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                                                    3. Georgakis Lab

                                                    Marios Georgakis 
                                                    Epidemiology and Bioinformatics – Stroke Precision Lab

                                                    • Research focus
                                                    • Publications
                                                    • Team
                                                    • The PI
                                                    • Funding

                                                    Cerebrovascular disease represents a leading cause of death and disability worldwide. Despite major progress in understanding the highly heterogeneous etiology of cerebrovascular disease in recent decades, our preventive approaches remain at large not pathology-oriented. Our work is motivated by a pressing need to optimize cerebrovascular health with the development of precise and personalized preventive strategies. We use large-scale and multi-dimensional data from epidemiological studies and human biobanks (genomics, transcriptomics, proteomics, imaging) and apply bioinformatic tools to inform such strategies. We have a special focus on extra- and intracranial atherosclerosis, one of the most common causes of cerebrovascular disease.

                                                    Our goals include: (i) the discovery of disease-modifying drug targets for novel therapeutic and preventive strategies against cerebrovascular disease, (ii) the deeper molecular and cellular phenotyping of cerebrovascular pathologies, (iii) the discovery of in vivo biomarkers of cerebrovascular disease activity, and (iv) the development of personalized risk stratification tools for patients with or at risk for cerebrovascular disease.

                                                    Discovery of drug targets for 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. Our vision is to inform the development of disease-modifying treatments for cerebrovascular pathologies by triangulating the results from human genetics with data from epidemiological studies, human biobanks, and experimental models.

                                                    Deeper molecular phenotyping of cerebrovascular disease

                                                    Using human samples, we apply novel high-throughput techniques, such as single-cell sequencing and spatial transcriptomics to deeper characterize cerebrovascular disease lesions at higher resolution. For this purpose, we recently developed the AtherOMICS biobank, which involves the collection of atherosclerotic plaque samples from patients undergoing carotid endarterectomy. Our vision is to detect disease processing signatures with diagnostic and therapeutic relevance.

                                                    Discovery of in vivo personalized biomarkers

                                                    The third key area of exploration involves the discovery of novel readouts of cerebrovascular disease presence and activity. We bridge data from high-throughput molecular technologies in human samples with imaging technologies, such as CT and MRI, as well as with multiomics analyses of peripheral blood samples, in order to detect in vivo phenotypes of disease activity. Our vision is to use such in vivo biomarkers as endpoints in clinical trials testing disease-modifying treatments. 

                                                    Development of 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 see that the one-size fits all approaches we apply in the clinic do not equally work for all. We aim to develop efficient risk stratification tools by applying approaches that 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

                                                    2023

                                                    Myserlis EP, Anderson CD, Georgakis MK. Genetically Proxied CRP (C-Reactive Protein) Levels and Lobar Intracerebral Hemorrhage Risk. Stroke. 2023 Apr;54(4):e130-e132. doi: 10.1161/STROKEAHA.122.041889. Epub 2023 Mar 9. 

                                                    Myserlis EP, Georgakis MK, Demel SL, Sekar P, Chung J, Malik R, Hyacinth HI, Comeau ME, Falcone GJ, Langefeld CD, Rosand J, Woo D, Anderson CD. A Genomic Risk Score Identifies Individuals at High Risk for Intracerebral Hemorrhage. Stroke. 2023 Apr;54(4):973-982. doi: 10.1161/STROKEAHA.122.041701. Epub 2023 Feb 17. 

                                                    Mayerhofer E, Parodi L, Prapiadou S, Malik R, Rosand J, Georgakis MK, Anderson CD. Genetic Risk Score Improves Risk Stratification for Anticoagulation-Related Intracerebral Hemorrhage. Stroke. 2023 Mar;54(3):791-799. doi: 10.1161/STROKEAHA.122.041764. Epub 2023 Feb 9. 

                                                    Georgakis MK, Anderson CD. Polygenic Risk Scores in the Clinic: A Case for Stroke Survivors. Neurology. 2023 Jan 23:10.1212/WNL.0000000000206899. doi: 10.1212/WNL.0000000000206899. Epub ahead of print. 

                                                    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 / PhD student

                                                    Anushree Ray / PhD student

                                                    Andreas Papadopoulos / PhD student

                                                    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:

                                                    Dissecting the causes of cerebrovascular atherosclerosis with population genetics 

                                                    2023 – 2026

                                                    Multi-omics characterization of the immune mechanisms driving human atheroprogression

                                                    2023 – 2029

                                                    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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