Isabelle André

The common denominator of our project is the human lymphohaematopoietic system, characterized by cells with differing self-renewal and differentiation capacities as a function of the individual's age and clinical status (i.e. healthy or diseased). In adult mammals, haematopoiesis (i.e. the expansion and differentiation of haematopoietic stem cells into blood cells in the bone marrow) undergoes constant, tightly regulated renewal and undergoes profound changes over the lifespan.

Understanding of the hierarchy of human haematopoiesis and the different steps in T and B cell differentiation in the healthy body and in very particular disease situations constitutes the most fundamental part of our research project. To lead our research, the human lymphohematopoiesis laboratory has access to a cohort of patients involved in phase I/II gene therapy clinical trials and also a cohort of patients with hereditary immune deficiencies associated with B cells.  Overall, the knowledge generated by these studies will help us to actively implement new treatment protocols. Haematopoietic stem and progenitor cells (HSPCs) harvested from a healthy or diseased individual and ex vivo gene modifications constitute essential tools for curing most severe, cell-intrinsic, inherited defects of the lymphohaematopoietic system. Nevertheless, several issues still compromise the full success of these types of therapies.

Improvements in this HSPC-based strategy have resulted from progress and discoveries provided by the first part of our project and by other research groups. The most recent findings on the characteristics of human T cells (i.e. their long life, self-renewal capacity, homeostasis and functions) have prompted us and others to consider their in vivo use after ex vivo manipulation - paving the way for less toxic therapeutic approaches.