CV Science

LEILA MAOUCHE CHRETIEN PhD Biomedical Researcher

Course and current status

Since 2016  

Group leader (CRCH-INSERM); Imagine institute, Paris

Topic: Mastocytosis disease and Stem cells.

Multi-thematic team leader: Pr Olivier Hermine

Director of the institute: Pr Stanislas Lyonnet

 

2008-2016    

Group leader - iMETI/STI-UMR-E 007. CEA Fontenay-aux Roses

Topic: Disease modeling, iPS cell-based therapy and Gene therapy. 

 Director: Pr Philippe Leboulch.

 

2006-2008       

PI of a research project. Cochin Hospital, Paris

Topic: Embryonic and adult hematopoietic stem cells

Director: Pr Pierre-Olivier Couraud

 

2004-2006     

Scientist at Harvard Medical School. Boston 

- Division of Pediatric Hematology/Oncology, Children's Hospital, Harvard Stem Cell Institute

Topic: Embryonic stem cells and hematopoietic tissue engineering.

Director : Pr George Q. Daley

- Department of Genetics NRB, Brigham and Women's Hospital.

Topic : Gene therapy of beta thalassemia 

Director : Pr Philippe Leboulch

 

2000-2004     

PI of a research project. Cochin Hospital, Paris

Topic: Adult stem cells and Leukemia 

Director: Pr Axel Khan.

 

1994-2000      

Postdoctoral fellow and Junior scientist (CR2). Henri Mondor hospital, Créteil

Topic: Hematopoiesis, erythropoiesis and leukemia.

Director : Dr PH Roméo.

 

1990-1994       

PhD program: EFS, Paris

Topic: Epo-R gene cloning and regulation in erythropoiesis.

Scientific summary

Throughout my scientific career, I have focused on uncovering the mechanisms that regulate different lineages of normal and leukemic hematopoiesis, while also developing innovative therapeutic strategies.

During my PhD, I conducted research on erythropoiesis and cloned the human Erythropoietin receptor gene and deciphered its regulation in red cells. I then joined Paul Henri Roméo's lab as a post doc and developed molecular innovative approaches that led us to clone the first SCL/TAL1 target gene in red cells and to discover its binding to DNA via a multi-factorial complex. After my recruitment at INSERM as a young scientist, I pursued my work on SCL and demonstrated its inability, alone, to induce T-ALL unlike what was initially thought. Additionally, I was involved in setting up the molecular biology lab of the anathomopathology service at Henri Mondor hospital, working on B cell lymphoma. We cloned a new gene and identified a prognostic marker involved in diffuse large B cell lymphoma (LDGCB) and Mediastinal B-Lymphoma, respectively.

In 2004, I was awarded an INSERM/HARVARD Medical School interface contract. I first started in the US Philippe Leboulch’s Lab working on gene therapy before to join George Daley lab to acquire expertise on pluripotent stem cells (hESCs-mESCs) and to develop projects on tissue engineering.

Upon returning to France, I joined the "Innovative Therapies" Department headed by P. Leboulch and set up a regenerative cell therapy group. My expertise in pluripotent stem cells led me to assess the potential of iPSCs to produce hematopoietic cells for therapeutic purposes and to evaluate their capacity of reconstitution in vivo. I derived iPSC from the first beta thalassemia patient, successfully treated by gene therapy by P. Leboulch, to compare gene therapy and regenerative therapy in  the context of thalassemia, in collaboration with several international groups.

My expertise in iPSCs has attracted teams working on non-hematopoietic diseases such as Gerard Tachdjian's team at Beclère hospital, to study the causes of male infertility, and Anne-Dubart's team at Paul Brousse hospital, to carry out liver regeneration for therapeutic purposes.

In 2016, I moved to IMAGINE Institute to lead a group on mastocytosis in Olivier Hermine lab, head of the hematology service. My group focus on searching mutations/deregulations cooperating with to the frequent mutations in KIT receptor to explain the physiopathology of this heterogenous disease and to identify new therapeutic targets.

We discovered inherited mutations deregulating the hedgehog (Hh) signaling pathway in familial cases of mastocytosis, and demonstrated that the combination of tyrosine kinase and Hh inhibitors improved the survival of a murine model of aggressive mastocytosis. We are currently deciphering the role of other mutations uncovered in additional families to explain the resistance to tyrosine kinase inhibitor treatment and to propose personalized therapeutic strategies.

I hold prominent positions within the scientific community, serving as a board member for the French Society for Stem Cell Research (FSSCR), the French Society for Cell and Gene Therapy (SFTCG), and as the scientific Referent of the National Reference Center for Mastocytosis (CEREMAST). My roles demonstrate my dedication to advancing scientific research in various fields, including stem cells, gene therapy, and mastocytosis.