Functional genomics of brain disease : linking regulatory mechanisms, circulating immune states and clinical trajectories

Résumé :

My research uses func-onal genomics to characterize disease associated molecular states and to understand how they relate to biological mechanisms, clinical heterogeneity and patient trajectories. I first used functional genomics directly in human brain tissue to identify regulatory alterations associated with disease. In autism spectrum disorder, genome wide profiling revealed that clinically and genetically heterogeneous patients nevertheless shared convergent changes in regulatory activity. Subsequent studies in other brain disorders showed that this convergence at the molecular level was a recurrent feature and established functional genomics as a powerful approach to resolve disease-associated regulatory states. I subsequently extended this approach to circulating cells, with the objective of accessing disease associated molecular states in living patients. In severe brain injury and psychiatric disorders, our studies identified
immune and regulatory signatures associated with clinical trajectories and disease severity. These results support the use of circulating immune states to characterize biological heterogeneity beyond conventional diagnostic categories and provide a basis for patient stratification. A complementary programme in genetically defined neurodevelopmental disorders allows us to investigate these molecular alterations in a causal framework. By profiling patient blood cells carrying pathogenic variants in chromatin and proteostasis regulators, we can connect a defined genetic alteration to its molecular consequences and to disease-relevant cellular pathways.

Together, these studies establish a func-onal genomics framework that links regulatory mechanisms to accessible biomarkers and clinical trajectories in neurological and psychiatric disease.

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Contact : yury.lages@univ-grenoble-alpes.fr ou sebastien.carnicella@univ-grenoble-alpes.fr