Martin Dichgans – Translational Stroke and Dementia Research

We are interested in the molecular, cellular, and physiological mechanisms of stroke and cerebrovascular disease. We use genetic approaches to identify novel risk genes and explore their functional role in vitro and in vivo using genome-editing, proteomics, and imaging technology. We are particularly interested in cerebral small vessel disease and large artery atherosclerotic stroke.

A major starting point of our work are patients with stroke that are examined through prospective clinical studies along with healthy individuals. We apply genetic (GWAS and sequencing) and other omics techniques to identify novel targets and pathways relevant to specific mechanistically defined stroke subtypes.

We use this information to explore relationships with informative intermediate (e.g. vascular, metabolic) and related phenotypes (e.g. coronary artery disease). We have established genetic mouse models for cerebral small vessel disease (SVD) derived from the genetic discoveries (e.g. HtrA1, Col4A1, Foxf2) and use these models to identify and characterize key molecular (e.g. TGF-ß signaling) and physiological (e.g. blood-brain-barrier) pathways and cellular targets (in particular vascular endothelial cells and brain pericytes) relevant to the pathogenesis of SVD.

Another area increasingly moving into the focus of our research is atherosclerosis. We in collaboration with others recently identified several risk loci for large artery stroke and are currently exploring the role of relevant genes (e.g. HDAC9, TSPAN2) in atherogenesis and vascular injury (-> see here for details).

Yaw Asare

I joined the Dichgans lab in September 2014 after my PhD and a short postdoc stay in RWTH Aachen University (BernhagenLab). Building on my expertise in vascular signaling, the crosstalk between epigenetic regulatory mechanisms and the NFkB pathway driving vascular inflammation is a major research focus. Several in vivo mouse models of atherosclerosis and vascular injury are flanked by in vitro mechanistic studies to decifer the role of HDAC9 in vascular inflammation. We further explore the inhibition of HDAC9 as a therapeutic strategy to reduce vascular inflammation, which may serve as a target for interventional studies in humans.

Nathalie Beaufort, PostDoc

I grew up and studied in France, and obtained my doctoral thesis in Physiology and Physiopathology in 2005 at University Paris 6. After post-doctoral experiences in France and Germany, I joined the group of Martin Dichgans at the ISD in 2010 as a research associate. My work focusses on the biochemistry, cellular and molecular biology of cerebral small vessel disease with an emphasis on CARASIL, an inherited disorder caused by loss-of-function mutations targeting the HTRA1 protease. To explore the pathomechanisms underlying CARASIL and develop innovative repair strategies, I combine the analysis of recombinant proteins, patient-derived primary cells and mouse tissues.

Marios Georgakis, PhD

Originally from Greece, I have studied medicine at the University of Athens (graduated in 2015) and completed Master studies in Neurosciences at the same University (2017). After an experience for 4 years as a research fellow in the field of epidemiology in Athens, I joined Martin Dichgans’ group at the ISD in 2017 as a PhD student of the Graduate School of Systemic Neurosciences. Here, I work on the genetic and clinical epidemiology of cerebrovascular disease. My main goal is to use genetic data to identify causal risk factors and novel therapeutic targets for stroke and cerebral small vessel disease. My research interests further lie in determining the causes and predictors of cognitive decline after stroke.

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Judit Gonzales Gallego, PhD student

I am born in Spain and obtained my BSc in biochemistry from the Autonomous University of Barcelona. After completing my bachelors degree, I worked for one year at the Center of Neurobiology of Hamburg University with Dr. Marina Mikhaylova in protein neuronal transport. Currently, I'm a student in the Graduate School of Systemic Neuroscience (GSN) and after performing a research internship in PaquetLab on CRISPR/Cas9 genome editing I decided to join the ISD in October 2018 for a PhD project in neurovascular disorders co-supervised by Martin Dichgans and Dominik Paquet.

Anna Kopczak, clinician scientist

Originally from Poland, I grew up in Germany and studied medicine at the University Duisburg-Essen and at the LMU. During my clinical residency in neurology, I was involved in clinical studies dealing with hormonal disturbances after brain damage such as traumatic brain injury and stroke. From 2011 to 2016, I continued my clinical education and improved my scientific knowledge at the Max-Planck-Institute of Psychiatry in Munich. With my clinical expertise as a neurologist and my experiences in clinical research, I joined the group of Martin Dichgans in April 2016 as a clinician scientist. The focus of my research are clinical studies to improve our understanding of stroke mechanisms and to optimize treatment of cerebrovascular diseases.

Rainer Malik, PostDoc

Originally from Austria, I studied molecular biology with a focus on computational biology and protein structure prediction at the University of Salzburg. As an early adopter in the bioinformatics field, I changed subject to further strengthen my computational knowledge and obtained my PhD in Computer Science at the Universiteit Utrecht in 2006. After a first PostDoc analyzing cell-cycle dependent proteomics data (Prof. Nigg, MPI Biochemistry, Martinsried), I joined the ISD at the very beginning in 2009 to analyze large-scale OMICS data. Here, over the last years, we have led or participated in all major genetic studies of stroke and stroke-related comorbidities. Through extensive international collaborations (ISGC, METASTROKE, MEGASTROKE) we strive to translate genetic, genomic and other OMICS findings to animal models and subsequently to the clinic.

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Melanie Schneider, technical assistant

I finished my education as a medical technical assistant in 2005 and immediately started working with Professor Martin Dichgans. I take care of organizational issues to all groups, place orders and do many histology works for my group members (e. g. preparing and cutting tissue, do staining’s, microscopy and sometimes evaluations). I am currently involved in projects aimed at identifying the mechanism underlying proatherogenic role of HDAC9 and exploring the therapeutic potential of HDAC9 inhibition for atheroprotection.

Dr. Katalin Todorov-Völgyi

Originally from Hungary, I studied biology and obtained my PhD in 2016 at Eötvös Loránd University in Budapest in molecular neurobiology, focusing on the early molecular changes in Alzheimer’s disease and Vascular Dementia. I joined the Dichgans lab as a Postdoc in February 2017. My research aims to reveal the molecular, cellular and physiological mechanisms of cerebral small vessel disease (SVD), stroke and vascular cognitive impairment. For these purposes, I use a genetic mouse model with Foxf2 deficiency, which was identified as a novel risk gene in SVD and stroke in recent Genome-Wide Association Studies. To understand the role of Foxf2 and identify new molecular targets in SVD patomechanisms, I combine omics technologies, microscopy, image analysis, and behavior assessments on mouse models. Outside the lab, I like photography, hiking, traveling and exploring new places.

Simon Frerich, PhD student

I joined the Dichgans Lab as a PhD student in bioinformatics in 2020. Currently, I am using spatial transcriptomic data to identify stroke-related focal processes in the brain. Prior to this, I followed up on our stroke GWAS findings, mainly by leading a Mendelian Randomisation analysis of cardiac risk factors for stroke. I am also part of the Graduate School of Systemic Neurosciences at LMU Munich. Prior to my PhD, I engaged in a research internship with Eric Westman at Karolinska Institute. I hold an MSc from Imperial College London and a BSc from TU Dresden with a stay at NTNU. Besides my PhD, I am frequently found on the way to an Alpine summit.

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Christina Schlegl, MD student

I joined the Dichgans lab in November 2020 as a medical student after completing my first states examination at the LMU in 2019 and proceeding with my studies at the TUM. Building on previous work in this research group my primary research focus is further ascertaining the role of HDAC9 in vascular inflammation. Genome-wide human association studies have shown the translational significance of HDAC9 in atherogenic inflammation and pathologies such as ischemic stroke. We thus aim to determine underlying molecular mechanisms and hope to contribute to developing treatments for ameliorating the impact of atherosclerosis on society.

Luka Zivkovic, MD student

Born and raised in Munich, I began studying medicine at LMU in 2016. In 2019, I joined the Dichgans Lab for my MD thesis project. My work revolves around how macrophages contribute to disease initiation and progression in atherosclerotic pathologies like ischemic stroke and coronary artery disease. Specifically, we are investigating mechanistic aspects of proinflammatory cell signaling, for instance the interaction between HDAC9 and the NF-κB pathway, a key regulator of proinflammatory gene expression. I am further interested in the role of small chemokines in endothelial inflammation and how they can be used in therapeutic approaches. My primary goal is to contribute to the identification of novel, promising targets for the treatment of atherosclerosis. Outside of lab and lecture hall I enjoy cooking in good company and supporting my local basketball team.