Michelle Arkin
Professor
Univ. of California, San Francisco
Talk Information
Disease-Focused Peptide Discovery
16 June 2025, 10:30am - 10:55am, in the Pacific Jewel Ballroom
L07 – Peptide/protein Complexes as Models for Protein/Protein Interactions in Drug Discovery
Professor Michelle R. Arkin is the Thomas William and Frederick John MacWilliam Distinguished Professor and Chair of the Department of Pharmaceutical Chemistry at the University of California, San Francisco, UCSF. She also serves as the Executive Director of the Small Molecule Discovery Center, SMDC, where she leads interdisciplinary efforts to develop chemical tools and drug leads targeting challenging biological processes.
Academic Background
Dr. Arkin earned her B.A. in Chemistry from Bryn Mawr College and her Ph.D. in Chemistry from the California Institute of Technology, where she conducted research under Professor Jacqueline Barton. She completed a Damon Runyon postdoctoral fellowship at Genentech, focusing on protein-protein interactions. Prior to joining UCSF, she was a founding scientist at Sunesis Pharmaceuticals, contributing to the development of inhibitors for IL-2/IL-2R and LFA1/ICAM, including the anti-inflammatory drug Lifitegrast.
Research Focus
Professor Arkin's research centers on developing innovative methods and molecules to target "undruggable" proteins, such as protein-protein interactions and intrinsically disordered proteins. Her lab employs biophysical techniques, including fragment-based drug discovery and high-content imaging, to identify and optimize chemical probes. These efforts aim to elucidate complex biological pathways and advance therapeutic strategies for diseases like cancer and neurodegeneration.
Notable Contributions
Dr. Arkin has co-founded Ambagon Therapeutics, focusing on molecular glues targeting the chaperone 14-3-3, and Elgia Therapeutics, which develops caspase inhibitors for treating chronic inflammatory diseases. She is an investigator in the UCSF Helen Diller Family Comprehensive Cancer Center, the Bakar Aging Research Institute, and the Tau Consortium. Her work has significantly advanced the field of chemical biology, particularly in addressing previously intractable drug targets.
Awards and Honors
Professor Arkin's contributions have been recognized with several prestigious awards, including:
- Arthur C. Cope Scholar Award, American Chemical Society, 2024
- Gordon Hammes Lectureship Award, American Chemical Society, 2024
- Breakthrough Chemical Biology Research Award, ONO Pharma Foundation, 2018–2021
- SLAS Innovation Award Finalist, 2013
Professional Engagements
Beyond her research, Professor Arkin is actively involved in the scientific community. She has served as Director and former President of the Academic Drug Discovery Consortium and is a Fellow and former Director of the Society for Laboratory Automation and Screening. Additionally, she contributes as an editor of the National Institutes of Health Assay Guidance Manual and serves on the editorial boards of several scientific journals.
Through her interdisciplinary approach and leadership, Professor Michelle R. Arkin continues to make significant contributions to the fields of chemical biology and drug discovery.
Peptide-Protein Complexes as Models for Protein-Protein Interactions in Drug Discovery
University of California, San Francisco
Molecular glues – compounds that induce or stabilize protein-protein interactions (PPI) – are fundamentally changing the way drug hunters think about targeting previously undruggable targets. Natural and synthetic molecular glues can induce non-native (neomorphic) interactions or further stabilize native complexes; they can also lead to pathway activation, inhibition, or even degradation of one of the target proteins. Most molecular glues have been discovered serendipitously. To capitalize on this new mechanism of action, the field requires new methods for prospective discovery of molecular glues for a particular PPI.
Our team has developed cell-active molecular glues for several proteins, including the kinase CRAF and transcription factors estrogen receptor (ER) and yes-associated protein (YAP), that bind to the phosphoprotein-chaperone 14-3-3. Our systematic approach uses disulfide tethering and other reversible covalent libraries to screen for cooperative binding with phosphopeptides derived from the intrinsically disordered regions of 14-3-3 client proteins. These peptide-protein complexes serve as reliable models for wildtype complexes and for rare diseases where the PPI has been weakened through mutations. Through screening and structure-guided optimization, we are developing the rules-of-thumb for designing molecular glues.