Pathophysiological processes linked to GBA1 mutations

Study of the Pathophysiological Mechanisms Associated with GBA1 Mutations (Gaucher Disease and Dementia with Lewy Bodies)

Investigators: Mélanie Franco (Associate Professor), Ali Tawbeh (post-doctorate), and Djonkounda Dembele (PhD student).

We investigate the pathophysiological mechanisms underlying diseases associated with GBA1 mutations, such as Gaucher disease (GD), by studying blood cells, particularly those of the erythroid lineage. GD is caused by bi-allelic deficiency of glucocerebrosidase (GCase), leading to sphingolipid accumulation, abnormalities in macrophages and red blood cells (RBCs), anemia, and inflammation. Our main objectives are to:

i)                characterize the molecular basis of erythroid and RBCs abnormalities;

ii)              decipher the pathophysiological mechanisms involving erythroid cells that contribute to GD symptoms; and

iii)              identify novel biomarkers and therapeutic targets.

In collaboration with Dr. François Mouton-Liger (Université Paris Cité, UMRS_1144), we also explore the impact of GBA1 mutations on the pathophysiology of Dementia with Lewy Bodies (DLB). DLB is a neurodegenerative disorder characterized by α-synuclein aggregation and neuroinflammation. Heterozygous GBA1 mutations are the strongest known genetic risk factor for DLB, suggesting shared mechanisms between DLB and GD. Investigating the pathophysiological processes linked to GBA1 mutations in DLB is our most recent line of research, aimed at uncovering novel insights and identifying new biomarkers.

Current collaborations: Physicians of the Centre de Références des maladies lysosomales (Hôpital Beaujon) - Dr Marine de Person, laboratoire de Chimie Analytique de l’ICP (UMR-CNRS 8000, Paris-Saclay) - Pr Pierre Buffet and Dr Alioune Ndour (U1134 BiOTiGR Team, UPC) - Pr George Karniadakis (Brown University, US) - Dr François Mouton-Liger and Pr Claire Paquet (UMR-Inserm U1144, UPC)

Previous collaborations: Pr Olivier Hermine, Dr Jean Benoît Arlet - Dr Zoubida Karim