Fernando SEPULVEDA and Gaël MÉNASCHÉ

Our research lies at the intersection of immunology, cell biology, and genetics. Our goal is to identify the pathophysiological mechanisms underlying severe disruptions in immune homeostasis by studying immune disorders caused by genetic defects. This approach offers unique opportunities to characterize key physiological processes, understand complex mechanisms, and develop new diagnostic and therapeutic tools.
 

In this context, we are pursuing two main lines of research:

• Unraveling the genetic causes of hemophagocytic lymphohistiocytosis (HLH)

HLH presents a unique immunological phenotype characterized by the uncontrolled expansion of activated polyclonal CD8+ T lymphocytes and macrophages. Over the years, we have made significant contributions to establishing a link between genetic defects affecting lymphocyte cytotoxic activity and the development of HLH. However, several hereditary cases of HLH without impaired lymphocyte cytotoxicity suggest that defects in other regulatory pathways may contribute to the development of HLH. The goal of our research is to understand these new immunoregulatory mechanisms essential for maintaining immune homeostasis by identifying new genetic defects responsible for cases of HLH in which lymphocyte cytotoxic activity is normal.

• Identification of new molecular determinants that regulate allergic responses

Allergic reactions result from an inappropriate immune response to harmless antigens known as allergens. Although we now have a better understanding of the development of allergic diseases, it has become clear that various mechanisms involving multiple immune and non-immune processes, inflammatory pathways, and signaling pathways in effector cells underlie the development of allergic diseases.  With the goal of discovering new molecular effectors of the allergic response, our research project focuses on two main aspects: 1) deciphering the molecular mechanisms regulating mast cell degranulation, and 2) understanding extremely severe allergic diseases at the genomic and transcriptomic levels.