Drugging GTPases Beyond KRAS
Flash Talk with Guest, Johannes Morstein, Ph.D.
Hosted by Drug Hunter's Director of Industry Research & Relations Dennis Koester, Ph.D.
November 7, 2024 at 8 AM PDT / 11 AM EDT / 5 PM CEST
The family of Ras-like GTPases consists of over 150 different members, regulated by an even larger number of guanine exchange factors (GEFs) and GTPase-activating proteins (GAPs). These comprise cellular switch networks that govern cell motility, growth, polarity, protein trafficking, and gene expression. Efforts to develop selective small molecule probes and drugs for these proteins have been hampered by the high affinity of GTP and lack of allosteric regulatory sites. This paradigm was recently challenged by the discovery of a cryptic allosteric pocket in the Switch II region of KRAS.
In this Flash Talk, Johannes Morstein will discuss the question if similar pockets are present in GTPases beyond KRAS. He will detail how the team systematically surveyed members of the Ras-, Rho-, and Rab-family of GTPases and found that many GTPases exhibit targetable Switch II pockets. He will explain the notable differences in the composition and conservation of key residues. Johannes will detail how these findings set the stage for the development of optimized inhibitors for many members of this previously undruggable family.
Johannes Morstein studied chemistry and biochemistry at the LMU in Munich and the University of Glasgow in Scotland. He gained his first research experience as a visiting researcher with Chris Chang and John Hartwig at UC Berkeley. In 2021, he completed his PhD with Dirk Trauner at NYU. There he developed photoswitchable lipids that enable the precise spatiotemporal control of lipid biology and metabolism in cells and in vivo. After his PhD Johannes joined Kevan Shokat’s group at UCSF as a NIH postdoctoral fellow. There he worked on expanding the druggability of GTPases, long considered 'undruggable' targets. Upon completion of his postdoctoral studies in 2025, Johannes will join Caltech CCE as an Assistant Professor. His group will work on Lipid and Membrane Chemical Biology.
Don't miss this opportunity to learn about how researchers are breaking into previously undruggable space leveraging innovative analytic technologies. Johannes will also be available for a Q&A session. So be sure to bring your questions about drugging ‘undruggable’ proteins in the GTPase family. This is a live-only event you won't want to miss!