SC6: Targeted Protein Degradation Using PROTACs and Molecular Glues
MONDAY, JUNE 17 | 5:30-8:30pm (DINNER PROVIDED)
ABOUT THIS COURSE:
Targeted protein degradation using molecular glues and bifunctional small molecules known as proteolysis-targeting chimeric molecules (PROTACs) are emerging as a useful tool for drug discovery, and as a new therapeutic modality for chasing previously
“undruggable” targets. This course will cover the basic understanding of what these entities are, how they work and how they can be applied to target and degrade specific proteins of interest. Case studies drawn from the work that the
instructors have done in their labs will also be presented.
WHAT YOU WILL LEARN:
- Pros and cons of using PROTACs versus Molecular Glues
- PROTACs and molecular glues, do we use them to induce protein degradation only?
- Which binding site on E3 ligase should be targeted by PROTACS/Glues for the efficient substrate recruitment?
- Molecular events required for PROTAC mediated degradation (ternary complex, availability of lysines, orientation of E3s, and more)
- New screening technologies available to discover PROTAC and molecular glues for E3 ligases
Eric Fischer, PhD, Assistant Professor, Cancer Biology, Dana-Farber Cancer Institute/Harvard Medical School
After studying biology at the University of Basel in Switzerland, Eric Fischer obtained his PhD at the Friedrich Miescher Institute for Biomedical Research where he conducted pioneering work on the structure, function and mechanism of action of thalidomide
and its efficacy target Cereblon. After his PhD he moved to the Dana-Farber Cancer Institute to start his lab in the vibrant chemical biology community in Boston. He is also an Assistant Professor of Biological Chemistry and Molecular Pharmacology
at Harvard Medical School. Dr. Fischer has been recognized for his pioneering work on the structure of cereblon and the mechanism of action of thalidomide and has significantly contributed to our understanding of small molecule mediated protein degradation.
His lab studies the structure and function of ubiquitin E3 ligases and translates these insights into the development of novel therapeutic strategies.
Davide Gianni, PhD,
Associate Director, Discovery Sciences, AstraZeneca
Davide Gianni currently leads the Cellular Assay Development team in Discovery Sciences (AZ) in Cambridge UK. The main focus of the team is to deliver the cellular assay portfolio for key therapeutic areas for AZ. He joined AZ in August 2015 from Boehringer-Ingelheim
(Vienna) where he was in charge of leading a team of scientists to identify and validate drug target for oncology drug discovery. Davide got his PhD from University of Naples (Italy) and completed his postdoctoral studies at The Scripps Research Institute
(TSRI) in La Jolla before relocating to Europe. He has authored >20 peer-reviewed publications and review articles in high impact journals covering several scientific areas including cancer and molecular biology, neurodegeneration and drug discovery.
PhD, Scientist/Project Lead, Jnana Therapeutics; Formerly at Laboratory of Drs. James Bradner/Nathanael Gray, Harvard Medical School
During her undergraduate years at Wellesley College, Lara worked as a research assistant in the lab of Matthew Meyerson (Broad Institute of Harvard and MIT) where she conducted research on the characterization of the potency, activity, and functional
effects of a novel cytotoxic agent. Lara completed a PhD candidate in Biomedical and Biological Sciences and Therapeutics at Harvard Medical School. She conducted her graduate research in the labs of Dr. Jay Bradner and Dr. Nathanael Gray where
she focused on targeted degradation as an approach to developing novel epigenetic cancer therapeutics. Lara is currently a biochemist at Jnana Therapeutics, a biotech company dedicated to launching solute carrier transporters to the forefront