Katherine Donovan, Dana-Farber Cancer Institute

Katherine Donovan, Dana-Farber Cancer Institute

Location: 
Online
Start Time: 
Mon 19/04/2021 - 10:00 AM
End Time: 
Mon 19/04/2021 - 11:00 AM

WEHI Special lecture hosted by Professor David Komander

Katherine Donovan
Senior Scientist, Fischer Laboratory - Structural Biology, Dana-Farber Cancer Institute

Targeted Protein Degradation: Mapping the Degradable Proteome
 

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Including Q&A session
 

Frequently used to treat morning sickness in the 1950’s, thalidomide led to the birth of thousands of children with severe birth defects. Despite their teratogenicity, thalidomide and related IMiD drugs are currently a mainstay of cancer treatment and now, decades later, we are starting to understand their therapeutic mechanism of action – they are small molecule inducers of ubiquitin-mediated protein degradation. Here, I will describe how we mapped novel zinc-finger transcription factor targets of IMiDs and identified SALL4 as the target likely responsible for the devastating birth defects caused by these drugs. In addition to their use as a highly effective multiple myeloma treatment, over the last 5yrs, IMiDs have proven valuable as ligase recruiters in the new therapeutic modality – PROTACs. Here, I will describe how we designed, synthesized and profiled a library of heterobifunctional kinase degraders to map the degradation of over 200 kinases and used this library to explore important aspects of degrader design.

Katherine Donovan is a Senior Scientist in the Fischer Lab where she works on methods of hijacking the ubiquitin proteome system for the development of molecular glues and PROTACs for targeted protein degradation. She completed her PhD training in protein biochemistry and structural biology at the University of Canterbury, New Zealand. After joining the Fischer Lab as a Postdoc she developed an interest in proteomics as a specialized technology for quantifying protein-level expression changes in response to various perturbations. Katherine set up and optimized a robust proteomics pipeline in the Fischer Lab as well as in the Center for Protein Degradation during her time as the Proteomics Group Lead. She has used this proteomics technology to identify the degradation targets of many molecules including the identification of SALL4 as the target of thalidomide and more recently, she co-led the effort to map the degradable kinome. Katherine continues to work on several projects related to ligase biology and protein degradation and also leads the proteomics operation in the Fischer Lab.