Journal of Proteomics & Bioinformatics
Open Access
ISSN: 0974-276X
ISSN: 0974-276X
Sudhir Sahasrabudhe1,2
1University of Utah, USA 2Rines Therapeutics, USA
Posters-Accepted Abstracts: J Proteomics Bioinform
Proteomics technologies are revolutionizing the speed and depth of novel drug discovery. I will describe 2 examples: Example 1: A chemi-proteomics platform was used to capture and identify proteins that bind to small molecule hits from a cell-based genetic screen. This screen was geared to identifymolecules that are selectively lethal to cells with aberrantly active RAS-signaling pathway. This approach resulted in identification of several novel cancer targets and paved the way for creation of a novel small molecule currently in clinical Proof-of-concept (Phase 2a) studies in cancer patients. Example 2: Huntington�s disease (HD) is a fatal neurodegenerative condition caused by expansion of the polyglutamine tract in the Huntingtin (Htt) protein. Neuronal toxicity in HD is thought to be a consequence of protein interactions involving mutant Htt. We therefore hypothesized that genetic modifiers of HD neurodegeneration should be enriched among Htt protein interactors. To test this idea, we identified a comprehensive set of Htt interactors using two complementary approaches: High-throughput yeast two-hybrid screening and affinity pull down followed by mass spectrometry. This effort led to the identification of 234 high-confidence Htt-associated proteins, 104 of which were found with the yeast method and 130 with the pull downs. We then tested an arbitrary set of 60 genes encoding interacting proteins for their ability to behave as genetic modifiers of neurodegeneration in a Drosophila model of HD. This presentation will outline the identification and validation of novel drug targets for HD.
Email: rinesco@gmail.com