Matt Disney is a native of Baltimore and is currently Professor in the Department of Chemistry at Scripps Research on the Florida Campus. His laboratory works in the area of small molecule targeting of RNA. The lab seeks to answer fundamental questions regarding molecular recognition events between RNA folds and small molecules to study problems of biomedical importance. Indeed, they have developed a strategies to: (i) design structure-specific small molecules from the RNA’s sequence; (ii) synthesize drugs on-site in disease-affected cells to affect their function and to image them; (iii) study the biology of coding and non-coding RNAs, with a focus on incurable rare diseases and difficult-to-treat cancers; and (iv) interface RNAs with quality control machinery using small molecules and chimeras thereof to eliminate them from cells and animal models of disease. The lab’s research has garnered various awards including the Sackler Prize in the Physical Sciences, Barry Cohen Award in Medicinal Chemistry, NIH Director’s Pioneer Award, the Tetrahedron Young Investigator Award, the Eli Lily Award in Biological Chemistry, the David W. Robertson Award in Medicinal Chemistry, and others.
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.
How Biophysics can Advance a Small Molecule Neuroscience Portfolio
Dr. Laura Silvian, Sr. Director, leads the innovative Physical Biochemistry and Molecular Design group within the Biotherapeutic and Medicinal Sciences department at Biogen in Cambridge, MA. We use structure-based, rational drug design and biophysical assessments to improve potency, selectivity or developability of therapeutics for the treatment of neurodegenerative diseases. We influence program team decisions in engineering different therapeutic modalities --biologics, small molecule, and gene therapy-- using cutting-edge techniques in structural biology, biophysical methods, and protein science.
In past years we have embraced several new technologies including:
• assembly of recombinant protein complexes including membrane proteins and RNA/protein complexes,
• small molecule compound binding measurements,
• Cryo-EM in addition to longstanding capabilities in X-ray Crystallography, and NMR for structure solution,
• and molecular design strategies for improved biologics efficacy and developability.
Laura is an inventor or coauthor on more than 40 publications and 5 patents on protein and RNA targets. She served as chair of the Industrial Scientific Interest group at the ACA, reviewed grants for Michael J Fox Foundation, and has chaired sessions at Discovery on Target conferences.
Session 1: Emerging Technologies - New Biophysical Approaches for Measuring Molecular Interactions
Title of talk to be announced (virtual presentation)
Dr Jonathan BROOKS
PFIZER, Cambridge, United States
Title of talk to be announced
Dr Pedro SERRANO NAVARRO
TAKEDA CALIFORNIA, INC., San Diego, United States
Session 2: Covalent Drug Discovery
In-cell Covalent Inhibitors Discovery
Dr Brent MARTIN
SCORPION THERAPEUTICS, Boston, United States Read more
Dr Brent MARTIN
Brent Martin received his Ph.D. in Pharmacology at the University of California in San Diego followed by postdoctoral studies at the Scripps Research Institute developing new strategies for activity-based profiling, high-throughput screening, and chemical proteomics. As faculty member at the University of Michigan in Ann Arbor, he continued expanding the scope of activity-based profiling methods, while also establishing new bioconjugation reactions to detect and profile protein lipidation, redox modifications, and cysteine occupancy. Brent is the recipient of the NCI Howard Temin K99/R00 award in Cancer Research, the NIH Director’s New Innovator Award, and the NIGMS MIRA Established Investigator Award. He later led the Chemical Biology at Janssen and is currently Vice President and Head of Chemical Biology at Scorpion Therapeutics.
Developing Covalent Small Molecules for the Protein Targets from Kinase to Transcription Factor
Dr. Zhang is a senior scientist at Cancer Institute of Stanford. Dr. Zhang is an experienced medicinal chemist and chemical biologist. Dr. Zhang leads and supervises drug discovery projects with the targets of kinases and transcription regulators. His research focuses on the discovery of covalent modality and protein degradation. He has led the discoveries of covalent inhibitor of CDK7, CDK12/13, JNK, PIP4K, MKK4, Src and TEAD and degrader molecules for CDK12, CDK4/6, FGFR1/2, CDK2/5 et al. Under his leadership, Dr. Zhang has contributed several prototype chemical leads for further drug development including THZ1. Dr. Zhang was also a chemistry group leader at the Center of Protein Degradation (CPD) of Dana-Farber from 2018 to 2021. Dr. Zhang received his Ph.D in chemistry from USTC (China) in 2004.
Session 3: Hybrid Methods and Technique Combinations
Integration of Biophysics and Simulation to Drive Drug Discovery
Dr Holly SOUTTER
BROAD INSTITUTE, Cambridge, United States Read more
Dr Holly SOUTTER
Holly Soutter is Director of Biochemistry and Biophysics within the Center for the Development of Therapeutics (CDoT) at the Broad Institute of MIT and Harvard. Her research group supports projects across multiple therapeutic areas to identify, validate, and mechanistically characterize potential small molecule therapeutics. Her team has expertise in multiple techniques including SPR, NMR, mass spectrometry, enzymology, and many others. Dr. Soutter has over 15 years of experience in the pharmaceutical and biotech sectors. She has made key contributions to multiple clinical candidates, and has co-authored more than 20 scientific publications. She received her B.A. in Chemistry from Hunter College, and her M.A. and Ph.D. in Chemistry from Clark University.
Session 4: Biophysical Assays for PROTACs and Molecular Glues
Structural and Biophysical Studies of Protein Degrader Ternary Complexes
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.
An Integrated Biophysical Approach to Discover Ligands for a Novel E3 Ligase
Dr Nichole O'CONNELL
KYMERA THERAPEUTICS, Watertown, United States Read more
Dr Nichole O'CONNELL
Nichole O’Connell received her PhD in Biochemistry and Molecular Biophysics from Columbia University where she studied protein dynamics by NMR. Following her PhD, she took a moved to Brown University as a postdoctoral student in the lab of Wolfgang Peti, studying phosphatase structure and function. Next, she moved to AstraZeneca for an industrial postdoc. In 2013, she transitioned to Senior Scientist in the Structure and Biophysics group at AstraZeneca. Nichole then ventured into biotech at Nurix and Cedilla Therapeutics before joining Kymera Therapeutics in 2019 where she is presently Associate Director, Head of Platform Discovery.
Session 5: Small Molecules Targeting RNA / Understanding Small-Molecule Selectivity Towards RNA
Title of talk to be announced
Dr Elena MENICHELLI
ARRAKIS THERAPEUTICS, Waltham, United States
Exploring the Undiscovered Country of RNA as a Drug target—Finding Bioactive Ligands against XIST RNA with Affinity-selection MS Screening
Dr Elliott B. NICKBARG
MERCK RESEARCH LABORATORIES, Boston, United States Read more
Dr Elliott B. NICKBARG
Elliott Nickbarg PhD is a Principal Scientist in the Quantitative Biosciences Department at Merck Research Laboratories in Boston MA. He received a bachelor’s of science degree from the University of Chicago, a doctorate in Chemistry from Harvard University and did postdoctoral work at the University of Pennsylvania.
Since then, he has worked at both small biotechnology and large phamaceutical organizations, starting with Genetics Institute, Inc. of Cambridge MA (later part of Wyeth Pharmaceuticals) working on development and applications of proteomics technology. He later joined Neogenesis Pharmaceuticals and helped develop affinity-selection mass spectrometry and its applications and has continued to apply mass spectrometry analysis for protein, RNA and small molecules, As part of these varied efforts, he has a total of almost three decades of experience in both small and large molecule drug discovery.