March 30th, 2023
Host: Katherine Donovan
Reimagining Druggability using Chemoproteomic Platforms
Dan Nomura is a Professor of Chemical Biology and Molecular Therapeutics in the Department of Chemistry and the Department of Molecular and Cell Biology in the Division of Molecular Therapeutics at the University of California, Berkeley and an Investigator at the Innovative Genomics Institute. He is also an Adjunct Professor in the Department of Pharmaceutical Chemistry at UCSF. Since 2017, he has also been the Director of the Novartis-Berkeley Translational Chemical Biology Institute focused on using chemoproteomic platforms to tackle the undruggable proteome. He is also Co-Founder of Frontier Medicines, a start-up company focused on using chemoproteomics and machine learning approaches to tackle the undruggable proteome. He is also the Founder of Vicinitas Therapeutics based on his group’s discovery of the Deubiquitinase Targeting Chimera (DUBTAC) platform for targeted protein stabilization. He is also on the Scientific Advisory Boards for Frontier Medicines, Vicinitas Therapeutics, Photys Therapeutics, Apertor Pharma, and the Mark Foundation for Cancer Research and is on the Investment Advisory Board of Droia Ventures. He earned his B.A. in Molecular and Cell Biology and Ph.D. in Molecular Toxicology at UC Berkeley with Professor John Casida and was a postdoctoral fellow at Scripps Research with Professor Benjamin F. Cravatt before returning to Berkeley as a faculty member in 2011. Among his honors include the National Cancer Institute Outstanding Investigator Award, Searle Scholar, American Cancer Society Research Scholar Award, and the Mark Foundation for Cancer Research ASPIRE award.
April 13th 2023
Host: Mikolaj Slabicki / Radosław Nowak
Template-assisted covalent modification of DCAF16 underlies activity of BRD4 molecular glue degraders
Yen-Der is a PhD student in Ben Ebert's lab at Harvard University. His research focuses on the discovery of novel molecular glues and targeted protein degradation mechanisms for cancer therapeutics. Before coming to Harvard, Yen-Der graduated from National Taiwan University with a dual degree of MD in Medicine and BS in Physics.
Michelle was born in Hong Kong and moved to the Bay Area when she was five. She graduated from University of California, Berkeley with a bachelor's degree in Molecular and Cell Biology. For her graduate studies, Michelle is interested in understanding the mechanistic principles that regulate protein homeostasis. In the Fischer lab, Michelle has worked on projects to biochemically and structurally characterize different ubiquitin ligases in the context of substrate recognition and targeted protein degradation. https://fischerlab.dana-farber.org/
Muhammad Murtaza Hassan
Murtaza, born in Pakistan, and raised in Canada where he conducted his university studies (HBSc, University of Toronto 2009-2013; MSc, York University 2014-2017, Supervisor: Edward Lee-Ruff; PhD, University of Toronto 2017-2021, Supervisor: Patrick T. Gunning) is an avid chemical biology enthusiast.
For his doctoral studies at the Gunning lab, Murtaza developed some of the most potent and selective HDAC8 inhibitors in literature, using conformationally constrained benzamides to complement the unique HDAC8 pocket.
Currently, his postdoctoral work with Professor Nathanael Gray at Stanford focuses on expanding current pharmacological tools to target the undruggable proteome. One example of this involves exploring the potential for trans-labelling molecules. Based on the JQ1 scaffold, Murtaza developed MMH1 and MMH2, that bind BRD4 non-covalently, but covalently trans-label DCAF16 (an E3 ligase), leading to the targeted degradation of BRD4. These monovalent trans-labelling molecules demonstrate nanomolar BRD4 degradation, on-par with well-established bivalent degraders such as MZ1 and dBET6.
An intramolecular bivalent degrader glues an intrinsic BRD4-DCAF16 interaction.
University of Dundee
Oliver did his PhD at the University of Glasgow under the supervision of Dr Thimo Kurz, characterizing the role of the NEDD8 E3 ligase DCNL5 in the apoptosis pathway. Continuing his research in the protein homeostasis field, Oliver moved to the University of Dundee in May of 2020 to begin working as a postdoctoral cell biologist on the collaborative project between the Ciulli group and Eisai Co., Ltd., developing and validating new molecular glues and PROTACs. Here, he has continued to broaden his skills in molecular biology and biochemistry and chemical biology.
Matthias did his PhD in Johannes Zuber’s lab at the Institute of Molecular Pathology Vienna, where he established temporally resolved CRISPR screens that led to the discovery of AKIRIN2 as the central component in the metazoan nuclear proteasome import pathway. In his work in the Winter lab, he is now looking to combine his interests in genetic screening and proteasome biology to elucidate the genetic determinants underlying chemically induced targeted protein degradation.
University of Dundee
Angus Cowan obtained his PhD in 2017 at the Walter and Eliza Hall Institute (Melbourne) under the supervision of Professors Peter Czabotar and Peter Colman, investigating the structure and function of pro-apoptotic BCL-2 family proteins. After a 2 year postdoc under Professor Czabotar working as part of a team collaborating with an industry partner to develop modulators of necroptosis, he joined the group of Professor Alessio Ciulli at the University of Dundee (Scotland) in January 2020. Supported by a Marie Skłodowska-Curie Fellowship, Angus’ research focuses on structural and functional investigation of substrate receptors of CRL4 E3 ligases, with a view to exploiting them for targeted protein degradation with PROTACs and molecular glues
April 27th, 2023
Host: Hojong Yoon
May 11th 2023
Host: Mikolaj Slabicki
Boston Children’s Hospital
Lessons from dTAG-mediated acute depletion of the "undruggable" transcription factor BCL11A
Stuti Mehta is a Scientist at the Boston Children’s Hospital, and an Instructor at the Harvard Medical School. Stuti studied biochemistry and biotechnology at St. Xavier’s college in India, before moving on to obtain an MSc and DPhil (PhD) working on epigenetic mechanisms of gene expression control at the Medical Research Council at Oxford University, UK. Stuti is broadly interested in understanding finer mechanistic details of gene expression control by transcription factors and epigenetic proteins, most recently by deploying targeted protein degradation approaches. At the BCH, she works with Stuart Orkin to use Targeted protein degradation strategies to deplete the repressive Zn-transcription factor BCL11A in service of inducing the curative fetal form of hemoglobin in b-hemoglobin disorders. Here, she also leads a large-scale screening effort to identify from diverse sources, glue-like chemicals that lead to the depletion of, or interference with the repressive function of BCL11A.
Matthew F. Calabrese
A covalent BTK ternary complex compatible with targeted protein degradation
Matt Calabrese obtained his PhD in Molecular Biophysics and Biochemistry from Yale University where he studied protein folding in the lab of Dr. Andrew Miranker. He then moved on to a postdoctoral fellowship with Dr. Brenda Schulman at St. Jude Children’s Research Hospital where he studied the structure and function of the ubiquitin proteasome system, with a focus on cullin-RING E3 ligases. In 2011, Matt joined Pfizer as a Senior Scientist in structural biology, and at present, he is Senior Director and Head of the Structural and Molecular Sciences department.