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                                                  Marios Georgakis – Epidemiology and Bioinformatics

                                                  • Research focus
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                                                  Cerebrovascular diseases, such as ischemic stroke, cerebral small vessel disease, intracerebral hemorrhage, and vascular dementia represent a leading cause of death and and disability worldwide. Our work is motivated by a pressing need to improve cerebrovascular health in the general population with the development of precise and personalized preventive and therapeutic strategies. To this end, we use large-scale and multi-dimensional data from epidemiological studies and human biobanks (genomics, transcriptomics, proteomics, clinical data, and imaging) and apply innovative bioinformatic tools to inform such strategies. 

                                                  Our goals include: (i) the discovery and dissection of causal mechanisms contributing to cerebrovascular disease, (ii) the exploration of these mechanisms as potential targets for therapeutic and preventive strategies, and (iii) the development of personalized risk stratification tools for patients with or at risk for cerebrovascular disease. 

                                                  Epidemiology and Bioinformatics Focus 

                                                  Discovery of causal mechanisms contributing to cerebrovascular disease

                                                  Using human genetic data as our starting point, we bridge different multiomics levels with causal inference methods, such as Mendelian randomization, in order to dissect mechanisms leading to cerebrovascular disease. A key focus of the lab is the dissection of immune mechanisms underlying atherosclerosis, one of the main causes of stroke and cardiovascular disease in general. For this purpose, we have recently developed the AtherOMICS biobank, which involves the collection of atherosclerotic plaque samples from patients undergoing endarterectomy. Another emerging area of interest includes the mechanisms connecting established vascular risk factors, such as blood pressure, diabetes, and obesity, with cerebral small vessel disease.

                                                  Following-up signals with translational potential to inform the design of clinical trials

                                                  Pharmaceutical agents targeting mechanisms with genetic evidence for involvement in human disease are more likely to reach approval for use. As such, of the targets with a high translational potential, as supported by our genomic analyses. We triangulate evidence from human genetics with data from epidemiological studies, human biobanks, and experimental models. Furthermore, in collaboration with other labs at the ISD or externally, we aim to follow-up our signals with translational work involving either animal models or diagnostic studies in humans, with the aim of providing design roadmaps for future clinical trials. We recently successfully applied this model to the CCL2/CCR2 pathway, providing compelling evidence for its translational potential as a target of atheroprotective treatments.

                                                  Development of personalized biomarkers and risk stratification tools

                                                  Cerebrovascular disease is highly heterogeneous, as is the predisposition of individuals to it depending on their genetic profiles and lifestyles. Over and over again, we continue seeing that the one-size fits all approaches we apply in the clinic do not equally work for all. As such, the third key area of exploration involves the development of more efficient tools for risk stratification that will allow more personalized treatments. The approaches we apply range from the development of polygenic risk scores in the general population to deploying deep learning methods in neuroimaging studies of stroke patients. Our vision is to identify individuals that might benefit from specific preventive or therapeutic approaches. 

                                                  Contact:

                                                  Dr. Marios Georgakis

                                                  E-Mail: marios.georgakis@med.uni-muenchen.de

                                                  Key Publications

                                                  > All Publications

                                                  2022

                                                  Georgakis MK, Bernhagen J, Heitman L, Weber C, Dichgans M. Targeting the CCL2-CCR2 Axis for Atheroprotection: Triangulation of Evidence and Steps Towards Clinical Translation. Eur Heart J. 2022 May 14;43(19):1799-1808.

                                                  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, …, Debette S. Stroke genetics informs drug discovery and risk prediction across ancestries. Nature. 2022 Sep 30;1-15.

                                                  Mayerhofer E, Malik R, Parodi L, Burgess S, Harloff A, Dichgans M, Rosand J, Anderson CD, Georgakis MK. Genetically predicted on-statin LDL response is associated with higher intracerebral haemorrhage risk. Brain. 2022 Aug 27;145(8):2677-2686.

                                                  De Marchis GM, Dittrich TD, Malik R , Zietz AV , Kriemler LF, Ference BA , Dichgans M , Georgakis MK. Genetic proxies for PCSK9 inhibition associate with lipoprotein(a): Effects on coronary artery disease and ischemic stroke. Atherosclerosis. 2022 Sep 26;S0021-9150(22)01433-2.

                                                  Georgakis MK, Malik R, Richardson TG, Howson JMM, Anderson CD, Burgess S, Hovingh GK, Dichgans M, Gill D. Associations of genetically predicted IL-6 signaling with cardiovascular disease risk across population subgroups. BMC Med. 2022 Aug 11;20(1):245. 

                                                  Georgakis MK, Parodi L, Frerich S, …, Anderson CD. Genetic architecture of stroke of undetermined source: overlap with known stroke etiologies and associations with modifiable risk factors. Ann Neurol. 2022 May;91(5):640-651.

                                                  Georgakis MK, Rong F, Düring M, …, Dichgans M. Cerebral small vessel disease burden and cognitive and functional outcomes after stroke: A multicenter prospective cohort study. Alzheimers Dement. 2022 Jul 25. Online ahead of print

                                                  Živković L, Asare Y, Bernhagen J, Dichgans M, Georgakis MK. Pharmacological Targeting of the CCL2/CCR2 Axis for Atheroprotection: A Meta-Analysis of Preclinical Studies. Arterioscler Thromb Vasc Biol. 2022 May;42(5):e131-e144.

                                                  Papadopoulos A, Palaiopanos K, Björkbacka H, …, Georgakis MK. Circulating interleukin-6 levels and incident ischemic stroke: a systematic review and meta-analysis of prospective studies. Neurology. 2022 Mar 8;98(10):e1002-e1012.

                                                  Georgakis MK, Malik R, Burgess S, Dichgans M. Additive Effects of Genetic Interleukin-6 Signaling Downregulation and Low-Density-Lipoprotein Cholesterol Lowering on Cardiovascular Risk: A 2X2 Factorial Mendelian Randomization Analysis. J Am Hear Assoc. 2022 Jan 4;11(1):e023277.

                                                  2021

                                                  Georgakis MK, van der Laan S., Asare Y., ..., Dichgans M. Monocyte-chemoattractant protein-1 Levels in Human Atherosclerosis Associate with Plaque Vulnerability. Arterioscler Thromb Vasc Biol. 2021;41(6):2038-2048.

                                                  Georgakis MK, Gill D. Mendelian Randomization Studies in Stroke: Exploration of Risk Factors and Drug Targets With Human Genetic Data. Stroke. 2021. Aug;52(9):2992-3003.

                                                  Georgakis MK, de Lemos JA, Ayers C, …, Dichgans M. Circulating monocyte chemoattractant protein-1 levels are associated with cardiovascular mortality: a meta-analysis of population-based studies. JAMA Cardiol. 2021;6(5):587-592.

                                                  Georgakis MK, Malik R, Li X, …, Dichgans M. Genetically downregulated interleukin-6 signaling is associated with a favorable cardiometabolic profile: a phenome-wide association study. Circulation. 2021;143(11):1177-1180.

                                                  Malik R*, Georgakis MK*, Neitzel J, …, Dichgans M. Midlife vascular risk factors and risk of incident dementia: longitudinal cohort and Mendelian randomization analyses in the UK Biobank. (*equally contributed). Alzheimers Dement. 2021;17(9):1422-1431.

                                                  Malik R, Georgakis MK, Vujkovic M, Damrauer SM, Burgess S, Dichgans M, Gill D. Relationship between blood pressure and incident cardiovascular disease: linear and non-linear Mendelian randomization analyses. Hypertension. 2021;77(6):2004-2013.

                                                  Georgakis MK, Harshfield E, Malik R, …, Dichgans M. Diabetes mellitus, glycemic traits, and cerebrovascular disease: a Mendelian randomization study. Neurology. 2021;96(13):e1732-e1742.

                                                  2020

                                                  Georgakis MK, Malik R, Gill D, …, Dichgans M. Interleukin-6 signaling effects on ischemic stroke and other cardiovascular outcomes: a Mendelian Randomization study. Circ Genom Precis Med. 2020;13(3):e002872.

                                                  Georgakis MK, Malik R, Anderson CD, Parhofer KG, Hopewell JC, Dichgans M. Genetically determined blood lipids and cerebral small vessel disease: role of HDL cholesterol. Brain. 2020;143(2):597-610.

                                                  Papadopoulos A, Palaiopanos K, Protogerou AP, Paraskeuas G, Tsivgoulis G, Georgakis MK. Left ventricular hypertrophy and cerebral small vessel disease: a systematic review and meta-analysis. J Stroke. 2020;22(2):206-224.

                                                  Georgakis MK, Gill D, Malik R, Protogerou AD, Webb WJS,…, Dichgans M. Genetically predicted blood pressure across the lifespan: differential effects of mean and pulse pressure on stroke risk. (*equally contributed). Hypertension. 2020 Sep;76(3):953-961.

                                                  Georgakis MK, Gill D, Webb AJS, Evangelou E, Elliott P, Sudlow CLM, Dehghan A, Malik R, Tzoulaki I, Dichgans M. Genetically determined blood pressure, antihypertensive drug classes, and risk of stroke: a Mendelian Randomization Study. Neurology. 2020 Jul 28;95(4):e353-e361.

                                                  Marini S*, Georgakis MK*, …, Andreson CD. Genetic overlap and causal inferences between impaired kidney function and cerebrovascular diseases. Neurology. 2020;94(24):e2581-e2591. (*equally contributed).

                                                  2019

                                                  Georgakis MK, Malik R, Björkbacka H, …, Dichgans M. Circulating monocyte chemoattractant protein-1 and risk of stroke: a meta-analysis of population-based studies involving 17,180 individuals. Circ Res 2019;125(8):773-782. 

                                                  Georgakis MK, Gill D, Rannikmäe K, …, Dichgans M. Genetically Determined Levels of Circulating Cytokines and Risk of Stroke: Role of Monocyte Chemoattractant Protein-1. Circulation 2019;139(2):256-268. 

                                                  Gill D*, Georgakis MK*, Koskeridis F, …, Dichgans M*, Tzoulaki I*. Use of Genetic variants related to antihypertensive targets to inform on efficacy and side effects. Circulation. 2019;140(4):270-279. (*equally contributed)

                                                  Georgakis MK, Duering M, Wardlaw JM, Dichgans M. WMH and long-term outcomes in ischemic stroke: a systematic review and meta-analysis. Neurology. 2019;92(12):e1298-e1308. 

                                                  Georgakis MK, Beskou-Kontou T, Theodoridis I, Skalkidou A, Petridou ET. Surgical menopause in association with cognitive function and risk of dementia: A systematic review and meta-analysis. Psychoneuroendocrinology. 2019 Aug; 106:9-19.

                                                  2018

                                                  Zietemann V*, Georgakis MK*, Dondaine T, Müller C, Mendyk AM, Kopczak A, Hénon H, Bombois S, Wollenweber FA, Bordet R, Dichgans M. Early MoCA predicts long-term cognitive and functional outcome and mortality after stroke. Neurology. 2018;91(20):e1838-e1850. (*equally contributed)

                                                  Georgakis MK, Chatzopoulou D, Tsivgoulis G, Petridou ET. Albuminuria and Cerebral Small Vessel Disease: A Systematic Review and Meta-Analysis. J Am Geriatr Soc. 2018;66(3):509-517.

                                                  2017

                                                  Georgakis MK, Dimitriou NG, Karalexi MA, …, Petridou ET. Albuminuria in association with dementia and cognitive function: a systematic review and meta-analysis. J Am Ger Soc. 2017;65(6):1190-1198. 

                                                  Georgakis MK, Synetos A, Mihas C, Karalexi MA, Tousoulis D, Seshadri S, Petridou ET. Left ventricular hypertrophy in association with cognitive impairment: a systematic review and meta-analysis. Hypertens Res. 2017 Jul;40(7):696-709. 

                                                  2016

                                                  Georgakis MK, Kalogirou EI, Diamantaras AA, Daskalopoulou SS, Munro CA, Lyketsos CG, Skalkidou A, Petridou ET. Age at menopause and duration of reproductive period in association with dementia and cognitive function: A systematic review and meta-analysis. Psychoneuroendocrinology. 2016 Nov;73:224-243.

                                                  Georgakis MK, Thomopoulos TP, Diamantaras AA, Kalogirou EI, Skalkidou A, Daskalopoulou SS, Petridou ET. Age at menopause and duration of reproductive period in association with depression in postmenopausal women: a systematic review and meta-analysis. JAMA Psychiatry. 2016;73(2):139-149.

                                                  Marios Georgakis / PI

                                                  Marek Konieczny / MD Student

                                                  Jana Mattar / MD Student

                                                  Murad Omarov / MSc

                                                  Anushree Ray / MSc

                                                  Andreas Papadopoulos / MD

                                                  Stefan Mayrhofer / MD Student

                                                  Luka Zivkovic / MD student

                                                  Marios Georgakis, Principal investigator

                                                  I am a clinician-scientist interested in stroke care and research. My overarching goal is to identify causal risk factors of cerebrovascular disease in order to inform preventive strategies for lowering the burden of stroke in the community. I believe that human genetics can offer key insights into disease pathophysiology, as evidenced by the comparatively high success rates of drugs with genetic support for their targets. As such, starting from large-scale genomic data, in my lab, we apply bioinformatic and high-throughput experimental analyses across multiple omics levels to discover causal mechanisms for cerebrovascular disease and inform the design of trials targeting.

                                                  Personal data:

                                                  Marios Georgakis, MD, PhD

                                                  Date of birth: October 31, 1991

                                                  Place of birth: Lefkada, Greece

                                                  Education

                                                  2019-today: Clinical Residency in Neurology, LMU University Hospital, Munich, Germany

                                                  2017-2020: Doctoral studies (Ph.D.) in Graduate School of Systemic Neurosciences (GSN), LMU Munich, Germany

                                                  2015-2019: Doctoral studies (D.Sc.) in Epidemiology, National and Kapodistrian University of Athens, Greece

                                                  2015-2017: Master studies (M.Sc.): Molecular Physiology (Neurosciences), National and Kapodistrian University of Athens, Greece

                                                  2009-2015: Medical studies (M.D.): Medical School, National and Kapodistrian University of Athens, Greece

                                                  Positions and employment:

                                                  2022-: Junior Group Leader, Institute for Stroke and Dementia Research, LMU Munich

                                                  2022-: Visiting scientist, Broad Institute of MIT and Harvard, Cambridge, MA, USA

                                                  2021-2022: Postdoctoral research fellow, Center for Genomic Medicine, Massachusetts General Hospital & Broad Institute of MIT and Harvard, Boston, MA, USA

                                                  2020-2021: Postdoctoral researcher (clinician-scientist), Institute for Stroke and Dementia Research & Neurology Department, LMU University Hospital Munich

                                                  2020-: Neurology resident physician, Institute for Stroke and Dementia Research and Department of Neurology, LMU University Hospital, Munich

                                                  2017-2020: Doctoral researcher, Institute for Stroke and Dementia, University Hospital, LMU Munich

                                                  2015-2019: Doctoral researcher, Department of Epidemiology, Medical School, University of Athens

                                                  2016-2017: Master thesis student, Lab of Neurodegenerative diseases, Bio-academy of Athens (BRFFA)

                                                  2015-2017: Research assistant, Department of Women’s Health, Uppsala University

                                                  2013-2015: Undergraduate research fellow, Department of Epidemiology, Medical School, University of Athens

                                                  Honors:

                                                  2021: CHARGE¨ Meritorious Abstract Award

                                                  2021-2022: Walter-Benjamin Fellowship for postdoctoral research by German Research Foundation (DFG)

                                                  2019: Best Oral Presentation at Meeting of International Stroke Genetics Consortium, St. Louis, US

                                                  2019: Best Poster award at European Stroke Organization Conference (ESOC 2019), Milan, Italy

                                                  2018-today: Scholarship for Doctoral studies by the Onassis Foundation

                                                  2018-2019: Research Grant for Doctoral studies by the German Academic Exchange Service (DAAD)

                                                  2015-2017: Scholarship for Master studies by the Bodossaki Foundation

                                                  2010-2015: Scholarship for Medical studies by the Antonios Papadakis legacy

                                                  2008: Third Award by Greek Mathematical Society in national “Euclid” exams 

                                                  Funding:

                                                  We gratefully acknowledge funding by the following funding organizations:

                                                  Developing personalized biomarkers of subclinical arterial pathology with deep learning in carotid ultrasound images

                                                  2022 – 2025

                                                  SyNergy - Munich Cluster for Systems Neurology

                                                  Deconvoluting the immune landscape of carotid atherosclerosis 

                                                  2022 – 2025

                                                  DFG Deutsche Forschungsgemeinschaft

                                                  Elucidating the etiology of cryptogenic stroke with human genetics 

                                                  2021 – 2022

                                                  FöFoLe

                                                  Circulating MCP-1 levels and risk of recurrent cardiovascular events

                                                  2021 – 2022

                                                  Deutscher Akademischer Austauschdienst

                                                  Circulating levels of inflammatory cytokines and risk of stroke and its subtypes

                                                  2018 – 2020

                                                  Follow us on Twitter: @mgeorgakis1

                                                  Contact

                                                  Institute for Stroke and Dementia Research (ISD)
                                                  University Hospital, LMU Munich

                                                  Director: Prof. Dr. med. Martin Dichgans

                                                  Feodor-Lynen-Straße 17
                                                  81377 Munich, Germany

                                                  Phone: +49 (0)89 4400 46019
                                                  www.isd-research.de
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                                                  DZNE – Deutsches Zentrum für Neurodegenerative Erkrankungen

                                                  SyNergy – Munich Cluster for Systems Neurology

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