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.
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.