Dr. Charest's research focuses on understanding the molecular mechanisms and signaling pathways controlling the directed migration of cells (chemotaxis), which is a key factor in tumor dissemination. She has been studying cellular signaling for 17 years and in the context of chemotaxis for 10 years. For this, Dr. Charest uses both human cells and the model organism Dictyostelium discoideum, which provides great genetics and biochemical advantages over human cells. Using Dictyostelium, her group investigates the signaling network and molecular mechanisms implicated in chemotaxis. They collaborate with Wouter Jan-Rappel at UC San Diego to generate mathematical models of the chemotactic pathways and use them to predict the signaling network’s architecture and guide their investigation.
In addition, Dr. Charest's group recently started investigating whether discoveries made with Dictyostelium apply to cancer cell migration and began collaborating with UACC member Ghassan Mouneimne who is working on breast cancer cell biology and migration. In addition, in collaboration with, they measure protein-protein interaction dynamics. Their approach is collaborative and multi-disciplinary and provides unique insight into the mechanisms cells use to migrate in response to chemoattractant signals.
Our research focuses on the signal transduction pathways and molecular mechanisms controlling directed cell migration, or chemotaxis, in eukaryotic cells. Chemotaxis is central to many biological processes, including the embryonic development, wound healing, the migration of white blood cells (leukocytes) to sites of inflammation or bacterial infection, as well as the metastasis of cancer cells. Cells can sense chemical gradients that are as shallow as a 2% difference in concentration across the cell, and migrate towards the source of the signal, the chemoattractant. This is achieved through an intricate network of intracellular signaling pathways that are triggered by the chemoattractant signal. These pathways ultimately translate the detected chemoattractant gradient into changes in the cytoskeleton that lead to cell polarization and forward movement. In addition, many cells such as leukocytes and Dictyostelium, transmit the chemoattractant signal to other cells by themselves secreting chemoattractants, which increases the number of cells reaching the chemoattractant source.
To investigate key mechanisms of signal transduction underlying chemotaxis, we are using the social amoeba Dictyostelium discoideum as well as human cancer cell models. Cell motility and chemotaxis of Dictyostelium cells is very similar to that of leukocytes and cancer cells, using the same underlying cellular processes as these higher eukaryotic cells. Dictyostelium is amenable to cell biological, biochemical, and genetic approaches that are unavailable in more complex systems. The discoveries we make using Dictyostelium are then confirmed in human cells and, in particular, in the context of directed cancer cell migration and metastasis. Our aim is to understand the molecular foundation of directed cell migration, which is expected to guide the design of efficient anti-metastatic treatments.
Our approach is interdisciplinary, in which we combine molecular genetics and proteomics to identify new signaling proteins and pathways involved in the control of chemotaxis, with live cell imaging using fluorescent reporters to understand the spatiotemporal dynamics of the signaling events, as well as biochemical analyses and proximity assays [including Bioluminescence Resonance Energy Transfer (BRET) and FRET] to understand how proteins interact and function within the signaling network. In addition, in collaboration with Dr. Wouter-Jan Rappel at UC San Diego, we generate quantitative models of the chemotactic signaling networks to help identify key regulatory mechanisms and link them to whole cell behavior.
American Cancer Society Scholar, 2015-2019
Fonds de la Recherche en Sante du Quebec post-doctoral fellow, 2005-2008
Heart and Stroke Foundation of Canada graduate fellow, 2001-2004
Fonds de la Recherche en Sante du Quebec graduate fellow, 2001-2003
Canadian Hypertension Society graduate fellow, 1999-2000