Previous Speakers (2023 part 2)
Some seminars were recorded and accessible for a limited time on our youtube channel.
Hybrid Meeting: In-Person and over Zoom
September 14th, 2023
12.00-12.30 pm Arrival and Registration
12:30 -12:35 pm Welcome Remarks - Dana-Farber Targeted Protein Degradation Organizing Committee
12:35 -1:30 pm Bill Sellers, Broad Institute
“Towards a more systematic understanding ubiquitin ligases and their therapeutic utility”
1:30 - 2:00 pm Fleur M. Ferguson, UCSD
“Interrogating the Druggable Proteome with Proximity Pharmacology”
2:00 - 2:30 pm Jonathan Tsai, DFCI
“A Common Pathway of Hormone Receptor Degradation: UBR5”
2:30 - 3:30 pm Light Snack / Coffee Break
3:30 - 4:15 pm Flash Talks
Katherine Donovan, DFCI, “Chemoproteomic profiling surveys the degradable proteome”
Kevin Dong, HMS, “Reinventing covalent drug discovery for the UPS via multiplexed targeted proteomics”
Ditsa Sarkar, MGH, “Developing a cell therapy suicide switch using targeted protein degradation.”
Nikki Kong, Center for Protein Degradation, DFCI, "Employing phenotypic assays to dissect on-target mechanisms of molecular glue degraders."
4:15 - 5:00 pm Panel Discussion: Danette Daniels, Lyn Jones, Sara Buhrlage
5:00 – 5:30 pm Stephen Elledge, HMS
“Finding Ubiquitin-Dependent and Independent Degrons.”
5:30 – 8:00 pm Reception (Appetizers and Open Bar)
Event Location: Linda K. Paresky Conference Center, Simmons College 300 Fenway Boston, MA 02115
The entire event will also be streamed via our standard Zoom link. Please, register only if are able to attend the seminar in person:
Speakers:
William R. Sellers
Broad Institute
Towards a more systematic understanding ubiquitin ligases and their therapeutic utility
Dr. Sellers is a Core Institute Member and Director of the Cancer Program at the Broad Institute and a Professor of Medicine at the Dana-Farber Cancer Institute and Harvard Medical School. At the Broad Institute he directs a research group focused on translating genomic discoveries into new therapeutics. His lab is focused on both functional genomic approaches to understanding routes for therapeutic development including digenic paralog CRISPR screens, and systematic gain-of-function lethality screens, and on creating new routes for developing therapeutics and understanding therapeutic action. Previously, Dr. Sellers directed cancer drug discovery and early cancer clinical development at the Novartis Institutes for Biomedical Research overseeing all cancer research and clinical sites from 2005-2016. During this time > 30 small molecule, biologic and cell-based cancer therapeutics entered first-in-man trials. Ten therapeutics have reached market approval including encorafinib, alpelisib, ribociclib, asciminib and tisagenlecleucel. During this tenure, he conceptualized and directed the development of Cancer Cell Line Encyclopedia, the Novartis Primary Derived Xenograft Encyclopedia and of large-scale efforts to functionally characterize the cancer genome (Project DRIVE). He previously was an Associate Professor of Medicine at the Dana-Farber Cancer Institute and Harvard Medical School and an Associate Member of the Broad Institute. Together with Matthew Meyerson, he initiated and developed large-scale efforts to resequence genes in diverse cancer types. In addition they pioneered the use of high-density SNP arrays for defining LOH and copy number alterations across cancer including the development of the widely used GISTIC algorithm. These projects led to discovery of EGFR mutations in lung adenocarcinoma and the discovery of the oncogenic role of the MITF gene in melanoma. In addition, his work advanced the understanding of the molecular mechanisms of growth regulation of the PTEN tumor suppressor gene. Dr. Sellers was a member of the National Cancer Advisory Board. Dr. Sellers received his B.S. from Georgetown University in 1982 and M.D. from the University of Massachusetts Medical School in 1986. He completed residency training in Internal Medicine at the University of California San Francisco in 1989 and trained in Medical Oncology at the Dana-Farber Cancer Institute.
Fleur Ferguson
University of California, San Diego
Interrogating the Druggable Proteome with Proximity Pharmacology
Fleur Ferguson received her M.Sc degree in chemistry from Imperial College London, where she received the Department of Chemistry prize for overall excellence. Dr. Ferguson received her Ph.D in Chemistry from the University of Cambridge funded by a BBSRC studentship, advised by Prof. Chris Abell and Prof. Alessio Ciulli. She then joined DFCI, where she performed her postdoctoral research in the laboratory of Prof. Nathanael Gray. Here, her research focused on modulating kinases with reversible inhibitors, covalent inhibitors, and targeted protein degradation, as well as applying TPD to undruggable targets in neurodegeneration. Dr. Ferguson is currently an Assistant Professor in the Department of Chemistry and Biochemistry, and the Skaggs School of Pharmacy and Pharmaceutical Sciences, at the University of California, San Diego. Her research group focuses on the development and application of proximity-pharmacology technologies to disease areas where traditional targeted therapies have failed, such as neuro-oncology and neurodegeneration. Research in the Ferguson lab has been recognized by numerous prestigious awards including the NIH Directors’ New Innovator Award, the Keck Foundation Research Award, and new investigator awards from the Alzheimer’s Association and the Hilblom Foundation.
Jonathan Tsai
Dana-Farber Cancer Institute/Brigham and Women's Hospital
A Common Pathway of Hormone Receptor Degradation: UBR5.
Jonathan is an Instructor in Pathology at the Brigham and Women's Hospital and postdoctoral scholar in the laboratory of Benjamin Ebert in the Dana-Farber Cancer Institute. He received his MD and PhD from Stanford University. He is broadly interested in protein degradation and its effects on transcriptional regulation and has focused on nuclear hormone receptors as a model for ligand dependent degradation. His long-term goal is to understand and modulate the interaction between the proteasome machinery and hormone receptors with applications towards development, immunology, and cancer biology.
Katherine Donovan
Dana-Farber Cancer Institute/Harvard Medical School
Chemoproteomic profiling surveys the degradable proteome.
Katherine Donovan is a Lead Scientist in the Fischer Lab at Dana-Farber Cancer Institute/Harvard Medical School where she works on the development of molecular-glues and PROTAC molecules for targeted protein degradation. She completed her PhD training in protein biochemistry and structural biology in the lab of Prof Renwick Dobson 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 led proteomics teams focused on degrader screening and target identification in the Fischer Lab as well as in the Center for Protein Degradation. She has used proteomics technology to identify the degradation targets of many molecules including the identification of SALL4 as the protein likely underlying the teratogenicity of thalidomide. Katherine led a large effort to map the degradable kinome and now to aid her quest to map the degradable proteome she has recently started a public degradation proteomics initiative which provides free target mapping of degraders. In recognition of her efforts in the TPD field, Katherine was awarded the Arvinas TPD Early Researcher Award in 2022. Katherine continues to manage and work on several projects related to ligase biology and protein degradation and oversees the TPD proteomics operation in the Fischer Lab and Center for Protein Degradation
Kevin Dong
Harvard Medical School
Reinventing covalent drug discovery for the UPS via multiplexed targeted proteomics.
Kevin Dong is a graduate student in the Biological and Biomedical Sciences PhD program at Harvard Medical School. In the Gygi lab, he develops chemoproteomic platforms that systematically reveal the cellular degradome and rapidly discover chemical probes that target proteins within the ubiquitin-proteasome system (UPS). Powered by an alarming amount of Starbucks coffee, TMT reagents, and a vision for a healthier future, Kevin strives to develop the next-generation of UPS-centric precision medicines.
Ditsa Sarkar
Massachusetts General Hospital
Developing a cell therapy suicide switch using targeted protein degradation.
Ditsa joined Jan lab at MGH in 2022 as a Postdoctoral fellow with a focus on refining cell therapies by harnessing elegant protein degradation machinery. Prior to this, she completed her doctoral training in Biochemistry and Biophysics at National Institute of Immunology, India. Outside work, Ditsa enjoys hiking, EDM & painting.
Nikki Kong
Center for Protein Degradation, Dana-Farber Cancer Institute
Employing phenotypic assays to dissect on-target mechanisms of molecular glue degraders.
Nikki Kong received my PhD in molecular and cell biology from UC Berkeley in the Tjian lab, where as an NSF Graduate Research Fellow, she studied transcriptional regulation of lymphoid-specific hematopoietic differentiation. Nikki Kong then received an NIH T32 fellowship to further her training in Chai and Tenen labs at Brigham and Women’s Hospital/Harvard Medical School. During her postdoctoral training, she determined the DNA binding domain of the transcription factor SALL4, as well as how it interacts with co-factors to regulate transcription in hepatocellular carcinoma cells. Currently, Nikki Kong is the Biology Group Leader at the Center for Protein Degradation at Dana-Farber Cancer Institute. Her group performs phenotypic screens and target validation experiments in order to discover novel molecular glue degraders.
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Stephen J. Elledge
Harvard Medical School/Brigham and Women’s Hospital
Finding Ubiquitin-Dependent and Independent Degrons.
Stephen J. Elledge is the Gregor Mendel Professor of Genetics and Medicine at Harvard Medical School and the Brigham and Women’s Hospital Division of Genetics, and is a Howard Hughes Medical Institute Investigator. He received his B.S. in chemistry from the University of Illinois and his Ph.D. in biology from the Massachusetts Institute of Technology. He began his laboratory at the Baylor College of Medicine in Houston and moved in 2003 to the Brigham and Women’s Hospital and Harvard Medical School Department of Genetics. He is an elected member member of the National Academy of Sciences, National Academy of Medicine, and American Academy of Arts and Sciences. His many awards include the Dickson Prize (2010), Lewis S. Rosenstiel Award for Distinguished Work in the Basic Medical Sciences (2013), Gairdner Foundation International Award (2013), Albert Lasker Basic Medical Research Award (2015), Breakthrough Prize in Life Sciences (2017) and the Gruber Prize in Genetics (2017).
Dr. Elledge’s research interests center on genetic approaches to biological problems including the study of proteins that sense and respond to DNA damage, and regulate the cell division cycle and cancer. Through this work he uncovered a protein kinase cascade that is now known as the DNA Damage Response. He discovered F-box proteins and Skp1 and along with Dr. Wade Harper, uncovered the two largest families of E3 ubiquitin ligases: the cullin-RING ligases (CRL), starting with the Skp1-Cul1-F-box sub-family, and the RING domain ligases. He has also worked in unraveling the role of cancer drivers in the evolution of cancer through aneuploidy and how tumor suppressors allow cancers to evade the immune system. More recently Dr. Elledge has developed a suite of immunological methods, such as T-Scan, VirScan and EpiScan, that allows the genome-wide identification of epitopes recognized by B and T cells. He has used these tools to investigate the role of viruses in human disease such as Measles, MS and COVID-19.
Panelists:
Danette Daniels
Foghorn Therapeutics
Danette L. Daniels, Ph.D. is a Vice President of the Protein Degrader Platform at Foghorn Therapeutics developing therapeutic degraders in the areas of chromatin biology and oncology. She was an early leader in the field of targeted protein degradation, pioneering approaches to monitor cellular kinetics of degradation, understand mechanism of action, and most recently, co-developing a new PROTAC modality. She received her PhD in Biophysics at Yale University and was a postdoctoral fellow at Stanford School of Medicine studying the Wnt signaling pathway.
Sara Buhrlage
Dana-Farber Cancer Institute
Sara Buhrlage, PhD is an Associate Professor holding joint appointments in the Dana-Farber Cancer Institute department of Cancer Biology and the Harvard Medical School department of Biological Chemistry and Molecular Pharmacology. Dr. Buhrlage’s research is focused on development of new chemical probes and therapeutic strategies for deubiquitinases (DUBs). Her research has provided new insights into the chemical tractability of DUBs, approaches for illuminating DUB function and therapeutic potential and roles of DUBs in cancer. Dr. Buhrlage earned a Doctor of Philosophy in organic chemistry from the University of Michigan and completed a post-doctoral fellowship at the Broad Institute.
Lyn Jones
Center for Protein Degradation at the Dana-Farber Cancer Institute
Lyn Jones completed PhD studies in synthetic organic chemistry at the University of Nottingham, before starting his postdoctoral research at The Scripps Research Institute, California in chemical biology. He joined Pfizer (Sandwich, UK) as a medicinal chemistry team leader, eventually becoming Director of Chemical Biology and Lead Discovery Technologies. He transferred to Pfizer Cambridge, MA to become Head of Rare Disease Chemistry and Head of Chemical Biology. He then joined Jnana Therapeutics as Vice President of Chemistry and Chemical Biology, before moving to his current role as Director of the Center for Protein Degradation at the Dana-Farber Cancer Institute in Boston. His research interests include the creation and application of chemistry-based technologies that advance therapeutic target identification and accelerate drug discovery. He is an elected Fellow of the American Association for the Advancement of Science, the Royal Society of Chemistry, the Royal Society of Biology, the Royal Society for Public Health, and the Linnean Society, and serves on the editorial board of the journal RSC Medicinal Chemistry and the board of the Medicinal and Bioorganic Chemistry Foundation.
Event sponsors:
September 21st, 2023
Host: Mikolaj Slabicki
William J. Gibson
Dana Farber Cancer Institute
Time Change:
11 am EDT/EST
8 am PT/PST
4 pm BST/BDT
5 pm CEST/CET
Bifunctional small molecules that induce nuclear localization and targeted transcriptional regulation
William J. Gibson MD,PhD is a medical oncology fellow at the Dana Farber Cancer Institute, where he is a Lubin Scholar. His research focuses on novel applications for chemical induced proximity and strategies to drug some of cancers most intractable targets. He is co-mentored by Stuart Schreiber and Matthew Meyerson.
He previously earned degrees in Biological Engineering and Philosophy at the Massachusetts Institute of Technology. He then joined the Harvard-MIT MD/PhD program, where he worked with Rameen Beroukhim on understanding cancer evolution and the therapeutic vulnerabilities of somatic copy number alterations. Gibson completed his residency in internal medicine at Brigham and Women's Hospital.
Yevgeniy Serebrenik
University of Pennsylvania and Children’s Hospital of Philadelphia
Pooled endogenous protein tagging and recruitment for scalable discovery of effectors for induced proximity therapeutics.
Yevgeniy Serebrenik is a postdoctoral fellow in the lab of Dr. Ophir Shalem at the University of Pennsylvania and Children’s Hospital of Philadelphia, where he developed a high-throughput approach for direct manipulation and visualization of endogenous proteins called Scalable POoled Targeting with a LIgandable Tag at Endogenous Sites (SPOTLITES). Yevgeniy used SPOTLITES to study endogenous proteins capable of degrading various targets upon induced proximity, as well as different protein quality control responses to spatially restricted protein misfolding enabled by combining optical sequencing with pooled hydrophobic targeting. This work was supported by F32 and K99 awards. Prior to his postdoc, he earned his B.S. from Tufts University in 2011 and completed his Ph.D. at Yale University in 2017. At Yale, Yevgeniy worked in the lab of Dr. Craig Crews using small molecule strategies to study protein quality control mechanisms in the Golgi apparatus.