Mécanismes moléculaires régulant l'homéostasie et la tumorigenèse intestinale

 

Alex Gregorieff

Institut de recherche du Centre universitaire de santé McGill

 

Domaine : cancer

Programme Chercheurs-boursiers - Junior 2

Concours 2019-2020

Much of our understanding of the mechanisms underlying tumour growth and dissemination has come from studies examining the processes regulating normal embryonic development and tissue homeostasis. Indeed it is now well appreciated that tumours share many characteristics with normal developing and regenerating tissues. In particular, tumours like certain tissues are organized hierarchically with subpopulations of highly proliferative stem cells and differentiated cells with more limited proliferative potential.

Furthermore, cancer cells depend on growth factor stimulation from the surrounding microenvironment, which is reminiscent of stem cell niche found in several tissue types. In this proposal, I am interested in dissecting the signals regulating adult stem cells residing in the lining of the gastro-intestinal tract and determining how these molecular pathways contribute to colorectal cancer initiation and progression. In particular, I am investigating how key transcription factors driving maintenance of normal ISCs, namely the Hippo effectors, Yap and Taz, are implicated in intestinal stem cell dynamics, as well as in metastatic colorectal cancer.

The goal of these studies will be to identify vulnerabilities within tumour cells that may be targeted for anti-cancer therapy.