The Webinar Series will take place bi-weekly on: Thursdays

12 pm noon (EDT)

9 am (PT), 5 pm (GMT), 6 pm (CET)

We will use a single Zoom webinar registration for the upcoming seminars:

https://dfci.zoom.us/webinar/register/WN_m7JJaw52T8yZYt8-ykL6UQ

Some seminars might be recorded and accessible for a limited time.

 

Upcoming Speakers

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Wubing Zhang is a Ph.D. student in Shirley Liu lab. He's research focuses on identifying novel therapeutic targets in cancer by machine learning modeling and integrative mining of high-throughput data.

December 2nd, 2021 

Host: Katherine Donovan

Wubing Zhang

Machine learning modeling of protein-intrinsic features predicts tractable targets of protein degraders

 
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Markus Queisser

High Throughput Approaches in Targeted Protein Degradation and PROTAC Synthesis

 

Markus got interested in protein degradation during his Master’s in Biochemistry at Free University Berlin, where he worked on understanding proteasome function. He further gained broad knowledge in respiratory diseases, inflammation and oncology while pursuing a Ph.D. in Biomedical Sciences at an international graduate programme at UGLC in Germany and Albert-Einstein College of Medicine. Markus then moved on to postdoctoral training at Northwestern University, where in collaboration with Noble Laureate Aaron Ciechanover, he characterised the regulation of ubiquitin ligase HOIL as a key mechanism of tumor adaptation to hypoxia. Prior to joining GSK, he specialized in ubiquitin-ligase recruitment at the Ludwig Institute for Cancer Research. Currently, Markus is a GSK Fellow and Scientific Director in the Protein Degradation Group at GSK, leading the technology team and multiple collaborations with biotechs and academia.

5 Selected Trainee Short Talks
 

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December 16th, 2021 

Host: Katherine Donovan

Chao Sun - Max Planck Institute for Brain Research

Subcellular Stoichiometry of Neuronal Proteasome Assembly

Dr. Chao Sun is an EMBO & HFSP postdoctoral fellow in Prof. Erin M. Schuman's lab at Max Planck Institute for Brain Research, Germany. His current research uses quantitative, multiplexed super-resolution microscopy to investigate the molecular resource supply for the vast population of synapses associated with a single neuron. He obtained his PhD with Prof. William R. Dichtel at Cornell University, US (now at Northwestern University, US), where he designed and manipulated molecular interactions to interface two-dimensional materials and molecular analogues for creating smart nano- materials and devices. His future research continues to focus on understanding and creating molecular systems that can 'think'.

Nan Bai - Amgen

Modeling CRL4A ligase complex to predict target protein ubiquitination induced by CRBN-recruiting PROTACs

I completed my PhD in Dr. John Karanicolas’ lab at Fox Chase Cancer Center (2012-2019), and my dissertation is about small molecule drug design. In my PhD lab, we use computational tools to study drug/target interactions and to further rationally design more effective drugs. During my PhD journey, one of my projects was focused on modeling PROTAC-mediated ternary complex formation. I am really attracted by this PROTAC concept and would like to explore more about this class of promising therapeutics. In 2020, I was very fortunate to join the Pharmacokinetics and Drug Metabolism (PKDM) group of Amgen as a postdoc and started to work on more PROTAC related projects. In my current work, we propose a structure-based computational approach to predict CRBN-based PROTAC induced target protein ubiquitination by integrating ternary complex and CRL4A ligase complex structural information.

Daniel Zaidman - University of Cambridge

PRosettaC: Rosetta Based Modeling of PROTAC Mediated Ternary Complexes

Daniel Zaidman started his studies in Tel-Aviv University, Israel, and finished a dual B.Sc. in mathematics and computer science. He then proceeded to do his master degree in bioinformatics in the lab of Prof. Haim Wolfson in Tel-Aviv University. In his masters he worked on designing inhibitory peptides for protein-protein interactions. He did his PhD in the lab of Dr. Nir London in the Weizmann Institute, where he worked on computational protocols for two uprising domains in drug discovery, namely, covalent inhibitors (such as Ibrutinib, Afatinib, etc.), and protein degraders (PROTACs). For both of these fields, he developed elegant protocols, combining novel ideas, end-to-end implementation and interactive web-servers to use the algorithms he developed. Currently he is pursuing his postdoc in the University of Cambridge, in the lab of Dr. Gonçalo Bernardes. Outside the university, his interests include foreign languages and Buddhist meditation.

Xiuxiu Lu - NCI/NIH

Structure-guided hRpn13-targeting bifunctional molecules as chemical probes of hRpn13 dysfunction
Dr. Xiuxiu Lu received her Ph. D. from the Shanghai Institute of Organic Chemistry, CAS for her structural studies that yielded a new model of DNA cytidine deaminase APOBEC3G with HIV single-stranded DNA in an active orientation. In 2014, Dr. Lu joined NCI/NIH as a postdoctoral fellow and was promoted to a research fellow in 2019. Dr. Lu solved the structure of ubiquitin receptor hRpn13 with its docking site at the proteasome by NMR and applied biochemical assays to provide novel insights into the potential of hRpn13 and its associated deubiquitinating enzyme Uch37 as anticancer targets. Dr. Lu has identified a chemical scaffold to target hRpn13 and found the lead compound XL5 to reduce cellular viability in cancer cell lines. By solving the structure of hRpn13 with XL5, Dr. Lu expanded the small molecule to include Proteolysis Targeting Chimeras (PROTAC) technology, yielding bifunctional molecules with greater efficacy in cellular assays.

Agatheeswaran Subramaniam - Lund University

UM171 promotes ex vivo expansion of hematopoietic stem cells by targeting the epigenetic modulator CoREST for degradation

Agatheeswaran Subramaniam is an associate researcher at Lund University and currently trying to establish his own research group. Agathees did his master’s in biotechnology (Bharathidasan university) PhD in leukemia biology (Utkal University) from India. Agathees is interested in developing targeted therapies for selectively eliminating cancer propagating cells. During his postdoctoral research, he unraveled the targeted protein degradation mechanism of a small molecule UM171 and actively developing a research program in this field.

 

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Eric Fischer

 
 
 

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.

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January 20th, 2022

TBD

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.

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February 3rd, 2022

Chemical biology studies of the thalidomide binding domain of cereblon

Host: Xiaoxi Liu

 

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.

4 Selected Trainee Short Talks
 

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February 17th, 2021 

Host: Katherine Donovan

Sistla Hemant - thinkMolecular Technologies

Structural Model of the ternary complex RNF114 - PROTAC - BRD4

I have completed my Masters in Physics from the Sri Sathya Sai Institute of Higher Learning, Puttaparthi, India. Currently, I am a Scientific Associate at thinkMolecular Technologies, a molecular simulations company based in Bengaluru. My 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 my 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.