Previous Speakers (2022 part 2)
Some seminars were recorded and accessible for a limited time on our youtube channel.
January 5th, 2023
Host: Katherine Donovan
Chemical Rewiring of Cancer Drivers to Activate Apoptosis
Sai Gourisankar is a PhD student in Gerald Crabtree’s laboratory at Stanford University. His studies developed chemical inducers of proximity to regulate endogenous chromatin and transcriptional regulators in genetically unmodified cells, using a combination of biochemical, genomic, and chemical approaches in collaboration with the laboratory of Nathanael Gray. Prior to joining Stanford in 2017 and studying chemical biology, Sai acquired an MPP from University of Oxford and originally obtained both a B.S. and a B.A. in Chemical Engineering and Liberal Arts from the University of Texas at Austin.
University of Dundee
Discovery of XL01126: a PROTAC degrader of Leucine Rich Repeat Kinase 2
Xingui is currently a Marie Skłodowska-Curie fellow in Prof. Alessio Ciulli’s lab at the Center for Targeted Protein Degradation (CeTPD), where she is focusing her research on developing PROTAC degraders of Leucine Rich Repeat Kinase 2 (LRRK2), a promising target for Parkinson’s disease. Before joining the Ciulli group, she was a Postdoc associate at the University of Florida working with Prof. Guangrong Zheng and Prof. Daohong Zhou. At the University of Florida, she was part of a team that developed very effective BCL-XL/BCL-2 PROTAC degrader molecules. One of which was licensed to the Dialectic Therapeutics and led to the development of one of the first VHL-based PROTACs to enter the clinic and to be dosed in human patients for the treatment of hematological malignancies. She completed her PhD in Guangrong Zheng’s lab at University of Arkansans for Medical Sciences, where she designed, synthesized, and characterized delta-tocotrienol based radio-protectors.
Link to the recorded seminar: https://youtu.be/v_GUzZeoYXg
January 19th, 2023
Host: Mikolaj Slabicki
Molecular glue degraders of cyclin K and the emerging rules for molecular glue design
Zuzanna is a very recent PhD graduate working in the laboratory of Nicolas Thomä at the Friedrich Miescher Institute in Basel, Switzerland. She has an avid interest in molecular glue degraders and, more generally, in understanding how changes in protein interactomes can be brought about by the binding of small molecules. Prior to joining the Thomä lab in late 2018, Zuzanna obtained an Integrated Masters degree from the University of Edinburgh and during her studies she undertook various research projects, including with Nenad Ban at ETH and with Alessio Ciulli at the University of Dundee.
Host: Radek Nowak
HiBit-SpyTag: A minimal tag for covalent protein capture and degrader development.
Breanna Zerfas is currently the biochemistry and structural biology group leader and a senior scientist at the Center for Protein Degradation (CPD) in the Dana-Farber Cancer Institute. She received her PhD in chemical biology from Boston College in 2017, working with Prof. Jianmin Gao on the design and synthesis of unnatural peptide antibiotics. From there, Breanna moved to the Department of Medicinal Chemistry and Molecular Pharmacology at Purdue University as a post-doc with Prof. Darci Trader. While at Purdue, her research focused on the screening and development of fluorescence-based probes selective for various isoforms of the proteasome to be used in live cells. In the spring of 2020, Breanna moved back to Boston and joined the CPD, where her work primarily focuses on the development of new assays and chemical biology tools for target identification and high throughput screening.
February 2nd, 2023
Host: Breanna Zerfas
Fred Hutchinson Cancer Center
Targeting kinases for destruction in cancer
Behnam Nabet, Ph.D. is an Assistant Professor in the Human Biology Division at Fred Hutchinson Cancer Center. He received his Ph.D. in Cancer Biology from Northwestern University and B.A. in Biology from the University of Pennsylvania. He performed his postdoctoral studies in the laboratories of Dr. Nathanael Gray and Dr. James Bradner at Dana-Farber Cancer Institute and Harvard Medical School. Dr. Nabet’s laboratory is focused on developing strategies to target oncogenic signaling by controlling protein homeostasis. He pioneered the development of a versatile technology platform known as the dTAG system to rapidly degrade any target protein. The dTAG system facilitates biological exploration and drug target validation in cells and animal models. Dr. Nabet’s work has led to the development of selective agents targeting several cancer drug targets including FAK, PIN1, and DCLK1. These promising compounds inhibit critical vulnerabilities in translational models of cancer and are under continued development as novel therapeutics. Dr. Nabet has been recognized with several scientific honors, including a Claudia Adams Barr Program for Innovative Cancer Research award, an American Cancer Society Postdoctoral Fellowship, a Katherine Loker Pinard Endowed Fellowship, and an NIH/NCI K22 Transition Career Development Award.
Discovery and Optimization of CBL-B Inhibitors
Fred Cohen is Head of Medicinal Chemistry at Nurix Therapeutics. He has more than 20 years of experience in small molecule drug discovery, spanning multiple therapeutic areas including oncology, neurodegeneration and antibiotics. Prior to joining Nurix, he served at Achaogen, Genentech, and Tularik. Dr. Cohen earned his bachelor’s degree in Chemistry from Occidental College and his Ph.D. in Chemistry from the University of California, Irvine.
February 16th, 2023
Host: Mikolaj Slabicki
Harvard Medical School
High through-put interrogation of the UPS
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.
March 2nd, 2023
Host: Hojong Yoon / Radosław Nowak
RNA is a molecular glue that mediates HIV-1 Vif antagonism of human APOBEC3G
John Gross is a professor of Pharmaceutical Chemistry at UCSF. The Gross lab focuses on studying the control of mRNA decay and protein turnover in normal and virally infected cells. He received his PhD in Physical Chemistry at MIT, developing methods for biological solid-state NMR under the guidance of Professor Bob Griffin. Then he did his postdoctoral fellowship in Gerhard Wagner’s lab at Harvard Medical School, studying mRNA translation initiation, and joined the faculty of UCSF in 2004.
Link to the recorded seminar: https://youtu.be/q-b8K-UjZj4
Regulated Induced Proximity Targeting Chimera (RIPTACTM) Therapeutics: Chemical Biology Proof-of-Concept and Application in Prostate Cancer
Kanak Raina is a Director in the Biology Department at Halda Therapeutics. Dr. Raina received his PhD from the laboratory of Prof. Craig Crews at Yale University in 2014, where he worked on the manipulation of cellular proteostasis using small molecules. Following his PhD, Dr. Raina transitioned to drug discovery in the industry setting by moving to Arvinas, where he was biology lead on several exploratory pipeline TPD programs. Following a stint working on ER stress pathway inhibitors at Quentis Therapeutics, Dr. Raina moved to Halda in 2019, where he has been involved in the conceptualization of novel heterobifunctional small molecule therapeutics, and is leading biology efforts on the company's RIPTAC Therapeutic program for prostate cancer."
March 16th, 2023
Host: Breanna Zerfas / Radosław Nowak
Oxford Institute for Radiation Oncology
Neomorphic mutations in E3 ubiquitin ligases to divert substrate specificity
Vincenzo D’Angiolella is an Associate Professor at the Oxford Institute for Radiation Oncology. His research group focuses on understanding the role of the ubiquitin system in cancer pathogenesis and response to treatment with chemo- and radiotherapy. He is currently holding two programme grants from the Cancer Research UK (CRUK) and Medical Research Council (MRC), focused on the role of Cullin Ring ubiquitin Ligases (CRLs) in brain cancers (medulloblastoma and glioblastoma) pathogenesis. Studies from his laboratory have uncovered the mechanism of action and function of Fbxl17 in medulloblastoma (Raducu et al., 2016) and highlighted a novel synthetic lethal interaction between cyclin F loss and Chk1 kinase inhibition (Burdova et al., 2019). More recently, the laboratory has identified that mutations occurring on the E3 ligase KBTBD4 in medulloblastoma change substrate specificity driving the recognition of the chromatin remodelling complex CoREST (Chen et al., 2022). This work describes the first neomorphic mutation in an E3 ubiquitin ligase and elucidates a novel mechanism of tumorigenesis in medulloblastoma. Vincenzo has a Medical Degree (MD) from the University of Naples “Federico II” and completed his PhD at the same University in the field of General Pathology. During his PhD utilizing X. Laevis as a model system, he investigated the process of mitosis and spindle checkpoint (D'Angiolella et al., 2001; D'Angiolella et al., 2003; D'Angiolella et al., 2007) Following the completion of his studies, he worked as a postdoctoral fellow at the New York University School of Medicine in the USA in the laboratory of Professor Michele Pagano. During the postdoctoral studies, he elucidated the mechanism-of-action and function of cyclin F, the founding member of the F-box proteins. He uncovered that cyclin F does not partner with Cyclin Dependent Kinases (CDKs) like other cyclins do, but acts as an E3 ubiquitin ligase, forming a canonical CRL1 (D'Angiolella et al., 2012; D'Angiolella et al., 2010).
Link to the recorded seminar: https://youtu.be/VO0qT_hrgh8
Discovery of novel covalent E3 ligase ligands for degrader design
Dr. Dongwen Lyu (Lv) is an Assistant Professor/Research in the department of Department of Biochemistry and Structural Biology at UT Health San Antonio. His current research addresses two broad topics. The first topic is to study the cellular and molecular mechanisms of aging and age-related diseases and discover new senolytic drugs which can selectively eliminate senescent cells to treat aging and age-related diseases. The second topic is to study the mechanism of cancers and develop small molecules including covalent and non-covalent inhibitors and proteolysis targeting chimeras (PROTACs) degraders to treat cancers. He has published 42 peer-reviewed papers. His work includes the development of the first-generation selective BCL-XL PROTAC degrader (DT2216) and the second-generation BCL-xL and BCL-2 dual-degrading PROTAC (753b). DT2216 is currently being investigated as a novel anticancer agent in a Phase-1 clinical trial at Dialectic Therapeutics. Most recently, he led an interdisciplinary team to build new assays for target identification and validation, and to discover new E3 ligase ligands to extend the frontiers of targeted protein degradation.
Link to the recorded seminar: https://youtu.be/G-mAz1x1sj8
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
Targeted Degradation via direct 26S Proteasome Recruitment
Erin Dueber is a Distinguished Scientist and the Director of the Biological Chemistry Department at Genentech. Erin received her Ph.D. in Biophysics from UCSF (Prof. David Agard, thesis advisor) and completed an independent Miller Postdoctoral Fellowship at UC Berkeley (Prof. James Berger, host). She joined Genentech in 2008 where she has worked primarily on discovery projects aimed at understanding the molecular mechanisms underlying cell signaling pathways. These efforts include determining the mechanism of action of IAP antagonists, the structure and activation mechanism of TBK1, the activation and pore-forming mechanism of GSDMD, the activation and inhibition mechanisms of USP7 and demonstrating proof-of-concept target degradation via direct 26S Proteasome recruitment.
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.
May 25th 2023
Host: Breanna Zerfas
St Jude Children’s Research Hospital
PROTACs and Molecular Glues for pediatric cancers
Zoran is director of chemistry at St Jude. Prior to joining St. Jude in late 2016, Zoran was medicinal chemistry director and research fellow in Organon, Schering-Plough, Merck and most recently Eli Lilly. During his industrial career Zoran directed teams that delivered clinical candidates over a range of therapeutic areas including oncology, neurodegeneration, psychiatry and cardiovascular disorders. Zoran authored and co-authored over 100 scientific publications, patents, and book chapters. Since joining St. Jude Zoran’s research interests focus on the development of small molecule epigenetic modulators and protein degraders for the treatment of pediatric cancers such as medulloblastoma and acute leukemia.
Novel, reversible DCAF1 ligands expand the TPD-toolbox
Anna Vulpetti has over 25 years of experience in drug discovery in Pharma, at Pharmacia & Upjohn, Pharmacia, Pfizer, and since 2006 at Novartis. She is an Associate Director and Senior Principal Data Scientist in the Global Discovery Chemistry department at Novartis with experience from hit finding technologies to hit-to-lead optimization. By working interdisciplinary across different disease areas, she impacted multiple pipeline projects through molecular designs and knowledge in structural chemistry and biophysics.
Martin Schröder is a structural biologist with several years of experience in chemical biology and drug discovery. He is currently working as an Innovation Fellow in the Chemical Biology and Therapeutics department at Novartis with a focus of structure-guided drug design. While working in his PhD with the SGC, he contributed to the development and characterization of several chemical tool compounds. At Novartis he presently supporting several projects by providing biophysical assays and structural insights in ligand-protein complexes.
June 8th 2023
Host: Mikolaj Slabicki / Radek Nowak
Mechanism of cellular response to PDE3A-SLFN12 complex formation.
Heidi Greulich received her undergraduate degree from Princeton University, her PhD from The Rockefeller University, and embarked upon a career in cancer research spanning academia, industry, and collaborations between the two. Upon joining the Dana-Farber Cancer Institute and the Broad Institute, Dr. Greulich focused on discovery and characterization of oncogenic kinase mutations from human tumor samples, including mutations of EGFR, ERBB2, FGFR2, and ARAF. As a Senior Group Leader at the Broad, Dr. Greulich led the collaborative development of a selective EGFR exon 20 insertion inhibitor now in clinical trials, as well as the discovery and development of a new class of small molecules, the velcrins, that kill cancer cells by inducing complex formation between PDE3A and SLFN12. Most recently, her group has focused on the mechanism of action of cellular response to PDE3A-SLFN12 complex formation.
University of Barcelona
Understanding cooperativity effects in the drug-dependent degradation of the Cereblon neosubtrate CK1 alpha.
Dr. Juárez-Jiménez is a Lecturer in Physical Chemistry at the Faculty of Pharmacy of the University of Barcelona and the group leader of the Computational Molecular Design Lab. He obtained his PhD by the University of Barcelona in 2014 for Modelling in Drug Design. He conducted post-doctoral stays at the University of Florida (2015) and University of Edinburgh (2015-2020). His research focuses on using biomolecular simulations in the field of Computer Aided Drug Design, with a particular interest in how CADD can be useful to generate rational approaches for the design of small molecules that induce protein proximity.
June 22nd 2023
Host: Breanna Zerfas
Anthony W. Partridge
Formerly at MSD Singapore, currently at Genentech
Targeted degradation of PCNA outperforms stoichiometric inhibition to result in programed cell death.
Anthony Partridge joined Genentech in January 2023 as a Senior Director & Senior Principal Scientist in BCP where he leads small molecule efforts, with a focus on oncology. Previously, Anthony was VP of Discovery Biology and Pharmacology at Roivant Sciences, where he led a multidisciplinary group focused on program biology, biochemical and cellular assays, biophysics, protein production, and structural biology. His team advanced a variety of small molecule and degrader programs in the oncology and autoimmune arenas. From 2014 to 2021, was a Senior Principal Scientist at MSD Singapore where he led programs in the early discovery space, with an emphasis on degrader programs, macrocyclic peptides, and mRNA approaches. Prior to that, he was Senior Director of Biology at Pharmaron Beijing where he led a team focused on assay development/validation, screening, and built a world-class compound management facility. As an In Vitro Pharmacology Capability Lead at Merck, he pioneered collaborative efforts with pharmacology-based CRO partners. He also served as a Senior Scientist in the Pharmacology group at Merck Montreal. Anthony began his industry-based career at Élan Pharmaceuticals in San Francisco. He received his B.Sc. from the University of Guelph (1998), his Ph.D. from the University of Toronto (2003) and completed post-doctoral training at Scripps/UCSD (2003-2006).
Drugging the Chromatin Regulatory System
Steven Bellon, PhD, Chief Scientific Officer, joined Foghorn Therapeutics in 2016. He brings to the role more than 20 years of drug discovery experience from multiple target classes. Before joining Foghorn, Steven was executive director and head of structural biology, and lead in discovery and project management at Constellation Pharmaceuticals. At Constellation, he built the structural biology group, built and co-led the bromodomain platform efforts in collaboration with Genentech, and was a member of the portfolio management committee. Steven has a passion for drugging novel targets and has contributed to many drug discovery efforts in oncology including those for p38, HCV helicase, cMet, BET, EZH2, and numerous bromodomains. Prior to his work at Constellation, he held positions of increasing responsibility at Amgen and Vertex Pharmaceuticals. Steven received a PhD in physical chemistry from MIT under the direction of Stephen Lippard and then completed postdoctoral training at Yale University with Thomas Steitz, funded by a Damon Runyon fellowship
July 6th 2023
Host: Katherine Donovan / Mikołaj Słabicki
Institute of Molecular Biology of Barcelona
Development of proteolytic chimeras based on direct 26S proteasome targeting.
Dr. Bernat Crosas obtained his PhD in the Autonomous University of Barcelona (UAB), on Structure-function studies and enzymatic regulation of retinoid signaling, at the department of Biochemistry and Molecular Biology. After that, in 2001, he moved, as a postdoctoral Fellow, to Harvard Medical School, at the Proteasome lab of the Cell Biology Department, led by Prof. Finley lab. By 2009, he obtained a group leader position at the Institute of Molecular Biology of Barcelona, part of the CSIC. His interests are focused on the characterization of the complexity of regulated degradation pathways, with special attention on the proteasome regulation and targeted protein degradation, with many contributions in the understanding of proteasome function and regulated protein degradation. Teaming up with biotechnological companies and with the Institute of advanced chemistry of Catalonia (IQAC) he has focused his interests on the development of novel proteolytic chimeras with therapeutic applications, in collaboration with other research groups from academia and pharmacy.
A chemical degron marks C-terminally modified proteins for degradation.
As a graduate student, I studied transcriptional regulation by MYC and BET bromodomain proteins in the lab of Johannes Zuber at the IMP Vienna (DOI: 10.1126/science.aao2793). Having used degrons as genetic tools left me fascinated for endogenous mechanisms of selective protein degradation. For my postdoc, I therefore joined the lab of Jacob Corn at ETH Zürich in 2019 to combine high-throughput genetics and chemical biology tools to explore mechanisms of chemical quality control.
July 20th 2023
Host: Hojong Yoon / Mikołaj Słabicki
Constitutive protein degradation induces acute cell death via proteolysis products.
Si-Han Chen was born and raised in Taiwan, where she completed her undergraduate and master's degrees. Subsequently, she relocated to the Bay Area to pursue a Ph.D. in Biophysics at the University of California - San Francisco. During her doctoral studies, Si-Han focused on investigating host-pathogen interactions and ubiquitin ligases, providing valuable insights into the inter-regulation of Cullin-RING ligases. Following her Ph.D., Si-Han joined Genentech as a postdoctoral fellow under the guidance of Dr. Ingrid Wertz. During this time, she delved further into the complexities of ubiquitin-proteasome biology, leading to unexpected discoveries concerning protein degrader mechanisms of action. Si-Han will share these exciting findings during her upcoming seminar. In November 2022, Si-Han joined Bristol Myers Squibb as a Senior Scientist based in San Diego. She continues her research in the field of protein degraders and small molecule drug discovery.
Cellular determinants of targeted membrane protein degradation by lysosome targeting chimeras.
Green Ahn received her undergraduate degree from University of Southern California, and completed her PhD at Stanford University in the lab of Prof. Carolyn Bertozzi. In the Bertozzi lab, Green developed and elucidated the mechanisms of lysosome targeting chimeras (LYTACs) to degrade extracellular and membrane proteins. She will start as a postdoctoral fellow in Prof. David Baker’s lab at the Institute for Protein Design in University of Washington.