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Previous Speakers (2022 part 2)

Some seminars were recorded and accessible for a limited time on our youtube channel.

September 1st, 2022  - 4:00 PM EST

Host: Mikołaj Słabicki / Katherine Donovan

Time Change:

4 PM (EDT) / 1 PM (PT) , 
9 pm (BST), 10 pm (CEST) 

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Benjamin L. Ebert, MD, PhD

Dana-Farber Cancer Institute

 
 

Targeted protein degradation for the treatment of cancer

Dr. Benjamin Ebert is the Chair of Medical Oncology at the Dana-Farber Cancer Institute, the George P. Canellos, MD and Jean S. Canellos Professor of Medicine at Harvard Medical School, a Howard Hughes Medical Institute Investigator, and an Institute Member of the Broad Institute.

 

The Ebert laboratory focuses on the molecular basis and treatment of hematologic malignancies and its non-malignant precursor conditions, with a particular focus on myelodysplastic syndromes (MDS) and clonal hematopoiesis.  The Ebert laboratory demonstrated that lenalidomide, a derivative of thalidomide, binds the CRL4-CRBN E3 ubiquitin ligase and induces degradation of specific substrates.  Subsequent research has examined novel mechanisms of drug-induced protein degradation that expand the spectrum of protein substrates that can be targeted pharmacologically.

 

Dr. Ebert is an elected member of the National Academy of Medicine, the American Society for Clinical Investigation and the Association of American Physicians.  He served as President of the American Society for Clinical Investigation in 2017.  He received the William Dameshek Prize from the American Society of Hematology in 2017, the Meyenburg Prize for Cancer Research in 2019, the Sjöberg Prize from the Royal Swedish Academy of Sciences in 2021, and the Korsmeyer Award from the American Society for Clinical Investigation in 2021.

 

Dr. Ebert received a bachelor's degree from Williams College and a doctorate from Oxford University as a Rhodes Scholar in the laboratory of Sir Peter Ratcliffe.  He completed an M.D. from Harvard Medical School, a residency in internal medicine at Massachusetts General Hospital, and a fellowship in hematology/oncology at the Dana-Farber Cancer Institute.

This event will be held on-site and broadcast virtually via Zoom.
A reception will be held on-site after the talk from 5:10- 7:30 PM (EDT).

Event Location:  

Linda K. Paresky Conference Center, Simmons University 300 Fenway Boston, MA 02115

There is a limited number of registration slots available and is based on the seminar room capacity. Registration will work on a first come first served basis. Registration is free of charge, but please cancel your registration (drop line to DFCI.TPD@gmail.com) if you cannot join to allow space for others.

Sponsored by:

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Chemical biology studies of the thalidomide binding domain of cereblon

Abstract: The E3 ligase adaptor cereblon is a target of thalidomide and lenalidomide, therapeutic agents that are used in the treatment of hematopoietic cancers despite teratogenic toxicity.  These agents act in part by modulating substrate selection and degradation through the thalidomide binding domain of cereblon.  However, despite the expanding use of cereblon in targeted protein degradation technologies, identification of a degron, the recognition domain that controls the endogenous substrate selection mechanisms of cereblon, has remained elusive. Here, I will describe chemoproteomics approaches to target identification in the study of molecular glues like lenalidomide, and how these chemical biology approaches can reveal new insights about the thalidomide binding domain of cereblon.

Biosketch: Christina M. Woo is an Associate Professor in the Department of Chemistry and Chemical Biology at Harvard University, and an affiliate member of the Broad Institute.  Christina’s research focuses on the design of small molecule and protein approaches to alter post-translational modifications and the signaling outcomes they produce. She obtained a BA in Chemistry from Wellesley College (2008) and conducted undergraduate research with Professor Dora Carrico-Moniz.  She obtained her PhD in 2013 from Yale University under the guidance of Professor Seth B. Herzon as an NSF predoctoral fellow in the synthetic and chemical biology studies of diazofluorene antitumor antibiotics.  In 2013, Christina joined the laboratory of Professor Carolyn R. Bertozzi at the University of California Berkeley as a Jane Coffins Child postdoctoral fellow and continued at Stanford University (2015) as a Burroughs Wellcome Fund postdoctoral fellow, where she developed a mass-independent chemical glycoproteomics platform for the identification of non-templated post-translational modifications.  Christina joined the faculty at Harvard University in 2016.  Her research has been recognized by the Camille-Dreyfus Teacher-Scholar Award, Sloan Research Foundation, NSF CAREER, Bayer Early Excellence in Science Award, the NIH DP1 Avenir Award, and the Ono Pharma Foundation Breakthrough Science Award.

Link to the recorded seminar: https://youtu.be/KMABGEAnV_M

September 29th, 2022  
Host: Breanna Zerfas

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Using cryoEM to see molecular glues in action

Gabe Lander
Scripps Research

Gabe is a Professor in the Department of Structural and Computational Biology at Scripps Research. His group’s research is focused on combining cryo-EM methodologies with biochemical, biophysical, and computational techniques to produce detailed mechanistic descriptions of the molecular processes that underlie cellular homeostasis and stress-response pathways. Gabe’s studies challenge existing paradigms, with a notable track record of overturning existing long-standing myths in both cryo-EM as well as biology. The pioneering methodological avenues of research established by Gabe’s group have enabled detailed examination of molecular assemblies ranging widely in size and shape to understand their architectures, the conformational landscapes that are responsible for molecular function, and how these landscapes are influenced by small molecule ligands. These research strategies are being used to explore and define the molecular bases of human disease, including heart disease and cancers. Gabe received a B.S. in biochemistry and computer science from Binghamton University, and subsequently carried out his graduate studies at Scripps Research under the joint supervision of Bridget Carragher, Clint Potter, and Jack Johnson. Gabe performed his postdoctoral work in the lab of Eva Nogales at UC Berkeley, where he collaborated closely with Drs. Andreas Martin and Jennifer Doudna. He joined Scripps as an Assistant Professor in 2013. Over his academic career, Gabe has received numerous recognitions and awards, which include the Damon Runyon Dale F. Frey award, an NIH Innovator Award, Searle and Pew Scholarships, an Amgen Young Investigator Award, and a Protein Science Young Investigator from the Protein Society.

Link to the recorded seminar: https://youtu.be/L13X8_jqtP8

October 13th, 2022  

Host: Radek Nowak

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James Duncan
Fox Chase Cancer Center
Exploring the drug efflux pump MDR1 in PROTAC resistance

James Duncan, Ph.D., is an Associate Professor at Fox Chase Cancer Center in the Cancer Signaling and Epigenetics Program.  He received both of his undergraduate and graduate degrees in Biochemistry from the University of Western Ontario and carried out his postdoctoral studies at the University of North Carolina.  The Duncan lab specializes in functional proteomics and cell signaling pathways, studying the role of protein kinases in the development of cancer and drug resistance. He has been applying mass spectrometry-based approaches including shotgun proteomics, phosphoproteomics and kinomics to study cancer signaling for nearly 20 years. The Duncan lab’s proteomics studies have defined mechanisms of drug action and resistance to a variety of molecular targeted agents, including PROTACs.

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Holly Soutter, Wei Jiang
Broad Institute of MIT and Harvard
A biophysical toolkit for characterization of bifunctional molecules that induce ternary complex formation.

Holly Soutter is Director of Biochemistry and Biophysics within the Center for the Development of Therapeutics (CDoT) at the Broad Institute of MIT and Harvard. Her research unit supports projects across multiple therapeutic areas to identify, validate, and mechanistically characterize potential small molecule therapeutics. Her team has expertise and capabilities in multiple techniques including SPR, NMR, mass spectrometry, enzymology, and many others.  Dr. Soutter has more than 15 years of experience in drug discovery and development in large pharma and biotech. She is co-inventor of multiple clinical candidates, and has co-authored more than 20 scientific publications. She received her B.A. in chemistry from Hunter College, and her M.A. and Ph.D. in chemistry from Clark University.

Wei Jiang is a Senior Research Scientist in the Biochemistry and Biophysics group within the Center for the Development of Therapeutics (CDoT) at the Broad Institute of MIT and Harvard. Dr. Jiang has been at the Broad for nearly a decade working on therapeutics projects across the CDoT portfolio, developing and executing a great number of protein-based biochemical and biophysical assays for drug development.  In 2019, she was recognized with a Broad Excellence Award in Extraordinary Work Related to the COVID-19 Pandemic for her contributions to rapidly establishing the Broad’s COVID testing capabilities.  She received her B.S. in Biochemistry from Nanjing University and her Ph.D. in Biochemistry and Molecular Biology from Penn State University.

Link to the recorded seminar: https://youtu.be/EXbroBu-EIw

October 27th, 2022  

Host: Hojong Yoon

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Lindsey James
University of North Carolina
Altering the H3 methylation landscape through degradation of methyl-lysine reader proteins

Lindsey James is an Assistant Professor in the Division of Chemical Biology and Medicinal Chemistry in the Eshelman School of Pharmacy at the University of North Carolina. The James laboratory integrates expertise in organic chemistry, medicinal chemistry, chemical biology, and chromatin biology in order to discover novel epigenetic inhibitors, while applying these inhibitors to develop an improved understanding of chromatin regulation and better define the role of epigenetic proteins in disease. She is also the Director of Chemical Biology within the Center for Integrative Chemical Biology and Drug Discovery (CICBDD) where she collaborates closely with UNC faculty to provide medicinal chemistry and chemical biology expertise to bear on biological targets of therapeutic relevance. She obtained a B.A. in chemistry from Colgate University and a PhD in bioorganic chemistry from the University of North Carolina under the guidance of Professor Marcey Waters. She was a postdoctoral fellow in Stephen Frye’s group at the University of North Carolina and joined the faculty of the University of North Carolina as an Assistant Professor in 2019.

Link to the recorded seminar: https://youtu.be/MAfXODlYDS0

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Michael Erb
Scripps Research Institute
Therapeutic opportunities revealed by and for targeted protein degradation.

Michael Erb is an Assistant Professor in the Department of Chemistry at The Scripps Research Institute. He received his PhD from Harvard University under the mentorship of Dr. James Bradner and was then recruited to TSRI in October 2017 to lead an independent group as one of the inaugural Scripps Fellows. Dr. Erb is the recipient of an NIH Director’s Early Independence Award (2018) and an Ono Pharma Foundation Breakthrough Science Initiative Award (2020) and was promoted to Assistant Professor in July 2020. His laboratory is principally interested in modulating tumorigenic gene regulatory programs with pharmacological tools.

Link to the recorded seminar: https://youtu.be/yKfol2oqxoI

November 10th, 2022

Host: Breanna Zerfas

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Alex Hanzl

Center for Molecular Medicine in Vienna

Scalable E3-specific degrader discovery by dynamic tracing of substrate receptor abundance

Alexander Hanzl is a PhD student in the laboratory of Georg Winter at the Center for Molecular Medicine in Vienna. Initially his work revolved around understanding resistance mechanisms in targeted protein degradation by employing deep mutational scanning strategies. Subsequently, Alex developed phenotypic screening approaches to identify novel E3 ligases amendable to this therapeutic paradigm. Prior to joining CeMM in 2017, Alex obtained his MSc focusing on epigenetics at the FMI in Basel. He originally trained as an organic chemist for his BSc degree and moved into chemical biology after.

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Anthony Slavin
Kymera Therapeutics
Identification of Highly Potent and Selective Interleukin-1 Receptor Associated Kinase 4 (IRAK4) Degraders for the Treatment of Autoimmune Disease

As Vice President, Immunology at Kymera Therapeutics, Anthony leads the Immunology team at Kymera Therapeutics and brings deep research and development experience in both small molecule and biologic drug discovery. He has been involved in multiple aspects of drug discovery and development in pharmaceutical and biotechnology companies in the U.S. for more than 20 years, leading discovery, and pharmacology teams, as well as being involved in efforts focused on the external identification and diligence of novel technologies and assets suitable for in-licensing and/or acquisition. Prior to joining Kymera, Anthony held leadership positions in Immunology at Abbvie and Boehringer Ingelheim, where he oversaw research departments dedicated to identifying and developing therapeutics for grievous autoimmune diseases, including the recently approved SKYRIZI, a monoclonal antibody targeting IL-23. He started his career at Tularik which was acquired by Amgen, and was a group leader at the Genomics Institute of the Novartis Research Foundation (GNF). Anthony holds a BSc (Hons.) and a PhD degree from the University of Melbourne and trained as a research fellow at Harvard Medical School and Stanford University.

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November 17th, 2022  

Host: Hojong Yoon

Mikko Taipale

University of Toronto

Proteome-scale discovery of proximity-dependent degraders and stabilizers

Mikko Taipale is an Associate Professor in the Department of Molecular Genetics at the Donnelly Centre at the University of Toronto. He received his MSc in genetics at the University of Oulu, Finland (close to the arctic circle). He then joined the international PhD programme in EMBL in Heidelberg, Germany. He completed his PhD in Asifa Akhtar’s lab, working on chromatin regulation by histone acetylation. He then joined Sue Lindquist’s lab at the Whitehead Institute for postdoctoral training. There, he focused on the client recognition mechanisms of Hsp90 chaperone and co-chaperones and on developing high-throughput protein/protein and drug/target interactions. Mikko started his lab at the Donnelly Centre and the University of Toronto in 2014. Now, Taipale lab is focused on diverse aspects of functional proteomics and genomics, including protein homeostasis, transcriptional regulation, disease variant phenotyping, and host/pathogen interactions.

Link to the recorded seminar: https://youtu.be/weL6Wh01ViQ

December 1st, 2022
Host: Radoslaw Nowak

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Lorraine Glennie & Luke Simpson

University of Dundee

Target protein localization and its impact on PROTAC-mediated degradation

Lorraine is a PhD student in the Sapkota Lab of the MRC PPU, University of Dundee. Her PhD work branches into two main areas: (1) investigating the impact of cellular factors on PROTAC-mediated degradation and (2) exploring how the elusive FAM83 proteins control cellular function via their interaction with casein kinase 1 (CK1). Prior to her PhD study, she obtained a BSc (Hons) in Molecular Biology at the University of Edinburgh before completing an MRes in Biomedical Sciences at the University of Glasgow, focusing on the regulation of inflammatory signalling by post-translational modifications. 

Luke completed his PhD under the supervision of Prof Gopal Sapkota and Dr Ian Ganley in the MRC Protein Phosphorylation and Ubiquitylation (PPU) Unit at the University of Dundee, Scotland. Luke’s doctoral research centred around exploring technologies for targeted protein modification and involved the combined use of nanobody- and PROTAC-based technologies for targeted protein degradation. Since obtaining his PhD, Luke joined Prof Alessio Ciulli’s Group in the Centre for Targeted Protein Degradation (CeTPD) at the University of Dundee as a Cell Biologist as part of the PROTAC Drug Discovery collaboration with Boehringer Ingelheim.

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Sarath Ramachandran
University of Dundee
Structure-based design of a phosphotyrosine-masked covalent ligand targeting the E3 ligase SOCS2 

I joined CeTPD-Boehringer-Ingelheim (ACBI) collaboration team as a senior drug discovery scientist (structural biology/biophysics) in March 2022 and am currently working on tackling challenging cancer targets using targeted protein degradation. Prior to joining the ACBI team, I was leading the EUbOPEN collaboration from Alessio’s lab and was involved with developing chemical probes targeting novel E3 ligases and expanding the current arsenal of E3 ligase recruiting PROTAC handles. I joined Alessio’s lab in 2017 after I completed my Ph.D. under the supervision of Prof. Sivaraman Jayaraman at the National University of Singapore, where I worked on understanding the allosteric inhibition mechanism of a key cancer target - glutaminase. I did my Master’s in Biotechnology from IIT-Guwahati, and bachelor's in Biotechnology from VTU, Karnataka (India).

December 15th, 2022

Host: Katherine Donovan

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Miklós Békés

Arvinas

The Arvinas PROTAC® Discovery Engine: 
Insights from Discovering & Developing Molecules That Induce Targeted Protein Degradation

Miklós is Associate Director of Platform Biology at Arvinas, leading the Degrader Mechanisms Group tasked with aiding in the discovery and characterization of novel small molecule PROTAC® protein degraders in the expanding TPD landscape, where his group is responsible for early discovery (biochemistry, structural biology, biophysics and cell biology). Prior to Arvinas, Miklós worked at Nurix Therapeutics, and conducted his post-doctoral studies in the ubiquitin space in New York City at New York University and at Memorial Sloan Kettering Cancer Center. Miklós earned his Ph.D. in Molecular Pathology from the University of California, San Diego conducting studies on ubiquitin’s cousin, SUMO, at the Burnham Institute in La Jolla. A lifelong scientific fan of #ubiquitin, he is passionate about using our mechanistic understanding of a cell's degrader machinery to advance small molecule drug discovery and development in targeted protein degradation with the ultimate goal of potentially delivering benefit to patients. 

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