Wallenberg Molecular Medicine Fellow - Diabetes
Insulin signalling has a role in modulating brain function, namely through control of metabolism and synaptic plasticity, and its deterioration occurs in neurodegenerative disorders, such as Alzheimer’s disease (AD), and in diabetes mellitus.
We are mainly investigating the coupling between brain metabolism and function, and its deregulation in diabetes, as well as contributing to identify strategies for rescuing brain metabolic regulation in diabetes. Our research is focused on the hippocampus and cortex, which are brain regions involved in cognition, and on the hypothalamus, which has a major role in whole-body energy balance. Notably, since metabolic alterations are likely early events in the process of neurodegeneration, this line of research may provide early biomarkers to identify encephalopathy prior to severe loss of brain functions in diabetes patients.
Wallenberg Molecular Medicine Fellow – Respiratory System
Over three million people die each year and over 60 million people suffer worldwide from chronic lung diseases (CLDs). At present, there is no cure for CLDs, including chronic obstructive pulmonary disease (COPD), pulmonary hypertension, and pulmonary fibrosis. Lung transplantation is the only option at end-stage disease and is further complicated by shortage in organs available for transplantation and low efficacy. Five-year survival rate has remained at 50% for the last decade. New options are desperately needed for these patients.
Our lab focuses on understanding the role of the extracellular environment for endogenous and exogenous lung tissue regeneration in healthy and diseased lung. In particular, our work focuses on the design and use of biologic and synthetic scaffolds to bioengineer new lung tissue for transplantation. We further aim to build new models of human lung tissue to reduce animal usage, better understand how regeneration processes are deranged in CLDs, and for use as drug discovery and therapeutic screening platforms.
Wallenberg Molecular Medicine Fellow – Hematopoietic System
The focus of our lab is to understand the molecular determinants underlying cellular reprogramming and hematopoietic specification. Cellular reprogramming can be achieved experimentally in different ways, including nuclear transfer, cell fusion or expression of transcription factors. The emergent ability to reprogram differentiated cells into desired hematopoietic cell-types is opening avenues to the discovery of new therapies for immune and blood diseases.
The goals of my laboratory are a) to understand at the molecular level how hematopoietic cellular identities are specified employing cellular reprogramming logic and b) to use this knowledge to manipulate genes and pathways that ultimately may allow the generation of patient-specific hematopoietic cells for regenerative medicine and immunotherapy.
Wallenberg Molecular Medicine Fellow – Cardiovascular System
Cardiovascular disease such as heart attack, stroke, and peripheral vascular disease, is the number-one health problem in the world. Despite remarkable progress in diagnosis and prevention, cardiovascular diseases cause disability and death at an astounding rate. The best opportunities to develop and implement new strategies for preventing and treating cardiovascular disease lie in the understanding of its underlying mechanisms.
Thus far, our earlier work provides ample evidence that S1P plays a key role in immune cell recruitment, cytokine production and vascular tone regulation during experimental hypertension and heart failure. Therefore, we strongly believe that S1P’s signalling axis will prove an attractive therapeutic target for cardiovascular complications.
Our research aims to isolate novel therapeutic targets that effectively prevent and most importantly, also reverse complications mediated by cardiovascular risk factors such as hypertension. Specifically, we are interested in sphingosine-1-phosphate (S1P) signalling and its role in the regulation of the vascular and the immune system.
- More information about Anja Meissner in Lund University Research Portal
- Read about Gustav Smith and Anja Meissner in LUM magasin nr 6, 2017
Wallenberg Molecular Medicine Clinical Researcher – Diabetes
The core of our research is to bridge the surprisingly under-explored gap between the “omics” of epidemiology (e.g. genomics, metabolomics and proteomics) and biological and clinical function. Thus, a major component our research is to enhance the understanding of causes to progressing diabetes and cardiovascular disease (CVD) where we invest large efforts in metabolomics and proteomics. However, a central issue is that we do not stop at finding metabolites/proteins and metabolomics/proteomic patterns associated with risk of progressing disease, but we also examine the importance of genetic predisposition behind such relationship to find causal association and we also aim to explore the underlying mechanisms (by in vivo/vitro experiments and even human trials if applicable).
Here we have already discovered two novel candidates in the amino acids isoleucine, phenylalanine, and tyrosine but also in dimethylglycine, which will be further tested to shed light on the biochemical underlying mechanisms. It is conceivable to assume that our causality assessment of biomarkers of disease will provide guidance on whether or not drug development targeted at the biomarker in question is worthy to pursue. Apart from this, we will generate substantial clinical value by accurately describing the utility of all known common and rare genetic diabetes and CVD susceptibility variants as well as metabolites and proteins in clinical diabetes and CVD risk prediction and risk stratification in some of the largest population based cohorts in the world.
Wallenberg Molecular Medicine Fellow – Nervous System
Despite the brain’s high level of metabolic activity the central nervous system (CNS) does not contain any lymphatic vessels. The cerebrospinal fluid (CSF) is driven into peri-vascular spaces where exchange of solutes takes place and this mediates brain-wide clearance. The peri-vascular bulk flow system was named the glia-lymphatic (glymphatic) system due to the crucial role of astrocytes’ aquaporin 4 (AQP4) water channels. The glymphatic system is akin to the lymphatic system and also connects with the conventional lymphatic system upon drainage from the CNS. Due to the drainage to lymph nodes, it is believed that the glymphatic system is important for CNS immune function.
Our lab is interested in the glymphatic system due to its function as a macroscopic clearance system. Among specific research topics at the Lundgaard laboratory is the role of the glymphatic system in neurodegenerative diseases, such as Parkinson’s disease, and in CNS immunity including the autoimmune disease multiple sclerosis.
Wallenberg Molecular Medicine Clinical Researcher – Cardiovascular System
Heart failure is the end-stage of all heart disease, characterized by inability of the heart to maintain sufficient output of blood for the demands of the body, and arguably constitutes the major unmet clinical need in cardiovascular medicine today.
In our research, we aim to improve understanding of the causes and mechanisms underlying heart failure, to identify novel therapeutic targets and facilitate individually tailored treatment strategies. My research group applies and integrates a range of omics tools to large cohorts with blood and heart tissues from heart failure cases, recipients of heart transplants and mechanical circulatory support, and the general population.
- More information about Gustav Smith in Lund University Research Portal
- Read about Gustav Smith and Anja Meissner in LUM magasin nr 6, 2017
Wallenberg Molecular Medicine Clinical Researcher – Nervous System
Our ultimate research vision is to discover, develop and implement novel neuroprotective and neurorestorative therapies for neurological disorders such as Parkinson’s disease, Huntington’s disease and stroke. My group works with translational research that is tightly linked to clinical research questions.
Our experimental focus is to understand neurovascular disease mechanisms. We examine the dysfunction of the neurovascular unit with a special focus on pericytes as key players in inflammation and neurodegeneration and as potential target cells for brain repair. We apply in vitro and in vivo disease modeling and utilize different patient samples.
We aim to identify new target cells facilitating brain repair and characterize novel restorative molecules for the above brain disorders. At the same time I am actively involved in clinical research with the focus on clinical implementation of stem cell and different growth factor therapies for Parkinson’s disease.
Wallenberg Molecular Medicine Clinical Researcher – Hematopoietic System
Our main goal is to improve outcome for the painful and fatal tumor disease, multiple myeloma (MM). To do this we will pursue three lines of research; i) use investigator initiated clinical trials to test prevention strategies and ii) to test new drug combinations and iii) investigate phagocyte subsets and functions during treatment and progression of MM. If successfull, this project will i) show that elimination of common subclinical infections could abrogate the MGUS clone and possibly prevent or decrease the risk of progression into MM ii) improve MM treatment and iii) gain knowledge of how phagocytes contribute to progression of MM. This will be of importance in a near future during the development of antibody based treatments against MM which depend on phagocyte immune functions, this could also lead to completely new treatment strategies targeting the MM supporting bone marrow miliue.
Cornelis Jan Pronk
Wallenberg Molecular Medicine Clinical Researcher – Hematopoietic System
Hematopoietic cell transplantation (HCT) is often considered a last treatment resort for a number of serious diseases. At the Pediatrics Department in Lund, parental donors are often used in such setting, referred to as haploidentical (haplo-) HCT. In our research, we aim to study a number issues concerning haplo-HCT with the overall aim to increase efficacy and decrease treatment related complications.
First, in Haplo-HCT cells are transferred across large age boundaries; does this come at a price? Therefore, we study aging within our blood cell system, with a focus on hematopoietic stem cells. We study the mechanisms that drive these changes and aim to evaluate if haplo-HCT recipients present with signs a premature hematopoietic aging?
Second, as parental donors are only 50% HLA-identical, these children are at risk for graft-versus-host disease, whilst potentially benefitting from graft-versus-tumor actions. Future work will detail clinical outcome of such pediatric haplo-HCTs. Further, we will use a murine model to study hematological regeneration following haplo-HCT and evaluate how extended graft manipulation impacts graf-versus-tumor actions.
Sandra Lindstedt Ingemansson
Wallenberg Molecular Medicine Clinical Researcher – Respiratory System
A considerable problem in lung transplantation is the shortage of donor lungs, and has resulted in deaths on the waiting list. A lot of improvements have been done considering donor management and organ preservation, still only approximately 20% of potential candidate lungs for transplantation are being transplanted. In addition chronic rejection - chronic lung allograft dysfunction (CLAD), primary graft dysfunction (PGD), and infections remains the major barrier to long-term success. The primary cause of death after LTx is CLAD. The development of CLAD is rare in the first year after LTx, but the rate increases quickly with cumulative incidence reported to be as high as 40 % to 80 % within the first five years. Bronchiolitis obliterans (BO) is the pathologic pattern of injury most commonly seen in lung transplant recipients with progressive loss of lung function. Distribution is often patchy in the lung parenchyma and is difficult to detect with trans-bronchial biopsy. Early CLAD diagnose detection, often increases the chance of survival, since early treatment might inhibit the development of CLAD, therefore it is a great need for finding new none invasive methods for early detection of CLAD but also for detection of PGD.
Our research group has a long-standing interest in lung transplantation (LTx) and the research focus has been on two main challenges in LTx, organ shortage and organ rejection. Our research group has focused on optimizing and improving marginal donor lungs using ex vivo lung perfusion (EVLP) on brain dead donors but also by using donation after cardio-circulatory determination of death (DCD) donors in the urge to increase the donor pole. Our research group has also focusing on finding early biomarkers for CLAD and PGD in exhaled air.
Wallenberg Molecular Medicine Clinical Researcher – Medical Imaging
Positron Emission Tomography with Computed Tomography (PET-CT) is a fast growing imaging modality and an important part of the evaluation of patients with cancer for assessment of the primary tumour, for lymph node staging and for detection of metastases. It can also be used for evaluation of inflammatory/infectious diseases, cardiac diseases and dementia. Recently, a novel generation of digital PET-CT scanners were developed, that will hopefully lead to improved diagnostic capacity, but this needs to be verified in studies. Current imaging techniques, including PET-CT, are challenged by time consuming manual analysis, lack of quantification and clinical validation. Objectively measured imaging biomarkers that reliably quantify the PET-tracer activity would therefore be important.
Our research group want to realize the true potential of PET-CT through two different projects: 1) To fully validate the new digital PET-CT scanners and 2) To use new artificial intelligence algorithms to develop novel PET-CT imaging biomarkers as indicators of prognosis and treatment efficacy in patients with cancer. Validated imaging biomarkers could transform future clinical care, clinical trials and drug discovery for cancer.
Wallenberg Molecular Medicine Fellow – Musculoskeletal System
Bone is a complex Organ providing structural and mechanical support of our body, but also consisting in our principal hematopoietic center. The formation of our bones is tightly and timely orchestrated, involving stages of cartilage, vasculature, bone and bone marrow establishment. My lab aims at compiling human-specific knowledge on how these tissues form, interact and regenerate at an organ scale, toward the development of innovative regenerative therapies. Precisely, we exploit Bone organogenesis as a paradigm to decipher the driving cellular and molecular mechanisms. Toward this objective, we develop cutting-edge in vitro / in vivo models offering the custom design of human skeletal tissues & organs:
(i) The in vivo formation of human bone organs
(ii) The in vitro engineering of bone marrow models in 3D culture systems
(iii) The design of grafts for skeletal tissue regeneration using death-inducible mesenchymal lines
Clinical implications of our research run from the repair of bone and cartilage defects, the expansion/differentiation of human blood cells for transplantation, and the screening of drugs for blood cancer treatment.
Wallenberg Molecular Medicine Fellow – Cancer
Cells in our body exist not only in a diverse biochemical environment but also in a highly dynamic and complex mechanical environment such as blood flow, muscle contraction-relaxation, stiffness of different organs and the extra-cellular matrix. Starting from embryogenesis, tissue development and differentiation to immune, cardiovascular, musculoskeletal and brain function, the mechanical environment plays an important role in all these processes. Not surprisingly, breakdown or mis-regulation of the interactions between cellular functions and the mechanical environment results in many pathologies including disease progression in a number of different cancers.
The goal of my lab is to understand the cellular and molecular mechanisms by which cells interact with their mechanical environment and how mis-regulation of these interactions results in tumor progression and metastasis. We are primarily focused but not limited to investigating the effect of this environment on the process of cell migration and cancer metastasis. Our approach is to develop and use quantitative microscopy techniques as well as tools from engineering and physics to build in-vitro cancer models and extend knowledge gained from these fundamental mechanistic studies to more clinically relevant cancer models.
Wallenberg Molecular Medicine Clinical Researcher – Musculoskeletal System
Can children get rheumatic joint disease? Is it a life-long disease? Does my child really need all these drugs!!! These are the questions we hear every week when meeting families to children with newly diagnosed inflammatory joint disease.
To get a chronic disease will have a major impact on your day-to-day life and suddenly you are different… you need medications, repeated doctors’ visits… and you have pain.
-Why did I get this?!
In our research group, we try to answer these questions that patients and parents ask every day. We investigate the long-term prognosis and risk of comorbidities in children with inflammatory joint disease as well as the inflammatory pattern in the joint of these children. We will try to manipulate the immune-cells to switch from a pro-inflammatory state to a state of resolution and homeostasis.
Our overall aim is to improve the care of children with rheumatic diseases.
Wallenberg Molecular Medicine Clinical Researcher – Nervous System with Emphasis on Plasticity and Function
Manual daily activities require interactions between the peripheral and central nervous systems, which is obvious when an individual suffers a nerve injury, a neuropathy, or a stroke with subsequent impaired hand function. Hand amputees often use a prosthesis, which lack sensory feedback allowing only simple gripping.
This project has three aims: 1/ mapping cerebral plasticity, 2/ development of treatment strategies using guided plasticity for patients with nerve injury, neuropathy and stroke, and 3/ development of systems for sensory feedback and motor control of hand prosthesis.
The effects of the described conditions are examined in the peripheral nerve and in the brain, using advanced high (3T) and ultra-high (7T) magnetic resonance imaging (MRI) techniques, neurophysiology and clinical tests for development of treatment strategies, where the dynamic capacity of the brain, i.e plasticity, is guided to improve hand functions.
A modality-matched sensory feedback applicable in existing hand prosthesis is created with a new approach to control prosthetic hands. Control algorithms, based on intramuscular EMG or high-density surface EMG, are used to control modern, multi-degree of freedom, prosthetic hands.
Wallenberg Molecular Medicine Clinical Researcher – Cancer
Despite recent advances, there is still a substantial unmet medical need for novel cancer therapeutics. A new class of pharmacological compounds, based on RNA, open up new possibilities to specifically target numerous cancer cell vulnerabilities. Cytosolic delivery of the macromolecular RNA molecules is the biggest hurdle to translate these molecules into clinically useful drugs. Still, a few RNA based drugs have entered clinical use and delivery to certain human tissues, notably the liver and CNS, is possible. However, to reach other tissues, and in particular tumors, the delivery process has to be improved significantly.
In our lab we have two main focus areas: First, we develop methods to study the process of cytosolic delivery of RNA. In particular, we have developed high resolution microscopy methods to study RNA delivery in living cells. Second, based on the insights from these studies we are developing novel strategies to enhance RNA delivery to tumors. These efforts have the potential to specifically turn off driving cancer genes and ultimately halt disease progression.
Wallenberg Molecular Medicine Clinical Researcher – Medical Imaging
Imaging has a fundamental importance in medicine as it allows for non-invasive examination of both morphology and function. For translational science, imaging is a powerful tool, as the same imaging techniques can be used to evaluate treatment response in pre-clinical animal models, early human experiments, and lastly in large clinical studies. Medical image analysis is a research discipline where with help of computations one can identify and delimit structures in image volumes to quantify biological or physiological parameters. Image processing is a prerequisite to create objective quantitative analysis methods for diagnosis, clinical or preclinical research were the data comes from medical imaging.
In our research we develop novel methods and tools to process images. One research direction is towards full automation using machine learning to handle large study cohorts with tens of thousands of patients. Another research direction is precision medicine where imaging and image processing are used to develop patient specific models for surgical planning, combined with mathematical models to predict and optimize the outcome of the surgery.
Wallenberg Molecular Medicine Fellow – Nervous System with Emphasis on Plasticity and Function
Alzheimer’s disease (AD) is a common neurodegenerative disease, which causes immense suffering for tens of millions of patients and their relatives, and huge financial burdens for societies worldwide. Despite intense research efforts, there is still no cure or disease-modifying treatment for AD. This is partly due to a lack of understanding of the earliest events in the disease, and how the different components of the disease cascade are linked together.
My research is focused on the earliest stages of AD. In particular, I am interested in understanding the mechanisms of beta-amyloid and tau accumulation, which are neuropathological hallmarks of AD. There are still many mysteries regarding why beta-amyloid and tau accumulate. For example, the accumulation appears to follow largely predictable spatiotemporal patterns, but why do these processes start? And what underlies the selective vulnerability in different brain regions? Another unsolved question is how beta-amyloid and tau are linked together. For example, beta-amyloid accumulation appears to be necessary for the detrimental spread of tau across the brain, but why? It is also not clear how beta-amyloid or tau actually cause injury to synapses and neurons. For example, how closely correlated are accumulation of beta-amyloid and tau with synaptic and neuronal loss? And what determines the variability in these correlations? Are there especially toxic forms of beta-amyloid or tau that are responsible for the injury, or are other components also necessary?
Being part of WCMM will help me to develop more advanced approaches to study these basic pathophysiological questions. I utilize a variety of experimental systems for my studies, including advanced biochemical and neuroimaging testing in human volunteers, genetic studies, and cell biology experiments. I am also interested in translating my findings into tools to manage brain injuries in general, including in other neurodegenerative diseases and brain injury after cardiac arrest.