Grant: Canada Research Chairs

Our work focuses on important protein families that control cellular signalling required for the cytoskeletal dynamics events that orchestrate cell migration and invasion. The are key biological processes at the root of cancer progression to metastasis. Our research program is divided into 3 areas. First, we are interested to gain the fundamental knowledge of the molecular networks and the molecular mechanisms that contribute to cytoskeletal dynamics. These research efforts are focused on the RAS-family of proteins, such as the RHO and ARF subfamilies, and rely on proximity labeling approaches to reveal their interactomes at high-throughput. Combined with powerful functional studies, these efforts have led to important discoveries of mechanisms controlling cytoskeletal dynamics and cell migration and invasion. Second, we study the normal biological functions of these molecules such that we can better understand how they contribute to cancer progression. We have found that a number of the proteins studied above regulate a basic biological process known as cell-cell fusion. This includes RHO-family proteins and their regulators, and a number of their accessory proteins. This is a central biological function allowing to the building blocks of our muscles, the myoblasts, to unite their cellular membranes to form multi-nucleated cells. Our efforts exploit molecular, cellular and in vivo approaches, and are currently centered on defining the precise cytoskeletal-drive mechanisms regulating cell fusion. Third, we have developed a broad approach to study the cellular and molecular processes that contribute to breast cancer metastasis. This includes functional studies in breast cancer cells and the development of mouse models that can answer the contributions of our specific new genes to metastasis. We study the roles of kinases and cytoskeletal regulators. Our goal is to attempt to understand breast cancer cells behavior as they navigate through the metastatic cascade. This includes when leaving the primary tumours and invading secondary organs, but also how they integrate and survive into the new foreign environment to form micro- or macro-metastases. Our work will contribute important new basic mechanistic information on the signalling networks that contribute to normal cell biology and to cancer metastasis. This knowledge is needed to develop the new and much needed innovative therapies aiming at limiting cancer spreading, a serious health threat.