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).
Duering M, Biessels GJ, Brodtmann A, Chen C, Cordonnier C, de Leeuw FE, Debette S, Frayne R, Jouvent E, Rost NS, Ter Telgte A, Al-Shahi Salman R, Backes WH, Bae HJ, Brown R, Chabriat H, De Luca A, deCarli C, Dewenter A, Doubal FN, Ewers M, Field TS, Ganesh A, Greenberg S, Helmer KG, Hilal S, Jochems ACC, Jokinen H, Kuijf H, Lam BYK, Lebenberg J, MacIntosh BJ, Maillard P, Mok VCT, Pantoni L, Rudilosso S, Satizabal CL, Schirmer MD, Schmidt R, Smith C, Staals J, Thrippleton MJ, van Veluw SJ, Vemuri P, Wang Y, Werring D, Zedde M, Akinyemi RO, Del Brutto OH, Markus HS, Zhu YC, Smith EE, Dichgans M, Wardlaw JM. Neuroimaging standards for research into small vessel disease-advances since 2013. Lancet Neurol. 2023 May 23:S1474-4422(23)00131-X. doi: 10.1016/S1474-4422(23)00131-X. Epub ahead of print.
Mishra A, Malik R, Hachiya T, Jürgenson T, Namba S, Posner DC, Kamanu FK, Koido M, Le Grand Q, Shi M, He Y, Georgakis MK, Caro I, Krebs K, Liaw YC, Vaura FC, Lin K, Winsvold BS, Srinivasasainagendra V, Parodi L, Bae HJ, Chauhan G, Chong MR, Tomppo L, Akinyemi R, (...) Riaz M, Simonsick EM, Kõrv J, França PHC, Zand R, Prasad K, Frikke-Schmidt R, de Leeuw FE, Liman T, Haeusler KG, Ruigrok YM, Heuschmann PU, Longstreth WT, Jung KJ, Bastarache L, Paré G, Damrauer SM, Chasman DI, Rotter JI, Anderson CD, Zwart JA, Niiranen TJ, Fornage M, Liaw YP, Seshadri S, Fernández-Cadenas I, Walters RG, Ruff CT, Owolabi MO, Huffman JE, Milani L, Kamatani Y, Dichgans M, Debette S. Stroke genetics informs drug discovery and risk prediction across ancestries. Nature. 2022 Sep 30. doi: 10.1038/s41586-022-05165-3. Epub ahead of print.
Markus HS, van Der Flier WM, Smith EE, Bath P, Biessels GJ, Briceno E, Brodtman A, Chabriat H, Chen C, de Leeuw FE, Egle M, Ganesh A, Georgakis MK, Gottesman RF, Kwon S, Launer L, Mok V, O'Brien J, Ottenhoff L, Pendlebury S, Richard E, Sachdev P, Schmidt R, Springer M, Tiedt S, Wardlaw JM, Verdelho A, Webb A, Werring D, Duering M, Levine D, Dichgans M. Framework for Clinical Trials in Cerebral Small Vessel Disease (FINESSE): A Review. JAMA Neurol. 2022 Aug 15. doi: 10.1001/jamaneurol.2022.2262. Epub ahead of print.
Georgakis MK, Fang R, Düring M, Wollenweber FA, Bode FJ, Stösser S, Kindlein C, Hermann P, Liman TG, Nolte CH, Kerti L, Ikenberg B, Bernkopf K, Poppert H, Glanz W, Perosa V, Janowitz D, Wagner M, Neumann K, Speck O, Dobisch L, Düzel E, Gesierich B, Dewenter A, Spottke A, Waegemann K, Görtler M, Wunderlich S, Endres M, Zerr I, Petzold G, Dichgans M; DEMDAS Investigators. Cerebral small vessel disease burden and cognitive and functional outcomes after stroke: A multicenter prospective cohort study. Alzheimers Dement. 2022 Jul 25. doi: 10.1002/alz.12744. Epub ahead of print.
Kopczak A, Schindler A, Sepp D, Bayer-Karpinska A, Malik R, Koch ML, Zeller J, Strecker C, Janowitz D, Wollenweber FA, Hempel JM, Boeckh-Behrens T, Cyran CC, Helck A, Harloff A, Ziemann U, Poli S, Poppert H, Saam T, Dichgans M. Complicated Carotid Artery Plaques and Risk of Recurrent Ischemic Stroke or TIA. J Am Coll Cardiol. 2022 Apr 27:S0735-1097(22)04687-3. doi: 10.1016/j.jacc.2022.03.376. Epub ahead of print.
Malik R, Beaufort N, Frerich S, Gesierich B, Georgakis MK, Rannikmäe K, Ferguson AC, Haffner C, Traylor M, Ehrmann M, Sudlow CLM, Dichgans M. Whole-exome sequencing reveals a role of HTRA1 and EGFL8 in brain white matter hyperintensities. Brain. 2021 Oct 22;144(9):2670-2682. doi: 10.1093/brain/awab253.
Georgakis MK, de Lemos JA, Ayers C, Wang B, Björkbacka H, Pana TA, Thorand B, Sun C, Fani L, Malik R, Dupuis J, Engström G, Orho-Melander M, Melander O, Boekholdt SM, Zierer A, Elhadad MA, Koenig W, Herder C, Hoogeveen RC, Kavousi M, Ballantyne CM, Peters A, Myint PK, Nilsson J, Benjamin EJ, Dichgans M. Association of Circulating Monocyte Chemoattractant Protein-1 Levels With Cardiovascular Mortality: A Meta-analysis of Population-Based Studies. JAMA Cardiol. 2021 May 1;6(5):587-592. doi: 10.1001/jamacardio.2020.5392.
Malik R, Georgakis MK, Neitzel J, Rannikmäe K, Ewers M, Seshadri S, Sudlow CLM, Dichgans M. Midlife vascular risk factors and risk of incident dementia: Longitudinal cohort and Mendelian randomization analyses in the UK Biobank. Alzheimers Dement. 2021 Sep;17(9):1422-1431. doi: 10.1002/alz.12320. Epub 2021 Mar 22.
Georgakis MK, Malik R, Li X, Gill D, Levin MG, Vy HMT, Judy R, Ritchie M, Verma SS; Regeneron Genetics Center, Nadkarni GN, Damrauer SM, Theodoratou E, Dichgans M. Genetically Downregulated Interleukin-6 Signaling Is Associated With a Favorable Cardiometabolic Profile: A Phenome-Wide Association Study. Circulation. 2021 Mar 16;143(11):1177-1180. doi: 10.1161/CIRCULATIONAHA.120.052604. Epub 2021 Mar 15.
Georgakis MK, de Lemos JA, Ayers C, Wang B, Björkbacka H, Pana TA, Thorand B, Sun C, Fani L, Malik R, Dupuis J, Engström G, Orho-Melander M, Melander O, Boekholdt SM, Zierer A, Elhadad MA, Koenig W, Herder C, Hoogeveen RC, Kavousi M, Ballantyne CM, Peters A, Myint PK, Nilsson J, Benjamin EJ, Dichgans M. Association of Circulating Monocyte Chemoattractant Protein-1 Levels With Cardiovascular Mortality: A Meta-analysis of Population-Based Studies. JAMA Cardiol. 2020 Nov 4. Epub ahead of print.
Kopczak A, Schindler A, Bayer-Karpinska A, Koch ML, Sepp D, Zeller J, Strecker C, Hempel JM, Yuan C, Malik R, Wollenweber FA, Boeckh-Behrens T, Cyran CC, Helck A, Harloff A, Ziemann U, Poli S, Poppert H, Dichgans M, Saam T. Complicated Carotid Artery Plaques as a Cause of Cryptogenic Stroke. J Am Coll Cardiol. 2020 Nov 10;76(19):2212-2222.
Asare Y, Campbell-James TA, Bokov Y, Yu LL, Prestel M, El Bounkari O, Roth S, Megens RT, Straub T, Thomas K, Yan G, Schneider M, Ziesch N, Tiedt S, Silvestre-Roig C, Braster Q, Huang Y, Schneider M, Malik R, Haffner C, Liesz A, Soehnlein O, Bernhagen J, Dichgans M. Histone Deacetylase 9 Activates IKK to Regulate Atherosclerotic Plaque Vulnerability. Circ Res. 2020 Jun 17. Epub ahead of print.
Georgakis MK, Malik R, Björkbacka H, Pana TA, Demissie S, Ayers C, Elhadad MA, Fornage M, Beiser AS, Benjamin EJ, Boekholdt MS, Engström G, Herder C, Hoogeveen RC, Koenig W, Melander O, Orho-Melander M, Schiopu A, Söderholm M, Wareham N, Ballantyne CM, Peters A, Seshadri S, Myint PK, Nilsson J, de Lemos JA, Dichgans M. Circulating Monocyte Chemoattractant Protein-1 and Risk of Stroke: Meta-Analysis of Population-Based Studies Involving 17 180 Individuals. Circ Res. 2019 Sep 27;125(8):773-782.
Duering M, Finsterwalder S, Baykara E, Tuladhar AM, Gesierich B, Konieczny MJ, Malik R, Franzmeier N, Ewers M, Jouvent E, Biessels GJ, Schmidt R, de Leeuw FE, Pasternak O, Dichgans M. Free water determines diffusion alterations and clinical status in cerebral small vessel disease. Alzheimers Dement. 2018 Jun;14(6):764-774.
Tiedt S, Duering M, Barro C, Kaya AG, Boeck J, Bode FJ, Klein M, Dorn F, Gesierich B, Kellert L, Ertl-Wagner B, Goertler MW, Petzold GC, Kuhle J, Wollenweber FA, Peters N, Dichgans M. Serum neurofilament light: A biomarker of neuroaxonal injury after ischemic stroke. Neurology. 2018 Oct 2;91(14):e1338-e1347.
Malik R, Rannikmäe K, Traylor M, Georgakis MK, Sargurupremraj M, Markus HS, Hopewell JC, Debette S, Sudlow CLM, Dichgans M; MEGASTROKE consortium and the International Stroke Genetics Consortium. Genome-wide meta-analysis identifies 3 novel loci associated with stroke. Ann Neurol. 2018 Dec;84(6):934-939.
Rutten-Jacobs LC, Larsson SC, Malik R, Rannikmäe K; MEGASTROKE consortium; International Stroke Genetics Consortium, Sudlow CL, Dichgans M, Markus HS, Traylor M. Genetic risk, incident stroke, and the benefits of adhering to a healthy lifestyle: cohort study of 306 473 UK Biobank participants. BMJ. 2018 Oct 24;363:k4168.
Malik R, Dau T, Gonik M, Sivakumar A, Deredge DJ, Edeleva EV, Götzfried J, van der Laan SW, Pasterkamp G, Beaufort N, Seixas S, Bevan S, Lincz LF, Holliday EG, Burgess AI, Rannikmäe K, Minnerup J, Kriebel J, Waldenberger M, Müller-Nurasyid M, Lichtner P, Saleheen D; International Stroke Genetics Consortium, Rothwell PM, Levi C, Attia J, Sudlow CL, Braun D, Markus HS, Wintrode PL, Berger K, Jenne DE, Dichgans M. Common coding variant in SERPINA1 increases the risk for large artery stroke. Proc Natl Acad Sci U S A. 2017 Apr 4;114(14):3613-3618.
Tiedt S, Prestel M, Malik R, Schieferdecker N, Duering M, Kautzky V, Stoycheva I, Böck J, Northoff BH, Klein M, Dorn F, Krohn K, Teupser D, Liesz A, Plesnila N, Holdt LM, Dichgans M. RNA-Seq Identifies Circulating miR-125a-5p, miR-125b-5p, and miR-143-3p as Potential Biomarkers for Acute Ischemic Stroke. Circ Res. 2017 Sep 29;121(8):970-980.
Malik R, Traylor M, Pulit SL, Bevan S, Hopewell JC, Holliday EG, Zhao W, Abrantes P, Amouyel P, Attia JR, Battey TW, Berger K, Boncoraglio GB, Chauhan G, Cheng YC, Chen WM, Clarke R, Cotlarciuc I, Debette S, Falcone GJ, Ferro JM, Gamble DM, Ilinca A, Kittner SJ, Kourkoulis CE, Lemmens R, Levi CR, Lichtner P, Lindgren A, Liu J, Meschia JF, Mitchell BD, Oliveira SA, Pera J, Reiner AP, Rothwell PM, Sharma P, Slowik A, Sudlow CL, Tatlisumak T, Thijs V, Vicente AM, Woo D, Seshadri S, Saleheen D, Rosand J, Markus HS, Worrall BB, Dichgans M; ISGC Analysis Group; METASTROKE collaboration; Wellcome Trust Case Control Consortium 2 (WTCCC2); NINDS Stroke Genetics Network (SiGN). Low-frequency and common genetic variation in ischemic stroke: The METASTROKE collaboration. Neurology. 2016 Mar 29;86(13):1217-26. 2016 Sep 20;87(12):1306.
Gormley P, Anttila V, Winsvold BS, Palta P, Esko T, Pers TH, Farh KH, Cuenca-Leon E, Muona M, Furlotte NA, Kurth T, Ingason A, McMahon G, Ligthart L, Terwindt GM, Kallela M, Freilinger TM, Ran C, Gordon SG, Stam AH, Steinberg S, Borck G, Koiranen M, Quaye L, Adams HH, Lehtimäki T, Sarin AP, Wedenoja J, Hinds DA, Buring JE, Schürks M, Ridker PM, Hrafnsdottir MG, Stefansson H, Ring SM, Hottenga JJ, Penninx BW, Färkkilä M, Artto V, Kaunisto M, Vepsäläinen S, Malik R, Heath AC, Madden PA, Martin NG, Montgomery GW, Kurki MI, Kals M, Mägi R, Pärn K, Hämäläinen E, Huang H, Byrnes AE, Franke L, Huang J, Stergiakouli E, Lee PH, Sandor C, Webber C, Cader Z, Muller-Myhsok B, Schreiber S, Meitinger T, Eriksson JG, Salomaa V, Heikkilä K, Loehrer E, Uitterlinden AG, Hofman A, van Duijn CM, Cherkas L, Pedersen LM, Stubhaug A, Nielsen CS, Männikkö M, Mihailov E, Milani L, Göbel H, Esserlind AL, Christensen AF, Hansen TF, Werge T; International Headache Genetics Consortium, Kaprio J, Aromaa AJ, Raitakari O, Ikram MA, Spector T, Järvelin MR, Metspalu A, Kubisch C, Strachan DP, Ferrari MD, Belin AC, Dichgans M, Wessman M, van den Maagdenberg AM, Zwart JA, Boomsma DI, Smith GD, Stefansson K, Eriksson N, Daly MJ, Neale BM, Olesen J, Chasman DI, Nyholt DR, Palotie A. Meta-analysis of 375,000 individuals identifies 38 susceptibility loci for migraine. Nat Genet. 2016 Aug;48(8):856-66.
Baykara E, Gesierich B, Adam R, Tuladhar AM, Biesbroek JM, Koek HL, Ropele S, Jouvent E; Alzheimer's Disease Neuroimaging Initiative, Chabriat H, Ertl-Wagner B, Ewers M, Schmidt R, de Leeuw FE, Biessels GJ, Dichgans M, Duering M. A Novel Imaging Marker for Small Vessel Disease Based on Skeletonization of White Matter Tracts and Diffusion Histograms. Ann Neurol. 2016 Oct;80(4):581-92.
METACOHORTS Consortium. Electronic address: firstname.lastname@example.org; METACOHORTS Consortium. METACOHORTS for the study of vascular disease and its contribution to cognitive decline and neurodegeneration: An initiative of the Joint Programme for Neurodegenerative Disease Research. Alzheimers Dement. 2016 Dec;12(12):1235-1249.
Neurology Working Group of the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium, the Stroke Genetics Network (SiGN), and the International Stroke Genetics Consortium (ISGC). Identification of additional risk loci for stroke and small vessel disease: a meta-analysis of genome-wide association studies. Lancet Neurol. 2016 Jun;15(7):695-707.
Malik R, Freilinger T, Winsvold BS, Anttila V, Vander Heiden J, Traylor M, de Vries B, Holliday EG, Terwindt GM, Sturm J, Bis JC, Hopewell JC, Ferrari MD, Rannikmae K, Wessman M, Kallela M, Kubisch C, Fornage M, Meschia JF, Lehtimäki T, Sudlow C, Clarke R, Chasman DI, Mitchell BD, Maguire J, Kaprio J, Farrall M, Raitakari OT, Kurth T, Ikram MA, Reiner AP, Longstreth WT Jr, Rothwell PM, Strachan DP, Sharma P, Seshadri S, Quaye L, Cherkas L, Schürks M, Rosand J, Ligthart L, Boncoraglio GB, Davey Smith G, van Duijn CM, Stefansson K, Worrall BB, Nyholt DR, Markus HS, van den Maagdenberg AM, Cotsapas C, Zwart JA, Palotie A; International Headache Genetics Consortium, Dichgans M; METASTROKE Collaboration of the International Stroke Genetics Consortium. Shared genetic basis for migraine and ischemic stroke: A genome-wide analysis of common variants. Neurology. 2015 May 26;84(21):2132-45.
Verdura E, Hervé D, Scharrer E, Amador Mdel M, Guyant-Maréchal L, Philippi A, Corlobé A, Bergametti F, Gazal S, Prieto-Morin C, Beaufort N, Le Bail B, Viakhireva I, Dichgans M, Chabriat H, Haffner C, Tournier-Lasserve E. Heterozygous HTRA1 mutations are associated with autosomal dominant cerebral small vessel disease. Brain. 2015 Aug;138(Pt 8):2347-58.
Malik R, Bevan S, Nalls MA, Holliday EG, Devan WJ, Cheng YC, Ibrahim-Verbaas CA, Verhaaren BF, Bis JC, Joon AY, de Stefano AL, Fornage M, Psaty BM, Ikram MA, Launer LJ, van Duijn CM, Sharma P, Mitchell BD, Rosand J, Meschia JF, Levi C, Rothwell PM, Sudlow C, Markus HS, Seshadri S, Dichgans M; Wellcome Trust Case Control Consortium 2. Multilocus genetic risk score associates with ischemic stroke in case-control and prospective cohort studies. Stroke. 2014 Feb;45(2):394-402.
Opherk C, Gonik M, Duering M, Malik R, Jouvent E, Hervé D, Adib-Samii P, Bevan S, Pianese L, Silvestri S, Dotti MT, De Stefano N, Liem M, Boon EM, Pescini F, Pachai C, Bracoud L, Müller-Myhsok B, Meitinger T, Rost N, Pantoni L, Lesnik Oberstein S, Federico A, Ragno M, Markus HS, Tournier-Lasserve E, Rosand J, Chabriat H, Dichgans M. Genome-wide genotyping demonstrates a polygenic risk score associated with white matter hyperintensity volume in CADASIL. Stroke. 2014 Apr;45(4):968-72.
Dichgans M, Malik R, König IR, Rosand J, Clarke R, Gretarsdottir S, Thorleifsson G, Mitchell BD, Assimes TL, Levi C, O'Donnell CJ, Fornage M, Thorsteinsdottir U, Psaty BM, Hengstenberg C, Seshadri S, Erdmann J, Bis JC, Peters A, Boncoraglio GB, März W, Meschia JF, Kathiresan S, Ikram MA, McPherson R, Stefansson K, Sudlow C, Reilly MP, Thompson JR, Sharma P, Hopewell JC, Chambers JC, Watkins H, Rothwell PM, Roberts R, Markus HS, Samani NJ, Farrall M, Schunkert H; METASTROKE Consortium; CARDIoGRAM Consortium; C4D Consortium; International Stroke Genetics Consortium. Shared genetic susceptibility to ischemic stroke and coronary artery disease: a genome-wide analysis of common variants. Stroke. 2014 Jan;45(1):24-36.
Debette S, Kamatani Y, Metso TM, Kloss M, Chauhan G, Engelter ST, Pezzini A, Thijs V, Markus HS, Dichgans M, Wolf C, Dittrich R, Touzé E, Southerland AM, Samson Y, Abboud S, Béjot Y, Caso V, Bersano A, Gschwendtner A, Sessa M, Cole J, Lamy C, Medeiros E, Beretta S, Bonati LH, Grau AJ, Michel P, Majersik JJ, Sharma P, Kalashnikova L, Nazarova M, Dobrynina L, Bartels E, Guillon B, van den Herik EG, Fernandez-Cadenas I, Jood K, Nalls MA, De Leeuw FE, Jern C, Cheng YC, Werner I, Metso AJ, Lichy C, Lyrer PA, Brandt T, Boncoraglio GB, Wichmann HE, Gieger C, Johnson AD, Böttcher T, Castellano M, Arveiler D, Ikram MA, Breteler MM, Padovani A, Meschia JF, Kuhlenbäumer G, Rolfs A, Worrall BB; International Stroke Genetics Consortium, Ringelstein EB, Zelenika D, Tatlisumak T, Lathrop M, Leys D, Amouyel P, Dallongeville J; CADISP Group. Common variation in PHACTR1 is associated with susceptibility to cervical artery dissection. Nat Genet. 2015 Jan;47(1):78-83.
Wardlaw JM, Smith EE, Biessels GJ, Cordonnier C, Fazekas F, Frayne R, Lindley RI, O'Brien JT, Barkhof F, Benavente OR, Black SE, Brayne C, Breteler M, Chabriat H, Decarli C, de Leeuw FE, Doubal F, Duering M, Fox NC, Greenberg S, Hachinski V, Kilimann I, Mok V, Oostenbrugge Rv, Pantoni L, Speck O, Stephan BC, Teipel S, Viswanathan A, Werring D, Chen C, Smith C, van Buchem M, Norrving B, Gorelick PB, Dichgans M; STandards for ReportIng Vascular changes on nEuroimaging (STRIVE v1). Neuroimaging standards for research into small vessel disease and its contribution to ageing and neurodegeneration. Lancet Neurol. 2013 Aug;12(8):822-38.
Duering M, Csanadi E, Gesierich B, Jouvent E, Hervé D, Seiler S, Belaroussi B, Ropele S, Schmidt R, Chabriat H, Dichgans M. Incident lacunes preferentially localize to the edge of white matter hyperintensities: insights into the pathophysiology of cerebral small vessel disease. Brain. 2013 Sep;136(Pt 9):2717-26.
International Stroke Genetics Consortium (ISGC); Wellcome Trust Case Control Consortium 2 (WTCCC2), Bellenguez C, Bevan S, Gschwendtner A, Spencer CC, Burgess AI, Pirinen M, Jackson CA, Traylor M, Strange A, Su Z, Band G, Syme PD, Malik R, Pera J, Norrving B, Lemmens R, Freeman C, Schanz R, James T, Poole D, Murphy L, Segal H, Cortellini L, Cheng YC, Woo D, Nalls MA, Müller-Myhsok B, Meisinger C, Seedorf U, Ross-Adams H, Boonen S, Wloch-Kopec D, Valant V, Slark J, Furie K, Delavaran H, Langford C, Deloukas P, Edkins S, Hunt S, Gray E, Dronov S, Peltonen L, Gretarsdottir S, Thorleifsson G, Thorsteinsdottir U, Stefansson K, Boncoraglio GB, Parati EA, Attia J, Holliday E, Levi C, Franzosi MG, Goel A, Helgadottir A, Blackwell JM, Bramon E, Brown MA, Casas JP, Corvin A, Duncanson A, Jankowski J, Mathew CG, Palmer CN, Plomin R, Rautanen A, Sawcer SJ, Trembath RC, Viswanathan AC, Wood NW, Worrall BB, Kittner SJ, Mitchell BD, Kissela B, Meschia JF, Thijs V, Lindgren A, Macleod MJ, Slowik A, Walters M, Rosand J, Sharma P, Farrall M, Sudlow CL, Rothwell PM, Dichgans M, Donnelly P, Markus HS. Genome-wide association study identifies a variant in HDAC9 associated with large vessel ischemic stroke. Nat Genet. 2012 Feb 5;44(3):328-33.
Freilinger T, Anttila V, de Vries B, Malik R, Kallela M, Terwindt GM, Pozo-Rosich P, Winsvold B, Nyholt DR, van Oosterhout WP, Artto V, Todt U, Hämäläinen E, Fernández-Morales J, Louter MA, Kaunisto MA, Schoenen J, Raitakari O, Lehtimäki T, Vila-Pueyo M, Göbel H, Wichmann E, Sintas C, Uitterlinden AG, Hofman A, Rivadeneira F, Heinze A, Tronvik E, van Duijn CM, Kaprio J, Cormand B, Wessman M, Frants RR, Meitinger T, Müller-Myhsok B, Zwart JA, Färkkilä M, Macaya A, Ferrari MD, Kubisch C, Palotie A, Dichgans M, van den Maagdenberg AM; International Headache Genetics Consortium. Genome-wide association analysis identifies susceptibility loci for migraine without aura. Nat Genet. 2012 Jun 10;44(7):777-82.
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.
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.
Maria Kaffe, clinician scientist
Barbara Lindner, technical assistant
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.
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.
Karin Waegemann, research coordinator
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.
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.
Federica Tosato, PhD student
Jule Filler, PhD student
Arailym Aronova, PhD student
Luise Schröger, PhD student
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.
Matthias Prestel, PostDoc
Christof Haffner, PostDoc
We gratefully acknowledge support for our work by the following funding agencies:
Fondation Leducq: Leducq Trans-Atlantic Network of Excellence On Brain Endothelium: A Nexus for Cerebral Small Vessel Disease, Coordinator: Martin Dichgans
Jan 2023 – Dec 2027
Genetics of Early-Onset Stroke Consortium (NIH-subaward)
Jan 2018 – Dec 2022
Small vessel diseases in a mechanistic perspective: Targets for Intervention – Affected pathways and mechanistic exploitation / Martin Dichgans
Jan 2016 - Dec 2021
Munich Cluster for Systems Neurology (SyNergy I+ II) (DFG)
Nov 2012 – Juni 2022
Aufdeckung der Rolle von seltenen und low-frequency Mutationen bei Schlaganfall mittels eines „polygenic risk score“ – informierten Sequenzieransatzes – Implikationen für die Risikoprädiktion / Martin Dichgans, Rainer Malik
Mai 2022 – April 2025
Project B3: Martin Dichgans/Yaw Asare – Mechanistic role of HDAC9 in atherosclerosis (Role of HDAC9 in Atherosclerosis – Project within the collaborative research programme SFB 1123 ‘Atherosclerosis)
Jul 2018 – Jun 2022
Forschergruppe „ImmunoStroke: Von der Immunzelle zur Schlagabfallregeneration“ (DFG) Teilprojekt C2 „Mikroglia-PET als Surogatmarker für Neuroinflammation nach Schlaganfall“ Martin Dichgans
Juli 2019 – Juni 2022
CLINSPECT-M, CLINICAL MASS SPECTROMETRY CENTER MUNICH; Teilprojekt B: Neurovascular Diseases / Martin Dichgans
Mar 2020 – Feb 2023
DEMDAS – DZNE Mechanisms of Dementia after Stroke / Martin Dichgans
Jan 2013 - Dec 2023
DigiMed – P4 Medizin von Carotis Stenose und Schlaganfall (Bayerisches Staatsministerium für Gesundheit und Pflege)
Oct 2018 – Nov 2024
The Advanced Clinician Scientist Program for Comprehensive Neuroscience (PROMISE)
April 2021 - Mar 2022
Vascular Dementia Research Foundation: The Institute for Stroke and Dementia Research
Martin Dichgans | CV
Martin Dichgans, MD
Professor, Ludwig-Maximilians University (LMU), Munich
Chair, Stroke and Dementia Research
Since 2010 Founding Director, Institute for Stroke and Dementia Research, LMU Hospital, Ludwig-Maximilians University (LMU), Munich Germany
Since 2010 Chair Dept. of Translational Stroke and Dementia Research
Since 2009 Managing Director, Interdisciplinary Stroke Center Munich, LMU Hospital, Munich German
Since 2006 Professor of Neurology, Ludwig-Maximilians University (LMU), Munich
Since 2001 Board Certificate in Neurology, Ludwig-Maximilians University (LMU), Munich
Until 1993 Study of Medicine at the University of Heidelberg, Ludwig-Maximilians University (LMU), and Ann Arbor, Michigan (USA)
Since 2020 President, European Stroke Organisation (ESO)
Since 2016 President, German Stroke Society (DSG) and Board of Directors (since 2014)
Since 2015 Executive Committee, European Stroke Organization (ESO)
Since 2014 Chair, Scientific Advisory Board, ERANET-NEURON, FP7 European Union
Since 2012 Scientific Board and Research Coordinator, Munich Cluster of Systems Neurology (SyNergy)
Since 2011 Coordinator, Clinical Research DZNE, Munich
Editor Roles and Editorial Boards
Since 2017 Annals of Neurology, Editorial Board
Since 2016 European Stroke Journal (ESO), Editorial Board
Since 2015 Stroke (AHA), Section Editor
Since 2013 Int J Stroke (WSO), Section Editor
Since 2010 Frontiers in Stroke, Associate Editor
2011 – 2016 J Neurochemistry, Handling Editor
2010 – 2015 Stroke (AHA), Assistant Editor
2006 – 2010 Stroke (AHA), Section Editor
Fields of Interest
Stroke with a special focus on Genetics
Small Vessel Disease
Dichgans Lab at ISD Research Retreat
ESO Conference in Munich
May 2023 – The European Stroke Organisation Conference ESOC 2023 opened with a public awareness campaign and proceeded with an extensive scientific programme including the presentation of large international trials in plenaries, workshops, teaching courses and other formats. ISD researchers served as the local hosts and also presented results >>