ELEANOR

Our research program relies on major components:

• Large-scale epidemiological and clinical cohorts coupled with biosamples;
• The deployment of cutting-edge high-throughput technologies for deep molecular phenotyping;
• The application of advanced statistical methodologies;
• A group of experts in molecular-clinical epidemiology;
• A widespread network of collaborators that enables us to contribute to the functional characterization of the identified biomarkers.

Our project is focusing on three inter-related clinical outcomes, cognitive impairment / dementia, stroke, and thrombosis and is organized around 4 themes:

• Molecular epidemiology of vascular brain aging, (PI: Stéphanie Debette).
  Using collaborative genome-wide association study meta-analyses and next generation sequencing data we are studying the genetic underpinnings of stroke and MRI-markers of covert cerebral small vessel disease (SVD). We have a growing interest in cross-ancestry studies, as these are crucial to enhance genomic discovery and make results more representative. Through the ERC SEGWAY we are taking a lifespan approach to explore early determinants of brain aging and the impact of genes predisposing to stroke, dementia and SVD on brain microstructure in young adults (i-Share cohort). In the RHU SHIVA project (national investment for the future funding), following up on efforts that we initiated in the EU-JPND BRIDGET program, we are now expanding our explorations to other omics approaches (epigenomics, transcriptomics, proteomics and metabolomics), focusing in particular on deciphering the molecular underpinnings of covert SVD and its contribution to stroke and dementia. Finally, we are engaged in leveraging these molecular epidemiology studies to accelerate drug discovery and improve risk prediction/stratification for targeted prevention. Our group is also involved in European therapeutic guideline coordination.
• Exposome of brain aging and dementia (PI: Cécilia Samieri).
  The network and dynamics of environmental factors leading to age-related brain diseases has yet to be elucidated, in order to identify the most impactful targets for prevention. This exposome research axis leverages molecular epidemiology, brain imaging and advanced statistical approaches deployed to population-based cohorts with biobanks in order to investigate: (1) the exposome of brain health at key ages, and (2) the underlying pathways and life-course dynamics. The general aims are to: refine assessment of already-known exposures (eg, diet biomarkers); explore novel exposures (eg, chemical mixtures); investigate beyond individual exposures (eg, microbiome interactions); and eventually model the global exposome network, to improve etiological modeling of age-related brain diseases. We will capitalize on existing data (e.g. the 3C cohort) and target younger populations, building a new population-based cohort of 2000 participants aged 55-80 years from the community living in Bordeaux metropole, the B cube (Biobank and Brain Health in Bordeaux) study.
• Precision Medicine for better prophylaxis & better knowledge in venous thrombosis (PI: David-Alexandre Trégouët).
  After spending several years to identify common genetic factors for venous thrombosis (VT) in the general population, we are now embarking into a more integrative analysis of various molecular determinants (genes; epigenetic marks, proteins,…) on specific subgroups of individuals at higher risk of VT including women under oral contraceptives, patients with a previous history of VT and patients with viral infections.
  In parallel, building on our recent successes, we will continue our genetic investigations of rare forms of unexplained inherited VT through the application of whole exome/genome sequencing in familial cases.
• Integrative approach for vascular and brain disorders (all PIs).
  The deep characterization and understanding of the biology of a complex disease requires to integrate results/data from others diseases as they very often share common risk factors and pathophysiological mechanisms. By capitalizing on the existence of complementary and synergistic expertise and bioresources brought by ELEANOR’s PIs in different but interrelated diseases, we are implementing an integrative research strategy to optimize the identification and the characterization of molecular determinants associated with some of the most common age-related diseases.