Welcome on the Necker-Enfants Malades Institute website
Sophie Ezine: I earned my PhD degree from the University Paris 6 (UPMC) and then performed a postdoctoral fellowship. I trained at the department of Pathology (Stanford Medical center, USA) with Pr Irving L. Weissman. From then I became interested in T cells and more specifically, their origin. My scientific domains are: hematopoietic stem cell transplantation and T cell commitment, T cell differentiation and migration of bone-marrow progenitors to the thymus.
Flora Zavala: I earned my PhD degree from Paris 11 University and then performed my post-doctoral training at the department of medicinal chemistry of Kyoto University, Japan, with Pr. Osamu Hayaishi. From then, I became interested in immunology and particularly neuroimmunology. My present scientific domains are focused on the role of hematopoietic growth factors and progenitors in the regulation of autoimmune and allogeneic immune responses.
At the apex of the hematopoietic hierarchy, hematopoietic stem cells (HSCs) self-renew to maintain lifelong hematopoiesis. As HSCs differentiate, they upregulate Flt3 cytokine receptor expression to generate non-renewing multipotent progenitors (MPPs). The identification of downstream developmentally restricted progenitors, such as IL-7Rαhi common lymphoid progenitors (CLPs) established that development of related cell lineages proceeded via lineage-restricted intermediates. The mechanism by which some descendants of HSCs differentiate into lymphoid progenitors is not well understood but may involve signals from the bone marrow niche, cytokines, and transcription factors (SE).
Recent studies in mice and humans have significantly expanded the lymphocyte family from adaptive lymphocytes and NK cells to include several additional innate lymphoid cell (ILC) types. Much evidence supports the derivation of ILCs and T cells from lymphoid progenitors. Adoptive transfer experiments have shown that LMPPs and CLPs generate not only T and B cells, but also ILCs (MC). The possible feed-back control on immune responses of hematopoietic progenitor sub-populations emerging in adaptive hematopoiesis taking place in infectious and inflammatory conditions also warrants further investigation (FZ).
Finally, the study of rare circulating cells is implemented for the detection of foetal cells for non-invasive prenatal diagnostics of trisomy 21, and detection of circulating cancer cells, whose propagation in blood represents a key step in the metastasis formation process (PPB).
BM transplants are expected to ensure continuous blood cell production in patients with hematological diseases and to correct congenital defects or acquired autoimmune disorders. The choice of cells to be transplanted is of major importance. Multipotent precursors from the bone marrow (BM) home to the thymic environment, which induces their entry into the T-lineage program. In the objectives to identify the early thymic events following BM grafts, in vivo and in vitro approaches associated with molecular analysis are performed.
RORγt+ innate lymphoid cells (ILC3) play a fundamental role in the development of lymphoid tissues as well as in the homeostasis and defense of mucosal tissues. Deregulation of ILC3 is associated with inflammatory pathology. Our first aim is to characterize ILC3 progenitors and function at the steady state and during intestinal inflammation. Our second aim is to assess the impact of the cross talk between ILCs and T cells on ILC homeostasis and stromal cell function.
Infections and inflammation trigger an emergency hematopoiesis aiming at replenishing the immune system with cells that can effectively contribute to immune defense. We hypothesized that the control of potentially deleterious immune responses and of excessive inflammation that may result in chronic immune diseases might be exerted by the emerging hematopoietic progenitor subsets endowed with immunoregulatory properties. We aim to characterize such regulatory progenitors.
Using immune-cytopathological analyses and high throughput sequencing of single cells, we aim at studying the entire informative potential of circulating cancer cells (CCCs), notably for theranostic purposes, guiding therapeutic choices based on thorough understanding of biological parameters impacting the efficacy of targeted anticancer treatments. A second objective is to develop a reproducible test for as an alternative to amniocentesis and chorionic villous sampling for non-invasive pre-natal diagnosis.
