September 12th, 2024
2024 DFCI-TPD In Person Meeting
12.00-12.30 pm Arrival, Registration and Boxed lunch
12:30 -12:40 pm Welcome Remarks
Dana-Farber Targeted Protein Degradation Organizing Committee Mikołaj Słabicki, Katherine Donovan
12:40 -1:40 pm Keynote: Eric Fischer, DFCI, host: Katherine Donovan
Molecular Mechanisms of Ubiquitin Ligases. From Structure to Therapies
1:40 - 2:10 pm Mikołaj Słabicki, MGH/DFCI/Broad Institute, host: Hojong Yoon
Expanding the human zinc finger degrome targeted by glutarimide analogs through CRBN
2:10 - 2:40 pm Samantha Bevill, DFCI, host: Breanna Zerfas
Tumor-specific PROTACs that exploit amplification of the MDM2 E3 ubiquitin ligase
2:40 – 3:15 pm Light snack / Coffee break
3:15 – 3:45 pm Pamela Ting, Novartis, host: Zuzanna Kozicka
A molecular glue degrader of the WIZ transcription factor for fetal hemoglobin induction
3:45 – 4:15 pm Liron Bar-Peled, MGH, host: Samuel Ojeda
An Omics Approach to Drug Discovery
4:15 – 5:30 pm Panel Discussion, Moderator: Breanna Zerfas
Samantha Nelson, Scientific Editor, Cell Chemical Biology
Sheryl Gough, Associate Director of Oncology Discovery, Arvinas
Chris Bahl, President/CSO/Co-founder, AI Proteins
5:30 – 8:00 pm Reception (Appetizers and Open Bar)
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.
Event organized by:
Dana-Farber Targeted Protein Degradation Organizing Committee
Mikolaj Slabicki, Katherine Donovan, Hojong Yoon, Breanna Zerfas, Zuzanna Kozicka, Samuel Ojeda
Sponsored by:
Speakers:
Eric Fischer
DFCI
Molecular Mechanisms of Ubiquitin Ligases. From Structure to Therapies
Eric Fischer, Ph.D. is the Director of the Chemical Biology Program at Dana-Farber Cancer Institute, Professor of Biological Chemistry and Molecular Pharmacology at Harvard Medical School, Director of the DFCI Center for Protein Degradation, and Co-Director of the Center for Therapeutics Discovery. Dr. Fischer trained in structural biology and biochemistry at the University of Basel and conducted his doctorate studies at the Friedrich Miescher Institute for Biomedical Research. His lab at Dana-Farber focusses on the understanding of fundamental processes in ubiquitin signaling, and the molecular basis of ubiquitin ligase activity, targeting and regulation. His lab seeks to leverage this understanding for the development of novel therapeutic approaches, such as targeted protein degradation. He and his lab have significantly contributed to our understanding of small molecule mediated protein degradation, and its widespread application in academia and industry.
Mikołaj Słabicki
MGH/DFCI/Broad Institute
Expanding the human zinc finger degrome targeted by glutarimide analogs through CRBN
Mikołaj Słabicki earned his Ph.D. at the Max Planck Institute of Molecular Cell Biology and Genetics in Dresden, Germany. Dr. Słabicki then conducted his post-doctoral research as a Marie Skłodowska Curie Scholar in Dr. Benjamin Ebert’s laboratory at the Dana-Farber Cancer Institute and in Stefan Fröhling’s laboratory at the German Cancer Research Center in Heidelberg, Germany. Mikołaj Słabicki later became a Group Leader in the Cancer Program at the Broad Institute, a member of Dr. Benjamin Ebert’s Laboratory, and a Senior Staff Scientist at the Dana-Farber Cancer Institute. In the summer of 2024, Mikołaj began a faculty position at the Massachusetts General Hospital (MGH) Cancer Center. His laboratory aims to expand the druggable proteome by employing functional genomics, high-throughput screening, chemical biology, cell biology, and biochemical techniques to identify and characterize new molecular glue degraders and novel mechanisms of targeted protein degradation.
Samantha Bevill
DFCI
Tumor-specific PROTACs that exploit amplification of the MDM2 E3 ubiquitin ligase.
Samantha Bevill, PhD is a research fellow in the Bernstein and Qi labs at the Dana-Farber Cancer Institute. Her research interests are rooted in understanding fundamental mechanisms of tumor biology that can be leveraged to design selective cancer therapeutics. She received her B.S. in Biology from Clemson University in 2012 and her Ph.D. in Pharmacology from the University of North Carolina at Chapel Hill in 2018. Her doctoral work in Dr. Gary Johnson’s lab used proteomic techniques to identify compensatory signaling pathways responsible for adaptive resistance to targeted kinase inhibitor therapies in breast cancer. As a post-doctoral fellow in Dr. Bradley Bernstein’s laboratory, she led a large project that sought to define the transcriptional regulatory landscape of liposarcoma. Her work defined a novel P53-independent role for MDM2 occupancy across the genome. This work defines supraphysiologic MDM2 as having a novel role in highly amplified tumors and revealed MDM2 high cells mediate therapeutic resistance. Concurrent to this work, she has collaborated closely with the lab of Jun Qi to establish new therapeutic strategies for selective targeting of highly MDM2-amplified tumor subpopulations using PROTAC degraders.
Pamela Ting
Novartis
A molecular glue degrader of the WIZ transcription factor for fetal hemoglobin induction.
Pam is an Associate Director at Novartis Biomedical Research where she leads internal and external collaboration teams to develop therapies for classical hematology and hematologic malignancies. Pam has broad expertise in drug development from target discovery to IND and experience across multiple innovative platforms including degraders, cell and gene therapy. She received her B.A. in Molecular & Cellular Biology from University of California, Berkeley, her Ph.D. in Biological Chemistry from University of California, Los Angeles, studying the regulation of BCR-ABL in chronic myelogenous leukemia, and studied allogeneic hematopoietic stem cell transplantation as a postdoctoral fellow at the Genomics Institute of the Novartis Research Foundation.
Liron Bar-Peled
MGH
An Omics Approach to Drug Discovery
Liron received his Bachelor of Science degree in Biochemistry from the University of Georgia in 2004. Liron received his PhD in Biology from the Massachusetts Institute of Technology, where he used advanced cellular and molecular techniques to uncover how nutrients are sensed by the mTORC1 pathway in the laboratory of David Sabatini. In 2013 as a Damon Runyon Postdoctoral fellow, he joined the laboratory of Ben Cravatt at the Scripps Research Institute to understand how cancer cells respond to oxidative stress. Employing chemical, proteomic and biochemical approaches, Liron revealed new druggable components of the NRF2 antioxidant response pathway uncovering new mechanisms by which NRF2 regulates metabolic pathways. In early 2019, Liron joined the Center for Cancer Research at the Massachusetts General Hospital and the Department of Medicine at Harvard Medical School. He is currently an Associate Professor of Medicine in Biological and Biomedical Sciences.
Panelists:
Samantha Nelson
Scientific Editor, Cell Chemical Biology
Samantha originates from central Florida, where she grew up and earned her bachelor's and master's degrees. She then relocated to Massachusetts to pursue her PhD in Immunology and Microbiology at UMass Chan Medical School. During her doctoral studies, Samantha delved into metabolism, metal biology, antibiotic development, and genetic engineering techniques in Mycobacterium tuberculosis. After completing her PhD, she joined Cell Chemical Biology as a scientific editor. Although her academic background is rooted in microbiology, Samantha is endlessly curious about all facets of biology and is passionate about facilitating the dissemination of scientific research. In her leisure time, she channels her curiosity into identifying native animal and plant species, exploring historical costuming techniques, and learning to lindy hop.
Sheryl Gough
Associate Director of Oncology Discovery, Arvinas
Sheryl Gough is currently an Associate Director in the Oncology/Biology team at Arvinas Operations, Inc., New Haven, Connecticut. Sheryl has contributed to multiple PROTAC programs at Arvinas over the past nine years, including leading studies for the preclinical in-vivo pharmacology of Vepdegestrant (ARV-471, an estrogen receptor (ER) degrading PROTAC) for the treatment of ER+ breast cancer, and is the biology lead for ARV-393, a BCL6 PROTAC recently progressed to Phase I trials for non-Hodgkin lymphoma. Prior to Arvinas, Sheryl was a Visiting Post-Doctoral Fellow at the NCI/NIH with Dr Peter Aplan for six years working on murine models of hematological malignancies and NUP98-gene fusions. Sheryl received her PhD in cancer genetics in 2003 from the University of Otago, New Zealand, where her work focused on characterizing chromosome translocations and gene mapping in leukemia patients under the mentorship of Dr Christine Morris at the Christchurch School of Medicine, University of Otago.
Chris Bahl
President/CSO/Co-founder, AI Proteins
Christopher D. Bahl, MS, PhD is a protein designer, biochemist, structural biologist and entrepreneur. Chris pioneered the ability to computationally design miniproteins de novo as a postdoctoral fellow with David Baker at the Institute for Protein Design in Seattle. In 2017, Chris joined the Institute for Protein Innovation in Boston as one of the founding faculty members, with co-appointments at Boston Children's Hospital and Harvard Medical School. In 2021, Chris and members of his laboratory left academia together to found AI Proteins, Inc., where Chris currently serves as the President and Chief Scientific Officer. AI Proteins is leveraging the power of miniproteins to rapidly create novel therapeutics de novo, a game-changing approach with the potential to transform the pharmaceutical industry.
September 26th, 2024
Host: Hojong Yoon
Gopal Sapkota
University of Dundee
Targeted dephosphorylation of phospho-proteins through induced-proximity
Gopal is originally from Nepal but obtained a Masters degree in Biochemistry from the University of Bath in 1999. Gopal received his Ph.D. from the University of Dundee in 2003 and then joined Joan Massagué’s laboratory at Memorial Sloan-Kettering Cancer Center in New York, to undertake postdoctoral research to study the TGFβ pathway regulation, for which he received the prestigious Damon Runyon Cancer Research Fellowship. Gopal returned to Dundee in November 2008 to start his group at the MRC PPU, and in 2014 became a tenured Programme Leader.
Lab research: https://sites.dundee.ac.uk/sapkota-lab/
October 10th, 2024
Host: Breanna Zerfas / Katherine Donovan
Cheryl Arrowsmith
University of Toronto
Recruitment of FBX022 for Target Degradation.
Cheryl Arrowsmith is a Senior Scientist at the Princess Margaret Cancer Centre, Professor in the Department of Medical Biophysics, University of Toronto, and the Chief Scientist of the Structural Genomics Consortium (SGC) at the University of Toronto. Her research focuses on the structural and chemical biology of chromatin and epigenetic regulatory factors especially as relates to cancer and drug discovery. In partnership with major pharmaceutical companies, she leads the SGC’s international open science program that is developing and distributing unencumbered Chemical Probes that support the
discovery of new medicines. She received her Ph.D. from the University of Toronto and carried out postdoctoral research at Stanford University, and was co-founder of Affinium Pharmaceuticals, which developed a new medicine for multidrug resistant bacteria. She has published over 300 research articles, and was recognized by Clarivate Analytics as being among the worlds top 1% of highly cited scientists in 2018, 2019, 2021, 2022. She was elected an AAAS Fellow (2015), and a Fellow of the Royal Society of Canada (2020).
Xiaoyu Zhang
Northwestern University
A CRISPR activation screen identifies FBXO22 supporting targeted protein degradation
Xiaoyu Zhang received his B.S. and M.S. degrees at Zhejiang University. He obtained his Ph.D. degree in Biochemistry and Chemical Biology from Cornell University, where he studied with Professor Hening Lin and demonstrated lysine fatty-acylation as an abundant and physiologically relevant protein posttranslational modification. As a Damon Runyon fellow at The Scripps Research Institute, he conducted his postdoctoral research with Professor Benjamin Cravatt and developed a proteomic platform to discover novel E3 ligases that support targeted protein degradation. In 2022, Xiaoyu started his independent career as an assistant professor at Northwestern University. His research group integrates chemical proteomics, functional genomics and chemical genetics to discover small molecules that modulate protein functions through novel mechanisms.
October 24th, 2024
Host: Zuzanna Kozicka
Derek Bartlett
University of North Carolina
PK-PD modeling for targeted protein degradation
Derek Bartlett is an assistant professor in the Division of Pharmacotherapy and Experimental Therapeutics within the UNC Eshelman School of Pharmacy at the University of North Carolina at Chapel Hill. He received a BS degree in chemical engineering from Stanford University and MS and PhD degrees in chemical engineering from Caltech. Following completion of postdoctoral training in cancer immunotherapeutics and tumor immunology at City of Hope, he spent 15 years working within the pharmaceutical industry across a variety of functions including formulation, process development, and quantitative pharmacology. While at Pfizer, he led the creation of pharmacokinetic (PK)-pharmacodynamic (PD) model frameworks to support the targeted protein degradation portfolio. His research laboratory at UNC combines mechanistic modeling and dynamic cell-based assays as an animal-alternative approach to improve the translatability of preclinical studies and to unlock the potential of functional precision medicine through in vitro/ex vivo drug testing and dose optimization.
Kyle Mangano
Amgen
VIPER-TACs leverage viral E3 ligases for disease-specific targeted protein degradation.
Kyle Mangano is a native Rhode Islander who received his bachelor’s degree from McGill University. He leveraged his proximity to Cambridge, MA to work at two small biotechnology companies developing stapled peptides and nanoparticles, respectively. He then obtained his PhD from the University of Illinois at Chicago in Pharmaceutical Sciences. His graduate studies focused on the elucidating the mechanism of action of protein synthesis inhibitors using next generation sequencing. Kyle joined Amgen’s Induced Proximity Platform as a postdoctoral researcher in 2022, where he has been using chemical biology and genomic engineering to study targeted protein degradation.
November 7th, 2024
Host: Zuzanna Kozicka
Georg Winter
CeMM
When inhibitors degrade: supercharging of native protein turnover.
Georg is a chemical biologist and principal investigator at CeMM. Thematically, his lab works at the interface of chemical biology, cancer, and gene control. His group aims to innovate novel pharmacologic strategies to probe, understand and disrupt aberrant transcriptional circuits in cancer. Dr. Winter’s research strategy is driven by high-throughput and unbiased technologies. Connecting these technologies with synthetic chemistry empowers the understanding of the mechanism of action of proteins, protein complexes and small molecules. Currently, the main focus of the group is to explore the concept of proximity-inducing small molecules including small-molecule degraders. Dr. Winter is author on more than 60 manuscripts and he is a scientific co-founder of Proxygen and Solgate. His group is supported by several national and international grants including an ERC Starting Grant and an Aspire Award from the Mark Foundation. Dr. Winter’s contributions to the field of targeted protein degradation were acknowledged via multiple awards, including the Tetrahedron Young Investigator Award, the EFMC Prize, and the Eppendorf Award for European Scientists.
November 21st, 2024
Host: Breanna Zerfas
Jaimeen Majmudar
Pfizer
A Covalent, allele specific monovalent degrader for the treatment of MAFLD.
Jaimeen Majmudar is an Associate Research Fellow in Chemical Biology group at Pfizer. Jaimeen completed his Ph.D. in Medicinal Chemistry and Molecular Pharmacology at Purdue University in 2012 working on designing inhibitors to a membrane-bound methyl transferase, ICMT, that modifies KRAS. Following this, he moved to the University of Michigan for his postdoctoral work in Chemical Biology and Chemical Proteomics, where he was awarded the American Heart Association Research Fellowship. Jaimeen worked on developing new tools for the detection of transient cysteine modifications on proteins, development of tools for DIA-MS workflows, interrogating protein palmitoylation and characterizing cellular target engagement and selectivity of lipase inhibitors. Jaimeen enjoys better understanding what small molecules do in cells and the elucidation of the mechanisms that can lead to drugs to help patients in need. Outside of work, Jaimeen enjoys spending time with his family, yard work and growing vegetables that rabbits won’t feast on.
Matt Patricelli
Vividion
Suppression of NRF2-dependent cancer growth by a covalent allosteric molecular glue
Matt Patricelli has been characterizing the covalent interaction of small-molecules and proteins for more than 25 years, from basic mechanistic studies in the pre-proteomic era, to leading the development of covalent drugs against difficult to drug targets using chemoproteomics technologies. Dr. Patricelli is currently the Chief Scientific Officer at Vividion Therapeutics where he was a founding scientist and the first employee. Efforts at Vividion have led to three first in class clinical programs in oncology to date, and a deep pre-clinical pipeline in immunology and oncology. Prior to Vividion, Dr. Patricelli served as the Senior Director of Biology at Wellspring Biosciences where he led several drug discovery programs including the KRAS-G12C covalent inhibitor discovery project. From 2000-2012 he led the chemical proteomics platform activities at ActivX Biosciences. He was the first scientist to join ActivX and played a key role in the development of ActivX’s platform technologies, including establishing the KiNativ platform which operated as a successful commercial screening service for more than 15 years. Dr. Patricelli obtained his B.Sc. in biochemistry from McGill University, and Ph.D. from The Scripps Research Institute as the first graduate student of Dr. Benjamin Cravatt. He is an author or co-author of more than 30 scientific publications and three issued patents.