Education and Training
Postdoctoral Research Fellow, Joyner lab, Sloan Kettering Institute
Ph.D. Molecular, Cellular and Developmental Biology, C. SOULA lab, “Centre de Biologie du Dévelopement”, Paul Sabatier University, Toulouse III, FRANCE. (supervisor: Dr. Bruno GLISE).
Masters, Molecular, Cellular and Developmental Biology, Paul Sabatier University, Toulouse III, FRANCE
BS, Biochemistry, Molecular Biology, Nantes University, FRANCE
Medulloblastoma (MB) is the most common malignant brain tumor in children and over one-third of children with MB die within 5 years of diagnosis. The majority of MBs arise from granule cell progenitors (GCPs) within the cerebellum, with approximately 25 percent originating from mutant cells with aberrant activation of the Hedgehog (HH) pathway, a key developmental pathway that regulates normal development of many cell types including GCPs.
Over the past decade, several mouse genetic models of the HH subtype of MB have been generated. However, although mouse models for MB with mutations in the HH pathway have been critical tools for identifying the cell of origin of MBs, an experimental approach is required to determine the cellular and genetic mechanisms underlying tumor progression and heterogeneity. Moreover the induction of mutations in most GCPs in these murine models does not model sporadic tumors and the relative contribution of cells of the tumor and microenvironment has not been well characterized. In addition, as inhibition of HH signaling can not be used in children due to severe bone defects and adults develop resistance to HH antagonists, critical genes regulated by HH signaling need to be identify as they may represent putative therapeutic targets.
The goals of my project are two-fold: 1) Analyze the effect of altering the level of HH signaling on GCP behaviors and model sporadic MB using a novel genetic mosaic method developed in lab called MASTR (mosaic analysis with spatial and temporal control of recombination); 2) Identification of downstream transcriptional targets of Gli2 (the main HH signaling transcriptional activator) that could alter tumor outcome.