"Identifying Druggable Pockets Using Systematic Cysteine-Scanning"

                                                                               All Welcome

Host: Professor Alessio Ciulli 

Venue: Sir Kenneth and Lady Noreen Murray Seminar Room, CTIR 2.84 

Abstract:

 The landscape of cancer therapeutics has largely been confined to kinase catalytic domains. To expand the reach of therapeutics into new classes of therapeutic targets, we need to identify and validate specific mechanisms and pockets to enable drug discovery.  To enable this, we have developed a method called CysMAP for identifying druggable pockets in proteins of interest. Through screening of cysteine-variant libraries against tailored covalent small molecule libraries, CysMAP has successfully confirmed known pockets in KRAS and unveiled novel actionable ligand-bound conformations. Our approach, validated by structural analyses and functional screens in cancer cells, demonstrates the ability to distinguish compounds that selectively bind to specific protein variants. This technology holds promise for advancing drug discovery efforts against challenging targets like the RAS protein family, offering new personalized cancer treatment strategies.

 Bio:

 Moore van Tienen’s research is focused on developing novel therapeutic strategies in cancer by integrating functional genetic and chemoproteomic tools. He earned his PhD at the MRC Laboratory of Molecular Biology in Cambridge with Mariann Bienz, where he studied protein-protein interactions within the Wnt signaling pathway. He has extended his research as an EMBO postdoctoral fellow at the Broad Institute of MIT and Harvard, under mentorship of William Sellers, by devising methods to identify druggable pockets on oncogenic proteins. His efforts in developing new methods to systematically screen these targets against covalent compounds have uncovered potential novel binding conformations in RAS mutants, offering new avenues for the development of inhibitors.