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.
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.
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.
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.
Marios Georgakis, MD, PhD
Date of birth: October 31, 1991
Place of birth: Lefkada, Greece
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
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
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
Deconvoluting the immune landscape of carotid atherosclerosis
2022 – 2025
Elucidating the etiology of cryptogenic stroke with human genetics
2021 – 2022
Circulating MCP-1 levels and risk of recurrent cardiovascular events
2021 – 2022
Circulating levels of inflammatory cytokines and risk of stroke and its subtypes
2018 – 2020