Previous Speakers (2021 part 2)
Some seminars were recorded and accessible for a limited time on our youtube channel.
Dana-Farber Cancer Institute / Harvard Medical School
January 6th, 2022
Hijacking The Ubiquitin System for Protein Degradation Therapeutics
Host: Katherine Donovan
Eric Fischer, PhD, is Independent Investigator at Dana-Farber Cancer Institute and Associate Professor of Biological Chemistry and Molecular Pharmacology at Harvard Medical School. He is also the Director of the DFCI/Deerfield Center for Protein Degradation.
Dr. Fischer’s research focuses on understanding the molecular architecture, function, and regulation of complex cellular signaling machines and their involvement in cellular processes. His lab leverages this knowledge to develop new strategies for small-molecule-mediated modulation. Using biochemistry, chemical biology, and cell biology methods, his lab has contributed to the understanding of the efficacy and adverse activity of thalidomide and related drugs. Beyond defining the mechanism of action for this transformative cancer drug and solving a decade-old mystery of pharmaceutical sciences, this work inspired numerous projects that intend to utilize similar principles to redirect ligase activity to new targets. This represents a new therapeutic modality often referred to as targeted protein degradation. Dr. Fischer’s lab helped to establish this approach and has defined many of the underlying principles for small molecule degraders. Dr. Fischer’s work has been recognized with awards including, the Damon Runyon Cancer Research Foundation’s 2017 Damon Runyon-Rachleff Innovation Award, and the Mark Foundation’s 2018 Emerging Leaders Award. Dr. Fischer is a co-founder of Civetta Therapeutics, Neomorph, Inc and Jengu Therapeutics.
Dr. Fischer completed his undergraduate training at the Universities of Hamburg (Germany) and Basel (Switzerland) and completed doctoral training at the Friedrich Miescher Institute for Biomedical Research, also in Basel. Dr. Fischer joined the Dana-Farber faculty in 2015.
January 20th, 2022
Navigating the Challenges of Degrader Optimization
Host: Breanna Zerfas
Stew Fischer, Ph.D. joined C4 Therapeutics in May 2016 and has served as our Chief Scientific Officer since May 2018. Between May 2016 and May 2018, Stew served as our Senior Director of Discovery Sciences. Prior to joining C4 Therapeutics, Stew held senior leadership roles at the Broad Institute, including Director of Quantitative of Biochemistry and Enzymology, where he developed and implemented biochemical plans for therapeutic projects. He previously spent fifteen years at AstraZeneca in roles of increasing responsibility across target validation, drug discovery and clinical candidate support, including Executive Director of Infection Bioscience. Stew started his career at Hoffmann-La Roche as a Research Scientist after completing an NIH Post-Doctoral Fellowship at Harvard Medical School. Stew holds a Ph.D. in Organic Chemistry from the California Institute of Technology, and a B.A. in Chemistry from the University of Vermont.
Link to the recorded seminar: https://youtu.be/DRSDfswes0U
February 3rd, 2022
Host: Hojong Yoon
Targeted protein degradation elicited by branched ubiquitin code
Fumiaki Ohtake, Ph.D., is an Associate Professor at Hoshi University, Tokyo, Japan. His research group focuses on the molecular mechanism of protein ubiquitylation regulating cellular signaling pathways and proteostasis as well as chemically induced targeted protein degradation.
After completing his Ph.D. at the University of Tokyo, he started his research at the National Institute of Health Sciences in Japan, where he studied the acetylation of ubiquitin. In 2016, he moved to the Tokyo Metropolitan Institute of Medical Science. In collaboration with Dr. Keiji Tanaka and Dr. Yasushi Saeki, he found cellular roles of branched ubiquitin chains in proteasomal degradation and NF-kB signaling. In 2019, he set up his lab at Hoshi University as a P.I. and started studying the mechanism of targeted protein degradation from the view of the ubiquitin code biology.
Nathaniel Henning, Andrew Manford
University of California, Berkeley
Discovery of a Covalent FEM1B Recruiter for Targeted Protein Degradation Applications
Nathaniel Henning is a PhD student with Professor Daniel Nomura at the University of California, Berkeley. Nathaniel’s research in the Nomura group uses covalent ligand discovery platforms to explore new strategies for targeted protein degradation and additional induced-proximity modalities, including deubiquitinase-targeting chimeras (DUBTACs). Prior to joining the Nomura group, Nathaniel worked as a technician in Nathanael Gray’s group at the Dana-Farber Cancer Institute.
Andrew Manford received his B.S. from the University of California, Davis and completed his PhD in Biochemistry, Molecular, and Cell Biology at Cornell University in the lab of Scott Emr. Andrew is currently a postdoc with Michael Rape at the University of California, Berkeley. Andrew’s work in the Rape lab focuses on identifying and characterizing new roles for ubiquitin ligases in regulating cellular differentiation and metabolism. This research has led to the discovery of the reductive stress response, a pathway that controls mitochondrial activity and redox homeostasis through the ubiquitin ligase CUL2FEM1B.
4 Selected Trainee Short Talks
February 17th, 2022
Host: Katherine Donovan
Hemant Sistla - thinkMolecular Technologies
Structural Model of the ternary complex RNF114 - PROTAC - BRD4
Hemant Sistla completed his Masters in Physics from the Sri Sathya Sai Institute of Higher Learning, Puttaparthi, India. Currently, he is a Scientific Associate at thinkMolecular Technologies, a molecular simulations company based in Bengaluru. His work involves developing python based tools for data-mining and data-processing to make sense of the behaviors of various proteins and their complexes. Running Molecular Dynamics Simulations of these systems and analyzing the results are also part of his role at thinkMolecular Technologies (www.thinkmolecular.in).
Cyrille Kounde - Imperial College London
Conditional proteolysis with PROTACs: The art of taming the chimeras
Cyrille Kounde completed his B.Sc. degree in biochemistry at Paris Diderot University and his M.Sc. in medicinal chemistry at Paris Descartes University. In 2006, he started his career in industry in the United Kingdom as a drug discovery scientist at Evotec Ltd then joined Novartis UK in 2010. Subsequently, he moved to Novartis Singapore and worked on several medicinal chemistry projects tackling neglected infectious diseases. He returned to the UK in 2017 to pursue a PhD in the group of Prof. Ed Tate at Imperial College London. His research focuses on the conditional activation and targeted delivery of PROTACs.
Luke Simpson - MRC PPU, University of Dundee
A ligand-inducible affinity-directed protein missile (L-AdPROM) system for targeted proteolysis
Luke Simpson is a PhD student with Professor Gopal Sapkota in the MRC PPU (Medical Research Council Protein Phosphorylation and Ubiquitylation Unit) at the University of Dundee, UK. Luke’s doctoral research has centred around exploring technologies for targeted protein modification and has involved the combined use of nanobody-based and proteolysis-targeting chimera (PROTAC) technologies for targeted protein degradation (TPD).
Alexander Hanzl - CeMM Center for Molecular Medicine
Charting functional E3 ligase hotspots and resistance mechanisms to small-molecule degraders via chemical genetics
Alexander Hanzl is a PhD student in the laboratory of Georg Winter at the Center for Molecular Medicine in Vienna. His thesis revolves around understanding resistance mechanisms in targeted protein degradation as well as employing phenotypic screening to identify novel E3 ligases amendable to this novel therapeutic modality. Prior to joining CeMM in 2017, Alex obtained his MSc focusing on epigenetics at the FMI in Basel. He originally trained as a chemist and soon moved into chemical biology after his BSc degree.
March 3rd, 2022
Host: Mikolaj Slabicki
Massachusetts General Hospital
Chemical degraders of CBP and p300
Christopher Ott, PhD is an Investigator at the Massachusetts General Hospital's Center for Cancer Research. He joined the faculty of Harvard Medical School as an Assistant Professor in 2018. He and his research group focus on strategies to chemically modulate gene regulatory factors that control transcription through enhancers, with the goal of advancing these new tools as cancer therapeutics. Dr. Ott obtained his undergraduate degree from the University of Wisconsin-Madison and completed his doctoral dissertation in molecular genetics at Northwestern University. Before joining MGH he was a Leukemia & Lymphoma Society postdoctoral fellow in Jay Bradner's group at the Dana-Farber Cancer Institute. His work has been recognized by several awards including an NIH Pathway to Independence Award, an American Society of Hematology Scholar Award, and the V Foundation Scholar Award.
Francesca Ester Morreale
Research Institute of Molecular Pathology
“BacPROTACs mediate targeted protein degradation in bacteria”
Francesca Ester Morreale, PhD is a Postdoctoral researcher in Dr. Tim Clausen’s group at the Research Institute of Molecular Pathology (IMP), Vienna, Austria and a member of the Boehringer Ingelheim Discovery Research global postdoc program. Her research focuses on establishing targeted protein degradation technology in bacteria, by reprogramming components of bacterial protein degradation pathways.
Prior to joining the Clausen lab, she was a joint postdoc between Prof. Helen Walden and Prof. Alessio Ciulli research groups at the MRC Protein Phosphorylation and Ubiquitylation Unit, University of Dundee, UK. Dr. Morreale obtained her PhD in Pharmaceutical Sciences in 2014 from the University of Messina, Italy.
March 17th, 2022, 12PM (EDT) / 9 am (PT) / 4 pm (GMT) / 5 pm (CET).
Lenalidomide resistance mechanisms
Host: Mikolaj Slabicki
Jan Krönke is a professor of hematology and oncology at the Charité, Berlin since 2020. Dr. Krönke received an MD from Heidelberg University and completed his residency in hematology/ oncology at Ulm University Hospital where he studied genetics in AML. From 2011 to 2014 he joined the group of Benjamin Ebert at the Brigham and Women’s Hospital/ Harvard Medical School where he discovered that thalidomide analogs modulate the CRBN E3 ligase to induce ubiquitination and degradation of the neo-substrates IKZF1, IKZF3, and CK1α. After returning to Ulm University he became head of an Emmy Noether research group. His current research focuses on the development of new protein degraders, drug resistance mechanisms and proteomic studies in hematologic malignancies. For his work on targeted protein degradation, Dr. Krönke has been recognized by several awards including the Paul Martini prize and the Artur Pappenheim award.
University of Dundee
March 31th, 2022
Discovery of selective and orally available VHL-based degraders of BAF complex sub-units
Host: Radosław Nowak
William Farnaby is a Principal Investigator within the newly formed Centre for Targeted Protein at the University of Dundee. Since 2016, as part of the group of Alessio Ciulli, he has led a targeted protein degradation drug discovery team engaged in a collaboration between the University of Dundee and Boehringer Ingelheim. During this time Will has progressed a number of protein degradation projects through key drug discovery milestones and authored highly cited studies detailing novel approaches for the design and characterisation of degrader molecules. Prior to this Will worked at Takeda as a senior medicinal chemist, co-inventing Soticlestat and Luvadaxistat, inhibitors currently under late-stage clinical evaluation in the Central Nervous System therapeutic area. He is now initiating his own academic program focussed on using induced proximity chemistry for the discovery of chemical probes and methods of target validation, with a particular interest in generating tools that enable CNS research.
April 14th, 2022
Host: Breanna Zerfas
Kylie J. Walters
Proteasome substrate receptor Rpn13 as an anti-cancer target
Kylie Walters is a Senior Investigator and Section Chief in the National Cancer Institute of the National Institutes of Health, USA. Her laboratory merges structural, chemical and cellular biology approaches to define the mechanisms of regulated protein degradation, ubiquitin signaling, and protein quality control. Together with her collaborators and team members, she has made discoveries that have defined how the proteasome interacts with ubiquitinated substrates and ubiquitination machinery. Kylie began training in the field of biophysics as an undergraduate at Wesleyan University, obtained a Ph.D. in Biophysics from Harvard University, and was an American Cancer Society Postdoctoral Fellow in the Pathology Department at Harvard Medical School. She began her independent career at the University of Minnesota and then moved her group to the National Cancer Institute where her lab seeks to develop new therapies against cancer by modulating functions of the proteasome and proteasome-related proteins.
Proteo-Science Center, Ehime University
A proximity-dependent biotinylation method for molecular glues and PROTACs
Satoshi Yamanaka, PhD is a Postdoctoral researcher in Dr. Tatsuya Sawasaki’s group at the Proteo-Science Center (PROS), Ehime University, Japan. Dr. Yamanaka obtained his PhD in 2020 from the Ehime University. So far, he established biochemical assay system based on wheat cell-free system to detect thalidomide- and its derivatives-dependent interaction. In 2020, he developed ancestral BirA for proximity-dependent biotin identification (AirID) as a novel proximity-dependent biotinylation enzyme. Recently, he established a proximity biotinylation-based method to analyze protein–E3 ligase interactions induced by molecular glues- and PROTACs. His current research focused on the application these methods to development of new molecular glues and PROTACs.
April 28th, 2022
Covalent Small-Molecule Protein Degraders
Host: Katherine Donovan
Ekaterina (Katya) Vinogradova is an Assistant Professor and Head of the Laboratory of Chemical Immunology and Proteomics at the Rockefeller University since December 2020. Katya received her PhD from Massachusetts Institute of Technology with Prof. Stephen Buchwald, where she developed new organometallic methods for synthetic chemistry and chemical biology applications, including the development of an organometallic approach towards bioconjugation in collaboration with the laboratory of Prof. Bradley Pentelute (MIT), which started a joint program between the two research groups exploring “organometallic chemical biology”. She further pursued post-doctoral work as a Pfizer Fellow of Life Sciences Research Foundation with Prof. Benjamin Cravatt at the Scripps Research Institute. Her post-doctoral research focused on the development of an integrated chemical proteomic and phenotypic screening approach to create a global map of druggable protein targets in primary human T cells and to develop advanced small molecule probes that perturb the functions of these proteins, including small-molecule protein degraders. Katya’s current research applies chemical synthesis, cell biology and chemical proteomic tools toward the goals of discovering and characterizing (a) novel selective chemical probes that perturb the functions of key proteins regulating immunological and neuroimmunological processes; (b) new mechanisms for small molecule-induced protein degradation; and, more broadly, (c) the pharmacological landscape and signal transduction pathways in immune-related disorders.
Host: Hojong Yoon
May 12th, 2022
Institute of Molecular Pathology, Vienna BioCenter
Deciphering the regulation of essential genes through time-controlled CRISPR screens.
Johannes Zuber is a senior group leader at the Research Institute of Molecular Pathology (IMP) at the Vienna BioCenter (VBC) and Adjunct Professor at the Medical University in Vienna, Austria. He studied medicine and received a doctorate in molecular cancer research at the Charité Medical School in Berlin, Germany, where he also completed four years of clinical training in hematology and oncology. During his postdoctoral research at Cold Spring Harbor Laboratory he developed experimentally tractable leukemia mouse models and advanced shRNAmir-based screening tools, which he applied to identify and characterize chromatin-associated dependencies in cancer. At the IMP, Johannes Zuber and his team develop and apply innovative methods for loss-of-function genetic studies and screens (using inducible shRNAmir, CRISPR, and Degron systems) and time-resolved transcriptomics (using SLAM-seq) to identify and evaluate therapeutic targets in AML, other cancer subtypes, and tumor-associated T cells. He received an ERC Starting Grant, has been selected as an EMBO Young Investigator (YIP), and has been awarded with the German Cancer Prize in 2016.
Institute of Molecular Pathology, Vienna BioCenter
AKIRIN2 controls the nuclear import of proteasomes in vertebrates.
David Haselbach is a group leader at the Research Institute of Molecular Pathology (IMP) at the Vienna BioCenter (VBC). He studied biochemistry and physics at the university of Potsdam and Molecular Biology at the University of Göttingen, where he also performed his PhD studies. In his postdoc studies in the lab of Holger Stark he developed cryo EM Methods to analyze molecular dynamics and solved structures of multiple molecular machines such as the 26S proteasome or the spliceosome. At the IMP, the Haselbach lab is trying to understand how molecular machines in protein quality control work. Therefore, they use modern cryo EM methods such as in-situ cryoET and time resolved single particle EM.