurons. Following this, we also explored the possibility to reprogram these cells specifically towards a DA subtype. Our next step will to be to assess if reprogrammed DA neurons can survive intracerebral transplantation and function on par with stem cell derived and fetal DA neurons. Finally, we will also investigate if patient specific cells display any pathological features which may reduce their therapeutic potential.

The aim of my thesis is to evaluate if human reprogrammed neurons could be a suitable alternative for cell therapy for PD. The results will help to pave the way for future research assessing their potential for brain repair and disease modelling.

Marcella Birtele - Functional analysis of neurons for cell replacement therapies in Parkinson´s Disease

Time: Friday, August 24th, at 13:00
Place: A11 conference room

Title: Functional analysis of neurons for cell replacement therapies in Parkinson´s Disease
Supervisor: Malin Parmar
Co-supervisors: Johan Jakobsson and Daniella Rylander Ottosson
Opponents: My Andersson and Henrik Ahlenius


Parkinson’s Disease (PD) is the second most common neurodegenerative disorder after Alzheimer, affecting from 0.5 to 1% of the population in the range of 65-69 years of age and between 1 to 3% of the population over 80 years of age (Elbaz et al., 2016).

At the cellular and molecular level, the principal hallmark of the pathology is represented by an accumulation of the alpha synuclein protein in form of Lewy Body (LB) aggregates. Among other locations, LBs are found in the Substantia Nigra pars compacta (SNpc) and they are believed to induce the death of a specific subset of cells, the dopaminergic neurons (DA) (Spillantini et al., 1997). 

Research method:
A possible approach to restore the function of the dopaminergic neurons is represented by cell replacement therapy.

Recently, the development of new protocols for the generation of dopaminergic cells from pluripotent stem cells (PSC) (Kriks et al., 2011, Kirkeby et al., 2012, Doi et al., 2014, Nolbrant et al.2017), has opened the possibility to use these cells in new clinical trials.

Another source for cell therapies is represented by directly reprogrammed somatic cells which can be used to make DA neurons.

Research question/significance:
My thesis work focuses on studying and controlling the functional properties of different types of reprogrammed neurons, in particular their electrical activity, in order to assess their possible restorative role.

Margarita Chumarina - Induced pluripotent stem cells as a tool to model Parkinson’s Disease

Time: Tuesday, June 12th, at 09:15
Place: Dora Jacobsohn D1513c
Title: Induced pluripotent stem cells as a tool to model Parkinson’s Disease
Supervisor: Laurent Roybon
Co-supervisors: Tomas Deierborg, Gunnar Gouras and Yuriy Pomeshchik
Opponents: Edgar Pera and Marco Ledri
Parkinson’s disease (PD) is the most prevalent movement disorder, characterized by death of dopaminergic (DA) neurons; there is currently no cure available for PD, only symptomatic treatments exist. Predominantly, PD is an idiopathic disease, however there are about 10% of PD cases that are familial (fPD). The identification of PD-linked genes and their physiological roles greatly improved our understanding of PD pathogenesis, but at the same time made PD even more heterogenous in terms of aetiology, hindering the search for a cure. But with recent advances in the field of stem cell research, particularly the ability to obtain patient-specific induced pluripotent cells (iPSCs), it is now possible to generate  DA-enriched cultures from iPSCs with different PD backgrounds while patients are still alive. This allows investigating early cellular mechanisms and the contribution of different genetic variations to the disease and how they influence PD pathogenesis. Therefore, our first goal was to generate iPSCs from patients with different genetic disease backgrounds, including familial and sporadic PD. 
Many of the lines that we generated were published (Holmqvist et al., ‘Creation of a library of induced pluripotent stem cells from Parkinsonian patients’, NPJ Parkinsons Dis, 2016). New lines are constantly being reprogrammed and also include variations in the mitochondria DNA polymerase gene POLG1 and the SNCA gene encoding for alpha synuclein, a protein known to  aggregate in PD. Our next step will be to examine mitochondrial dysfunction and protein aggregation in neural cells derived from iPSCs. To better examine PD pathogenesis in DA neurons, we also have begun to generate reporter lines allowing to purify midbrain dopaminergic neurons for omic studies. These lines will also be useful to perform co-culture studies with PD iPSC-derived glia to examine the neuron-glia crosstalk in PD pathogenesis. We hope that our work will improve our understanding of the underlying mechanisms of PD and help identify novel targets for therapeutic intervention.

Yiyi Yang – Experimental Neuroinflammation Laboratory

Time: Monday May 14, at 15:15
Place: BMC I 1345
Title: Microglia function in neurodegenerative diseases
Supervisor: Tomas Deierborg 
Co-supervisors: Jia-Yi Li and Christopher Dunning

Opponents: Ilknur Ozen and Shorena Janelidze


Microglia are considered the main innate-immune cells of the central nervous system (CNS). They continuously survey their microenvironment and have the ability to interact with neurons to regulate their activity. Emerging evidence has shown that microglia are key causative players in neuroinflammation, which in turn is believed to play a major role in neurodegenerative diseases. A better understanding of the interactions between microglia and other cells in the brain is therefore needed in order to design therapies to ameliorate the detrimental effects of microglial reactions in brain diseases.

Different populations of microglia are characterized by various methods at both gene expression and protein levels using western blot, mass spectrometry and RNA sequencing. Lipopolysaccharide is used as a strong inflammatory stimulus for triggering activation of microglia in vitro. To further investigate the role of microglia under pathology, a stroke mouse model (permanent middle cerebral artery occlusion) and a transgenic mouse model of Alzheimer’s disease (5xFAD) are used in the study. Multiple ELISA is performed to determine different levels of inflammatory cytokines in CNS and peripheral. Flow cytometry is applied to define and sort out specific phenotypes of microglia in vitro and in vivo. Further analysis is achieved by using histological methods to evaluate how microglia affect the progression of pathology. Bioinformatic analysis is carried out to elucidate interaction of microglia between other cells as well as involved signaling pathways.

Preliminary results
We have demonstrated altered extracellular vesicles (EVs) production in BV2 microglial cells and altered cytokine levels and protein composition carried by EVs in response to LPS challenge. Importantly, we showed a distinct profile of proteins found in EVs released from LPS treated cells compared to control. We also found JAK/STAT, p38 MAPK and Interleukin pathways affected in microglial cells before amyloid plaque deposition in our 5xFAD mouse model. Therefore we pointed out early inflammatory changes in microglial cells occurred even before the accumulation of Aβ.

Our findings provide new insights into the potential roles of microglia that could be related to the pathogenesis in neuroinflammatory diseases.

Anders Wahlbom - Neural Basis of Sensorimotor Control

Time: May 9, at 11:00
Place: fikarummet på F10
Title: Widespread sensorimotor processing: its support by thalamocortical interactions
Supervisors: Henrik Jörntell and Fredrik Bengtsson
Opponents: Anders Rasmussen and Germund Hesslow

Widespread sensorimotor processing: its support by thalamocortical interactions

Background: How the brain processes information is still largely unknown to us. The reigning theory for the past 200 years is based on a hierarchical information process with each part of the cortex having a specific dedicated function. This view has however become increasingly questioned during the past decades, with numerous models trying to explain how the brain processes information arising. The presented PhD project aims to investigate one of these hypotheses, that the brain’s information processes are widely distributed across the neocortex.

Method: Neocortical and thalamic data is collected using various methods in anesthetized rodent models. At the single neuron level in vivo patch clamp is used in loose patch configuration, in the current clamp mode. It’s used to record the action potentials and local field potentials generated by a neuron and its immediate surroundings as a response to a predetermined set of intracutaneous electrotactile stimulation patterns. The neuronal response is recorded in various locations, and to both contralateral and ipsilateral stimulation, in both healthy subjects and those where a stroke model is used to induce functional deficits. Further analysis is performed using histological methods to validate the recording locations and the effect of the stroke.

Preliminary results: In summary our findings indicate that information processing does seem to happen in a widely distributed manner where the state of the entire neocortex is relevant for each process, rather than in the classical hierarchical manner. We’ve shown that individual neurons are able to decode information from contra- and ipsilateral input at comparable levels and that acute stroke causes widespread impairments in the tactile information processing of neurons considered anatomically far away from the area damaged by stroke.

Significance: All neurological diseases and deficits can be described as disruptions in how the brain processes information. The presented project looks at how the brain processes information at a very high level of detail and aim to give us an improved understanding of these processes and how they are disrupted by disease, thus improving our ability to understand the brain and treat its diseases.

Nishant Narayanan Vaikath, Neural Plasticity and Repair group
Time: Thursday, March 22nd, at 13:00
Place: BMC I1345
Title: Development of monoclonal antibodies specifically against different forms of alpha-synuclein as new tools for diagnostic and therapy in synucleinopathies.
Supervisors: Jia-Yi Li and Omar M El-Agnaf
Opponents: Karsten Ruscher (IKVL) and Christian Hansen (EMV)

Development of monoclonal antibodies specifically against different forms of alpha-synuclein as new tools for diagnostic and therapy in synucleinopathies.

Synucleinopathies including Parkinson’s disease (PD), dementia with Lewy bodies (DLB) and multiple system atrophy (MSA) are characterized by the abnormal accumulation of insoluble alpha-synuclein (α-syn) aggregates in the brain. Detection of these pathologic lesions in synucleinopathies has relied immensely on the use of α-syn antibodies, majority of which recognize different forms of α-syn. Recent data implicate that prefibrillar, oligomeric intermediates formed during aggregation as the toxic species than mature fibrils. Hence, developing tools such as antibodies against specific α-syn conformations selectively targeting neurotoxic forms would lead to better understanding of the pathogenesis of synucleinopathies.

Methods and Results
We generated specific monoclonal antibodies against wide array of α-syn species, namely oligomeric-, phosphorylated S129- and total- α-syn (t-, o- and p-S129- α-syn). The antibodies were then characterized extensively for specificity and affinity by various biochemical and immunohistochemical analysis. Initially, to explore the use of α-syn species as candidate biomarkers for PD these antibodies were employed to develop highly specific ELISA assays to quantify α-syn species in biological samples. The utility of the assays was verified in CSF samples from 46 PD patients and 48 age-matched healthy controls. The discriminating power of combining multiple CSF α-syn species with classical Alzheimer’s disease biomarkers were also assessed. The results revealed that combination of CSF o-/t-α-syn, p-S129-α-syn and p-tau provided the best fitting predictive model for discriminating PD patients. Thereafter, the assay systems were also used for measuring t-, o- or p-S129-α-syn in CSF from the longitudinal Deprenyl and Tocopherol Antioxidative Therapy for Parkinsonism (DATATOP) study cohort. The results showed that CSF α-syn species have a dynamic pattern along the course of the disease, supporting their possible role as progression biomarkers for PD and their link with PD clinical phenotypes. We have also sequentially extracted soluble and insoluble/aggregated α-syn from the post-mortem brain tissues form PD, DLB and AD cases using buffers with increasing detergent concentrations and compared with control samples. The results revealed that soluble non-phosphorylated o-α-syn was the most dominant species in the aqueous fraction of DLB, PD and AD brain lysates compared to control.

The antibodies portrayed herein represent a useful tool for research, biomarkers development, diagnosis and even immunotherapy for synucleinopathies.

Oktawia Nilsson, Medical Protein Science group
Time: Wednesday, March 7th at 13.00
Place: BMC building I (room 1341)
Title: Apolipoproteins in glucose and lipid metabolism
Supervisors: Jens Lagerstedt and Anna Blom
Opponents: Malin Fex (IKVM) and Olga Göransson (EMV)

Apolipoproteins in glucose and lipid metabolism

Background- Apolipoprotein A-I (ApoA-I) is the main protein component of high-density lipoprotein (HDL), thus it is an important carrier of cholesterol and lipids in blood circulation. The atheroprotective property of ApoA-I is therefore the most well-known function of this protein. The presented PhD project investigates lesser explored ApoA-I-mediated improvement in glucose control thus serving as a potential candidate for type 2 diabetes treatment (T2D). In addition, we research how structural changes in various ApoA-I variants can be linked to their atheroprotective or amyloidogenic properties.

Research question/Method- Functional and microscopic approaches are carried out to dissect the mechanisms behind ApoA-I-dependent increase in insulin secretion. These involve insulin secretion assay using rodent models, isolated pancreatic islets and clonal beta-cells, protein expression analysis, as well as confocal and electron microscopy techniques. Additionally, alteration of ApoA-I structure and functionality after glycation events has been researched. This includes cholesterol efflux from macrophages, muscle glucose uptake, insulin secretion and lipid clearance assay.  Protein secondary structure distribution in different ApoA-I variants as well as glycation-modified protein was measured with the use Synchrotron Radiation Circular Dichroism (SRCD) spectroscopy.

Preliminary results- A novel function for ApoA-I has been identified, i.e., its ability to prime beta-cells to increase glucose-stimulated insulin secretion. Proposed mechanisms include increased concentration of insulin granules close to the cell membrane, increased processing of proinsulin and enhanced insulin synthesis. Glycation of ApoA-I has been shown to have a negative effect on protein’s functionality. Secondary structure and functionality measurements of different ApoA-I variants revealed that position of the mutation in the ApoA-I sequence differently affects the molecular structure and the stability of the formed HDL

Significance- The presented data make an advancement in the understanding of ApoA-I’s action on insulin secretion and glucose control, which is important while looking for ApoA-I-based formulation for T2D treatment with added anti-CVD effect. Moreover, exploring the structural plasticity and pathogenesis of amyloidogenic ApoA-I variants is important for developing future treatments.

Joel Sjöbom
Motor coding in cortico-basal ganglia networks
Time: 26/1 kl. 10.00
Place: E24 på Medicon Village – byggnad MV 404
Supervisor: Per Petersson
Co-supervisors: Martin Garwicz, Pär Halje and Ulrike Richter
Opponents: Dr. Christian Balkenius and Dr. Henrik Jörntell


Carla Azevedo
Modeling alpha-synuclein pathology using stem cell-based models
Time: December 4, 10:00
Place: BMC I1345
Supervisor: Laurent Roybon, Lund University
Co-supervisor: Gunnar Gouras, Lund University and Tomas Deierborg, Lund university.
Opponents: Iben Lundgaard, Lund University and Filipe Pereira, Lund university

Marie Sjögren
Energy metabolism as a target for new treatment strategies in Huntington's disease
Time: October 27,  10:00
Place: BMC I1342
Supervisor: Maria Björkqvist
Co-supervisor: Nils Wierup
Opponents: Malin Fex and Rachel Cheong

Isak Martinsson
Investigating synaptic roles of Bera-amyloid and APP
Thursday October 26 at 9:00 am, BMC, I 1308
Supervisor: Prof. Gunnar Gouras, Lund University
Co-supervisor: Prof. Oskar Hansson, Lund University
Opponents: Dr. Tim Fieblinger, Lund University and Dr. Tomas Deierborg, Lund University