Complexities in RAS GTPase Signalling to Effector Proteins

Matthew J. Smith, PhD

Associate Professor
Department of Pathology and Cell Biology
Université de Montréal

Principal investigator
Cancer Signalling and Structural Biology Research Unit
Institute for Research in Immunology and Cancer

Smith Lab

This conference is hosted by Jean-François Côté, PhD. This conference is part of the 2022-2023 IRCM conference calendar.

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In person: 
IRCM Auditorium
110, avenue des Pins O, H2W 1R7 Montreal

Online:
Zoom Link : https://zoom.us/j/95269762104
ID : 952 6976 2104
Code : 476372

IRCM conferences are set to occur under a hybrid format. However, please note that last-minute changes to online-only lectures may occur due to unforeseen circumstances. We invite you to visit this webpage again a few days before attending.

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About this conference
RAS small GTPases play a fundamental role in development and drive an extraordinary number of human cancers. Over three decades of study have failed to wholly characterize pathways stimulated by activated RAS, driven by direct engagement with ‘effector’ proteins that have RAS binding domains (RBDs). Current dogma relies heavily on sequence homology due to a lack of basic biochemical data describing most interactions. The well-studied HRAS, KRAS and NRAS GTPases are part of a 35-member subfamily of RAS proteins that are highly evolutionarily conserved. For most of these GTPases there are no data describing how or when they adopt an activated conformation, their position in intracellular networks, or binding specificity towards 50 putative RAS effectors with RBDs. My lab is working to provide a new paradigm for signaling downstream of RAS by characterizing the structure and function of this complete small GTPase subfamily. This talk will focus on two enigmatic RAS effectors that distinctively govern tumour suppressor pathways, AFDN and RASSF, and a cautionary tale for studying small GTPase activity derived from our work on the MRAS homolog.
 

About Matthew J. Smith
Dr. Matthew James Smith is an Associate Professor in the Department of Pathology and Cell Biology at Université de Montréal, and a Principal Investigator at the Institut de recherche en immunologie et en cancérologie (IRIC), where he leads the Cancer Signalling and Structural Biology Research Unit. His research program aims to provide a mechanistic understanding of aberrant signalling in oncogenic RAS-transformed cells to both known and newly identified downstream partners and pathways. To do so, his team strives to develop new biophysical tools to understand small GTPases and their interactions with cellular proteins. 

Dr. Smith has published his work in several high impact journals, such as Nature Communications, Nature Chemical Biology, and Science Signaling. He was awarded a Tier II Canada Research Chair in Cancer Signalling and Structural Biology, recently renewed until 2027, as well as several research grants, namely from CIHR, NSERC, the Cancer Research Society (CRS), and the New Frontiers Research Fund (NFRF).
 

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