Molecular mechanisms of renal lineage specification and cancer
Understanding how genes regulate embryogenesis is vital to development and cancer. Pax protein family is involved in regulating organ development as well as in cancer progression. Pax2/8 genes are found to regulate renal specification and morphogenesis in space and time. They act on key developmental processes such as cell commitment, mesenchymal-epithelial transition and epithelial tissue elongation. In the past, we have made important advances on urogenital system morphogenesis and narrowed down outstanding biological question of which factor first activates Pax2 in nephric field of the intermediate mesoderm. Pax2 not only acts as the key regulator of the renal progenitors by establishing a lineage-restricted transcriptional program but also is a sensitive and specific marker of metastatic clear cell renal cell carcinoma (CC-RCC). We believe Pax2 is upregulated by similar developmental switch in both development and cancer. Hence we focus on identifying the upstream signals that drive Pax2 regulation.
Our goal is to identify the developmental pathway and more specifically the factor that initiates specification of renal lineage. The main focus of this project is to dissect the molecular mechanisms involved in renal fate specification during development to study CC-RCC. The idea is to understand how cells are driven to a specific fate during development. This will shed light on the developmental pathways that exert control on cell homeostasis during embryogenesis and tumorigenesis.
Department of Biochemistry, McGill University
PhD Student, Laboratory of Dr. Maxime Bouchard