Comprehensive gene-mapping study of extreme MRI-defined cerebral small vessel disease reveals TRIM47 as a strong candidate

Jean-Sebastien Liegey

Vascular Neurologist and SHIVA research physician

His clinical activity is carried out at the Bordeaux University Hospital between the neurovascular unit, the cardiovascular diseases department and the neurodegenerative diseases institute.

He is a awardee of a hospital-based clinical research program (PHRC-I ECOPSEM) in collaboration with the Institute of Cognitive and Integrative Neurosciences of Aquitaine (UMR5287) on mood disorders after stroke, and author of publications related to stroke management, vascular mood disorders and systemic inflammation.

He holds a European Master's degree in Neuroscience with a focus on structural alterations in cerebro-cerebellar networks in the stroke model and their relationship to mood disorders and inter-university diplomas in neurovascular pathology and inflammatory pathology of the central nervous system.


Xavier Levecq

Chief Technical Officer, Imagine Eyes

Xavier Levecq contributes boundless creativity in the development of Imagine Eyes’ products. Before the inception of Imagine Eyes, he also cofounded Imagine Optic together with Samuel Bucourt and designed new wavefront sensors devices - now recognized worldwide as the reference for optical metrology - that propelled their venture into an international success.

Earlier, recruited by CILAS-EADS while still at university, Xavier developed high-tech optronic systems for « StarWars » military applications based on advanced space optics technologies. Now author of more than 30 patents, Xavier graduated from the Institut d’Optique Graduate School in 1993.



Chief Executive Officer, Imagine Eyes

Nicolas Chateau, PhD, has built his career on bringing innovative ophthalmic products to market. He has driven Imagine Eyes to commercialize the rtx1 retinal camera, a breakthrough imaging device that allows doctors to examine the back of the eye with cellular resolution.

Since he cofounded the company in 2003, Nicolas has established strong partnerships with leading academic and clinical centers, and secured several millions Euros in governmental and European funding. Previously, he worked at developing new high-tech optical products for major companies including Coherent, Ocular Sciences and Essilor.

Author of 12 patents and dozens of scientific publications, Nicolas received his PhD in physics from the University of Paris in 1993 after graduating from the Institut d’Optique Graduate School in 1988.


Fabrice Crivello

Research Director, UMR 5293 Center

Fabrice Crivello is research director at the CEA. His works are at the interface between methodology in neuroimaging and research in cognitive neuroimaging and neuroepidemiology. 

Following university studies in signal and image processing, he joined the GIN in 1993. Within the SHFJ in Orsay, he obtained a PhD in biological and medical engineering on the detection of cerebral activations with PET. At the Cyceron center in Caen, he completed a post-doctoral internship aiming at building a multi-scale and multi-modality cerebral imaging database. In 1998, he was recruited as a research officer at the CEA and obtained his authorization to conduct research in March 2006. Since 2011 he has been assigned to Bordeaux, where, he and the GIN, have joined the IMN in 2016.

His research is structured along two complementary axes. The first concerns the development, implementation and distribution of automated procedures dedicated to the extraction of structural cerebral phenotypes. The second one concerns the study of these phenotypes in the context of the exploitation of large cerebral imaging cohorts in order to :

  • characterize cerebral anatomical asymmetries, their factors of variability and their genetic determinant;
  • map the maturation and aging of cerebral anatomy.



SHIVA Co-coordinator, WP3 Leader, Cardiologist

Thierry Couffinhal is Professor of Cardiology and head of the clinical unit of the CEPTA, «Exploration, Prevention and Care Center for Atherosclerosis ». This Unit is dedicated to exploration, prevention and long-term treatment and management of atherosclerotic diseases (angina and myocardial infarction, stroke, peripheral arterial disease) and primary prevention in high-risk patients. Explorations are based on non-invasive up-to-date echographic and other vascular tools. Management is based on a multidisciplinary approach integrating large therapeutic education programs.

Thierry Couffinhal currently participates in many industrial or academic clinical research programs. has been at the head of an Inserm Unit (French Institute of Health and Medical Research) since 2007. The laboratory explores the role of major signaling pathways (Wnt / Hedgehog / JAK2) in vascular biology and thrombosis during development and diseases.

In the last 5 years, he obtained grants from the Fondation Recherche Médicale (FRM), the Agence Nationale de la Recherche (ANR), the Fédération Française de Cardiologie, the health ministry (Programme hospitalier de recherche clinique - PHRC), the Aquitaine Region. He is a member of Société Française de Cardiologie, Société Française d’Angiogenèse and has served on the Scientific Council of the University of Bordeaux (2007-2013). He is also a partner in the European consortium EVGN “European Vascular Genomic Network”, FP6 (2005-2010).

S. Debette

Stéphanie DEBETTE

SHIVA Coordinator, WP6 Leader, Researcher and Neurologist

Stéphanie Debette is a PUPH in epidemiology/public health at the University of Bordeaux (INSERM U1219, Bordeaux Population Health research center) where she co-lead a genetic and integrative epidemiology team on neurological and vascular diseases, and a neurologist at Bordeaux University Hospital. Her research focuses on the genetic and environmental determinants of stroke, MRI markers of brain aging, small vessel disease, and cognition.

Since 2004, she has initiated and coordinated the international CADISP consortium on genetic and environmental risk factors for cervical artery dissection and stroke in young subjects. She chaired the International Stroke Genetics consortium between 2017 and 2019, is a member of the scientific committee of the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium, and sits on the board of directors of the World Stroke Organization. She is co-author of 200 papers, including first or last author in Nat Genet, Lancet Neurol, BMJ. She has been awarded an ERC Starting Grant for the SEGWAY project and coordinates the JPND-BRIDGET project on (epi-)genetic determinants of MRI markers of brain aging.

Since the end of 2019, she is the coordinator of the RHU SHIVA project "Stopping cognitive decline and dementia by fighting covert cerebral small vessel disease". She is also a partner in the H2020 PRESTIGE-AF project on the prevention of ischemic stroke in patients with atrial fibrillation. In 2016 she was awarded with the Fondation Claude Pompidou prize for her research on Alzheimer's disease and in 2019 with the European Stroke Organization's prize for scientific excellence in stroke research. Since 2015, she has initiated and co-organised the Neurepiomics summer school on neuroepidemiology in the age of high-speed technologies, in collaboration with Boston University and Kyoto University. A former Fulbright and Bettencourt-Schueller fellow at the Framingham Heart Study, she was also an adjunct associate professor at Boston University and a visiting professor at the Center for Genomic Medicine at Kyoto University.

She was also Vice-President in charge of external relations at the University of Bordeaux (2018-22) and was the inaugural chair of the ENLIGHT European University Alliance board of directors (2019-22).

She is currently the Director of the Bordeaux Population Health research center (University of Bordeaux – Inserm U1219) and a member of the University Council of the LMU University in Munich (2019-22).

R. Thiebaut


Deputy Director of BPH Center UMR1219

Rodolphe Thiebaut is a medical doctor, with specialization in Public Health. He holds a PhD in Biostatistics from Bordeaux University.

He started his research carrier at the Institut National de Sante et de la Recherche Medicale (INSERM) as a research scientist between 2002 and 2009 and as research director between 2010 and 2013. He has been a research fellow in the Immunobiology Division of the Institute of Child Health (London, UK) in 2007.

He is now Professor in Public Health / Biostatistics at the University of Bordeaux. He leads a research group (SISTM - Statistics in Systems Biology and Translational Medicine) devoted to the modelling and analysis of high-dimensional data mainly applied to immunology through the French Vaccine Research Institute ( This group, which is embedded in the INSERM U1219 Research Centre (, has been recognized as an INRIA project team since January 2015 ( Its translational research starts with immunological questions and ends with the development of statistical methods for the collection and analysis of high-dimensional datasets generated in this domain.

He is in charge of the medical information department of the Bordeaux University Hospital. He is also the Director of the Department of research in Public Health of the Bordeaux University, the deputy director of the INSERM U1219 Research Centre (11 research teams) and the Director of the Graduate School of Digital Public Health, coordinator of the Master of Public Health Data Science at ISPED (Institut de Santé Publique d’Epidémiologie et de Dévelopement). He is the author/co-author of more than 300 publications in peer-reviewed journals including the New England Journal of Medicine, Lancet, AIDS, Journal of Immunology, Biometrics, Biostatistics, Statistics in Medicine, Plos Computational Biology.

P. Boutinaud


Biomedical Chief Technical Officer, Fealinx

Philippe Boutinaud is currently Technical and Innovation Director of the Fealinx Group (turnover: €11M, 70 employees). He obtained his PhD in Computer Science in 1993 at the University of Paris Sud and then began an industrial career in the world of PLM (Product Lifecycle Management) and digital simulation at SDRC (Structural Dynamic Research Corporation) as an R&D engineer and then head of a software development team. In 1999, he took part in the creation of the Cadesis company, which became Fealinx.

His field of technical and scientific expertise includes governance, specification and software engineering on development projects in the fields of PLM, KM (Knowledge Management), CAD (Computer Aided Design), digital simulation and finally data management and machine learning in biomedical imaging. He was the industrial leader of four CIFRE theses carried out at Fealinx, was the coordinator of the ANR ISemantec project (ANR-06-TLOG-0018), coordinator of the ANR BIOMIST project (ANR-13-CORD-0007) and is the co-director of the LABCOM Ginesislab (ANR 16-LCV2-0006-01).

M. Pâques


Ophtalmologist, 15-20 ophthalmology hospital

Michel Paques is an ophthalmologist and manages a multidisciplinar high-resolution imaging platform for the eye at the Quinze-Vingts hospital ( With his team of physicists, computer scientists and biologists, he has developed innovative technologies in particular to observe vessels both in terms of their morphology and blood flow.

M. Joliot


Research Director, UMR 5293 Center

Marc Joliot, Ph.D. is a senior researcher in multimodal biomedical imaging at the French Atomic Energy Commission (CEA) in the “Groupe d’Imagerie Neurofonctionnelle” of  “Institut des maladie neurodégénératives” UMR5293

Specialist in multimodal imaging, acquisition and cohort processing in brain imaging, his primary focus is on intrinsic connectivity observed in functional MRI in the resting state.  The second focus is on the development of new methodology in the analysis and management of bio-imaging data such as AAL (11K citation index) and the AICHA atlas, or resting network classification algorithm (MICCA).

Since 2012 he has developed in collaboration with the company Fealinx, a research axis on the management and processing of imaging data. This collaboration led to the creation in 2017 of a joint laboratory, Ginesislab (LABCOM ANR), whose research focuses on the application of learning and prediction methods using deep learning to imaging cohorts.

J. Korobelnik

Jean-François KOROBELNIK

Ophtalmologist, Bordeaux Hospital

Jean-François KOROBELNIK is professor of ophthalmology at the Bordeaux University Hospital since 1999, Head of Department since May 2013. He is involved in the Research focusing on the epidemiology of eye diseases (Consortium E3), on macula disorders. The care concerns retinal diseases treated medically or surgically (AMD, Retinal detachment, Membrane and macular hole...).

He is a member of the French Society of Ophtalmology (President from May 2013 to May 2015), the American Academy of Ophtalmology, the Association for Research in Vision and Ophtalmology, the American Society of Retina Specialists, Euretina, the Club Francophone des Spécialistes de la Rétine (President from May 2017 to May 2019) and the Club Jules Gonin (Executive committee member).

I. Bourdel-Marchasson


Gerontologist, Bordeaux Hospital

Isabelle Bourdel-Marchasson is professor of geriatric medicine since 2002 at the University of Bordeaux (UB). She received her MD from UB and qualified in geriatrics, internal medicine and endocrinology. She also received her PhD in the Center of Magnetic resonance in biological systems (CRMSB), after a master in nutrition.

Since 1990, she is medical practitioner in geriatric medicine at CHU of Bordeaux. She is the head of a post-emergency acute care geriatric unit and of the outpatient hospital dedicated to comprehensive gerontological assessment in frail older patients.

She is chair of the graduation program in geriatrics in Nouvelle Aquitaine and at the Island of Reunion and she drives an e-learning diploma of geriatric medicine.

Prevention of loss of functional independence is a priority to Prof Bourdel-Marchasson accross clinical, teaching and research activities. She has been PI of several randomized clinical trials of non-drug interventions in malnutrition, diabetes and cancer in the older. She is particularly involved in the field of diabetes in the older at an international level. She chairs the Special Interest Group Diabetes from EUGMS ( and she belongs to the European Diabetes in Older People Working Party (

H. Jacqmin-Gadda


Research Director, BPH Center UMR1219

Dr Hélène Jacqmin-Gadda, PhD, born in 1968, defended her thesis in 1993 and is a researcher in biostatistics at Inserm since 1996. She is Research Director of the Biostatistics team at the Inserm U1219 Bordeaux Population Health Centre since 1994.

Her main work is focused on the development of models for the analysis of longitudinal data and the occurrence of events in order to study the natural history, risk factors and progression of dementia in the elderly, especially in Alzheimer's disease and cognitive ageing.

The aim of her models is to take into account the characteristics of the disease and the tools for measuring cognition, as well as selection biases that may be particularly important in cohorts of elderly subjects. She is the author of more than 100 publications and co-author of the book "Dynamical Biostatistical Models".

F. Tison

François TISON

Neurologist, Bordeaux Hospital

François Tison (PU-PH, >260 publications, H-Index WOS: 53) is Professor of Neurology at Bordeaux University and consultant neurologist at the University Hospital of Bordeaux. He is coordinator of the Bordeaux Center of Excellence for Neurodegenerative disorders (BIND,, head of the Institute of Neurodegenerative Diseases-clinical branch (IMNc, and deputy director of the Institute for Neurodegenerative Diseases (IMN, CNRS UMR 5293-

He conducted his clinical and research career in the field of neurodegenerative diseases by exploring several disciplines from basic, clinical and translational research to epidemiology. He is PI on multiple academic, industry or foundation-sponsored clinical research studies on neurodegenerative disease. His current interest is focused on non-drug therapies based on the mindfulness in neurodegenerative diseases.

D. Tregouët

David-Alexandre TREGOUËT

WP2 Leader, Research Director, UMR1219

Born 27/01/1973, David-Alexandre Trégouët was recruited at INSERM as a research associate 2nd class in 1999 just after completing his PhD in statistical genetics.

Promoted 1st class Research Director in 2019, his expertise covers the developments and the applications of statistical and bioinformatics methodologies to disentangle the molecular epidemiology of cardiovascular diseases, with a strong focus on venous thromboembolism.

From 2014 to 2018, he has been heading the department of Genomics and Pathophysiology of Cardiovascular Diseases within the INSERM UMR_S 1166 at the ICAN Institute for Cardiometabolism and Nutrition on the Pitié-Salpêtrière Campus (Paris). His team was then composed of clinicians, molecular and cellular biologists, epidemiologists, statistical geneticists and bioinformaticians.

By the middle of 2018, he joined the Bordeaux Population Research Center ( to develop a research program on precision medicine in thrombotic disorders.

C. Longo Dos Santos


VP Clinical Operations, Qynapse

Dr. Clarisse Longo dos Santos, PhD, co-founder and VP of Product Management of Qynapse, is responsible for the tasks related to the development and use of the products, and is involved in the clinical validation of the medical device and the contact with partners.

She obtained her PhD in 2010, at Concordia University, Canada, using fMRI ; she has conducted post-doctoral research at Neurospin/CEA using diffusion MRI in neurological diseases.

She has worked at the CATI platform performing imaging analyses in data from patients with Alzheimer's disease before co-founding Qynapse. Her expertise is in neuroimaging, neuropsychology & clinical studies.

C. Delcourt


Research Director, BPH Center UMR1219

Cécile Delcourt has a PhD in statistics and public health and is senior researcher at Inserm U1219-Bordeaux Population Health Research Center, where she leads the LEHA (Lifelong Exposures, Health and Aging) research group.

She has a strong expertise in the epidemiology of eye diseases (in particular AMD, cataract and glaucoma). She is internationally renowned in the identification of risk factors for major eye diseases (in particular smoking, light exposure and nutrition).

She has been leading 2 major population-based epidemiological studies in the field, since 1995 (POLA and Alienor studies). She has founded and led from 2011 to 2018 the “European Eye Epidemiology” consortium, gathering 32 teams from 12 European countries, and is workpackage leader in two European projects (Eye-Risk and Sense-Cog), granted in the Horizon 2020 framework.

B. Mazoyer


WP1 Leader, Neuroradiologist UMR5293

Bernard Mazoyer is a professor of neuroradiology at the University Hospital and Faculty of Medicine of Bordeaux, and a senior researcher at the Institute of Neurodegenerative Diseases (IMN, CNRS, CEA, University of Bordeaux).

His current research focuses on the quantification of the sources of variability in brain morphology and function, and on the identification of early MRI markers of cerebral ageing, thanks to population neuroimaging combining MRI, psychometry and genomics. Bernard Mazoyer graduated from the Ecole Normale Supérieure de Cachan (mathematics, 1972-1976), holds a doctorate in biomathematics (1983) and medicine (1985) from the University of Paris. He did a post-doctorate at the Lawrence Berkeley Lab (USA) in the field of advanced medical imaging techniques, in particular PET and MRI (1984-1985).

He was then recruited by the French Atomic Energy Commission at the Orsay centre to direct the positron emission tomography programme and in particular the development of PET brain activation studies (1986-1990).

He was then elected Professor of Biostatistics and Medical Informatics at the CHU and at the Faculty of Medicine Paris 7 (1990-1997) while continuing to work with PET and MRI for the CEA.  In 1997, he moved to Caen as Professor of Radiology and Medical Imaging (1997-2012) and Director of the Cyceron multimodal biomedical imaging platform, which he will develop as a reference centre for translational imaging in the fields of neurology, cardiology and oncology. Since 2012, he is professor of neuroradiology at the Bordeaux University Hospital and senior researcher at the Institute of Neurodegenerative Diseases (CNRS, CEA, University of Bordeaux).

Bernard Mazoyer is a pioneer of brain imaging techniques and their applications to the study of the neural bases of cognitive functions under normal and pathological conditions. In 1989, he co-founded the GIN (, the first cognitive neuroimaging team in France, of which he was director until 2016.  He is also one of the pioneers of population-based neuroimaging, which enables the study of cerebral ageing through the analysis of very large multimodal databases.

He organised the 1st Conference on Brain Mapping in 1995 in Paris and was at the origin of the creation in 1997 of the Organisation for the Mapping of the Human Brain, of which he was the first elected president. Co-author of more than 350 scientific publications, his work has received more than 25,000 citations. He was elected a member of the Institut Universitaire de France in 2001, and received the Seymour Cray Prize in intensive digital computing (1993) and the Dagnan-Bouveret Prize of the National Academy of Moral and Political Sciences (2003).

A. Bikfalvi


Research Director, U1029 Inserm Center

Andreas Bikfalvi is an MD PhD with both scientific and clinical training. He is an exceptional class full Professor ("Professeur de Classe Exceptionnelle") and leads since more than 20 years a laboratory that is affiliated to INSERM and the University of Bordeaux (now Angiogenesis and Tumor Microenvironment Laboratory, INSERM U1029).

His main line of research is related to vascular biology (angiogenesis) and tumour biology, focusing on studies dealing with angiogenesis and with the cross talk between angiogenesis and tumour biology and, in particular, metastasis. He has  also developed unique in vivo models allowing large-scale genomic approaches and is also focused on mechanistical studies involving key players.

Besides, he is also working on specific aspects of developmental angiogenesis and has developed unique in vitro models based on artificial blood vessels which can be used for mechanistically and pharmacological studies.