Loading…
Ono Pharma Foundation Symposium has ended
BY INVITATION ONLY - REGISTER BY JUNE 21, 2019.

Sign up or log in to bookmark your favorites and sync them to your phone or calendar.

Monday, July 1
 

10:00am EDT

Registration
Monday July 1, 2019 10:00am - 10:30am EDT
Prefunction Area - Abigail Adams Ballroom
  All Group
  • surveys y

10:30am EDT

Welcome
Speakers
avatar for Tetsuya Sugiyama

Tetsuya Sugiyama

Director & President, Ono Pharma Foundation
Mr. Sugiyama founded Ono Pharma Foundation and has been the director and president since the establishment in 2017. The Foundation was formed in DE as a 501(c)(3) entity, which administrates the Ono Pharma Breakthrough Science Initiative Awards Program to support scientists having... Read More →


Monday July 1, 2019 10:30am - 10:35am EDT
Abigail Adams Salon A/B
  All Group
  • surveys y

10:35am EDT

Opening Remarks
Speakers
avatar for Stuart Schreiber, PhD

Stuart Schreiber, PhD

Professor, Harvard University
Stuart Schreiber is co-Founder of the Broad Institute, Howard Hughes Medical Institute Investigator, Morris Loeb Professor of Chemistry and Chemical Biology at Harvard University, and has been a member of the National Academy of Sciences since 1995. Dr. Schreiber’s lab integrates... Read More →


Monday July 1, 2019 10:35am - 10:45am EDT
Abigail Adams Salon A/B
  All Group
  • surveys y

10:45am EDT

Attenuating Oncogenic Transcription with Small Molecules
The Koehler Lab uses chemical biology approaches to investigate deregulated transcriptional programs in cancer. We are taking on the challenge of developing chemical probes that either directly target oncogenic transcription factors (TFs), currently deemed ‘undruggable,’ or that target ‘nearest neighbor’ proteins that indirectly modulate TF function through mechanisms involving alterations in protein production or protein stability. The probes can be used to further understand the functions surrounding any given transcriptional regulator, clarify their relevance as therapeutic targets, and enable credentialing of mechanisms for targeting by small-molecule drugs. As an example of our approach, probes that impact the MYC oncogene, which encodes a master regulator and is causally associated with most human malignancies, will be described.  The lab identified a unique small molecule, KI-MS2-008, that binds to MAX, inhibits MYC-driven transcription, and stabilizes the MAX homodimer in vitroand in cells while reducing MYC protein levels. The compound displays anti-tumor activities in vitro and in vivo using engineered and non-engineered systems.

Speakers
avatar for Angela Koehler, PhD

Angela Koehler, PhD

Associate Professor, Biological Engineering, MIT
Angela Koehler is the Goldblith Career Development Professor in Applied Biology in the Department of Biological Engineering at MIT and an intramural member of the David H. Koch Institute for Integrative Cancer Research at MIT. She is also an Institute Member of the Broad Institute... Read More →


Monday July 1, 2019 10:45am - 11:15am EDT
Abigail Adams Salon A/B

11:15am EDT

Turning up the Volume: Augmenting Natural 14-3-3/phosphoprotein Interactions
Scaffolding proteins act as protein-interaction hubs, but have been considered nearly un-targetable by drugs and chemical probes.  The seven human isoforms of 14-3-3 are ubiquitous mediators of kinase pathways, modulating the function, stability, and subcellular localization of phosphorylated client proteins. In collaboration with the Ottmann lab (Eindhoven University of Technology), we are using fragment-based ligand discovery and structure-guided design, to systematically develop molecules that stabilize specific 14-3-3/phosphopeptide complexes.  To date, we have discovered stabilizing fragments for five important cancer targets, and are designing more potent covalent and noncovalent compounds for testing in cells.  Our long-term goal is to use these molecular probes to dissect the 14-3-3 PPI network and validate targets for therapeutic intervention.


Speakers
avatar for Michelle Arkin, PhD

Michelle Arkin, PhD

Professor, Pharmaceutical Chemistry, University of California, San Francisco
Michelle Arkin is a chemical biologist/biochemist interested in developing first-in-class modulators of really challenging targets, such as protein-protein interactions, transcription factors, and aggregating proteins. Her lab works on protein-protein interaction networks in cancer... Read More →


Monday July 1, 2019 11:15am - 11:45am EDT
Abigail Adams Salon A/B

11:45am EDT

Chemoproteomic technology for the direct identification of druggable protein nucleophiles
Speakers
avatar for Jack Taunton, PhD

Jack Taunton, PhD

Professor, Cellular Molecular Pharmacology, University of California, San Francisco


Monday July 1, 2019 11:45am - 12:00pm EDT
Abigail Adams Salon A/B

12:00pm EDT

Using cell-based profiling to develop predictive signatures of toxic and intractable small molecules
Small-molecule profiling methods, such as cell painting gene expression analysis, can be very useful for uncovering mechanism of action for novel compounds and for identifying compound similarities. In this project, we aim to use such small-molecule profiling methods to develop signatures of bioactivity. Here, we have applied this approach to develop predictive signatures of drug candidates with in vivo toxicity, and of nuisance compounds that are often false-positives in high-throughput screening. In particular, we tested a set of ~400 thiol-reactive compounds in cell painting, and found that these compounds comprise an independent cluster by principal component analysis. We anticipate that this approach will provide an rapid and efficient route for uncovering complex phenotypes induced by small molecules.

Speakers
avatar for Bridget Wagner, PhD

Bridget Wagner, PhD

Institute Scientist, Broad Institute
Bridget Wagner is an Institute Scientist in the Chemical Biology & Therapeutics Science (CBTS) Program at the Broad Institute. Her group focuses on the discovery of small molecules that beneficially impact pancreatic beta-cell biology (proliferation, survival, insulin secretion... Read More →


Monday July 1, 2019 12:00pm - 12:15pm EDT
Abigail Adams Salon A/B

12:15pm EDT

Discovery of small molecule binding site hotspots in the global proteome
All biological processes are governed by chemical signals relayed through protein networks. These small molecule signals can inhibit, enhance, or impart new functions to proteins through direct associations to allosteric regulatory hotspots on a protein that drive alteration of the broader proteomic network.  To discover allosteric hotspots in the global proteome, we developed a chemical proteomics platform termed small molecule interactome mapping by photo-affinity labeling (SIM-PAL).  SIM-PAL uses a small molecule carrying a photo-affinity label to capture molecular interactions within the global proteome.  After treatment of live cells with the small molecule, the resulting interactions are captured by photochemical conjugation.  The small molecule-conjugated proteome is tagged with a cleavable biotin azide probe by copper-mediated azide–alkyne cycloaddition (CuAAC) for affinity enrichment and isotope-recoding.  The enriched proteins are identified by proteomics and the exact binding sites are mapped by isotope-targeted mass spectrometry (MS). Isotope-targeted MS enables the selection of small molecule-linked peptides against a background of unlabeled peptides for high-confidence identification of the underlying molecular structure.  SIM-PAL combines phenotypic cellular assays with high-resolution structural measurement of where and when a small molecule is binding throughout the whole proteome using the discovery power of MS.  Applications of SIM-PAL to bioactive small molecules and the structural implications of binding site hotspots from photo-affinity labeling chemistry will be described.

Speakers
avatar for Christina Woo, PhD

Christina Woo, PhD

Assistant Professor, Harvard University
Christina M. Woo is an assistant professor in the Department of Chemistry and Chemical Biology at Harvard University, and an affiliate member of the Broad Institute. She obtained a BA in Chemistry from Wellesley College (2008), and conducted undergraduate research in the laboratory... Read More →


Monday July 1, 2019 12:15pm - 12:30pm EDT
Abigail Adams Salon A/B

12:30pm EDT

Lunch
Monday July 1, 2019 12:30pm - 1:15pm EDT
Abigail Adams Salon C
  All Group
  • surveys y

1:15pm EDT

Expanding the Scope of Base Editing
Through a combination of protein engineering and protein evolution, we recently developed two classes of base editors (CBE and ABE) that together enable all four types of transition mutations (C to T, T to C, A to G, and G to A) to be efficiently and cleanly installed or corrected at target positions in genomic DNA without making double-stranded DNA breaks. The four transition mutations collectively account for most known human pathogenic point mutations. Recently we have expanded the scope of base editing by enhancing its efficiency, product purity, targeting scope, and DNA specificity. By optimizing base editor expression, we developed “max” versions of cytosine and adenine base editors with greatly increase editing efficiency in mammalian cells.  To improve the targeting scope of base editing, we used our phage-assisted continuous evolution (PACE) system to rapidly evolve Cas9 and base editor variants with broadened PAM compatibility, higher DNA specificity, and enhanced editing capabilities. Finally, we are developing new base editor systems that operate on cellular RNA.

Speakers
avatar for David R. Liu, PhD

David R. Liu, PhD

Richard Merkin Professor, Director of the Merkin Institute of Transformative Technologies in Healthcare, and Vice-Chair, Harvard University
David R. Liu is the Richard Merkin Professor, Director of the Merkin Institute of Transformative Technologies in Healthcare, and Vice-Chair of the Faculty at the Broad Institute of Harvard and MIT; Thomas Dudley Cabot Professor of the Natural Sciences and Professor of Chemistry and... Read More →


Monday July 1, 2019 1:15pm - 1:45pm EDT
Abigail Adams Salon A/B

1:45pm EDT

Chemical biology of anti-cancer innate immunity
Speakers
avatar for Lingyin Li

Lingyin Li

Assistant Professor of Biochemistry, Stanford University
Dr. Li is an assistant professor in the Biochemistry Department and ChEM-H Institute at Stanford since 2015. Her lab works on understanding biochemical mechanisms of innate immunity and harnessing it to treat cancer. She majored in chemistry at University of Science and Technology... Read More →


Monday July 1, 2019 1:45pm - 2:15pm EDT
Abigail Adams Salon A/B

2:15pm EDT

Selective Neuronal Delivery of ASOs Targeting APP
Speakers
avatar for William Mobley, PhD

William Mobley, PhD

Professor, University of California, San Diego
Dr. Mobley is Associate Dean of Neurosciences Initiatives and Distinguished Professor of Neurosciences at UC San Diego. He serves as Executive Director of UCSD's Down Syndrome Center for Research and Treatment, and holds the Florence Riford Chair of Alzheimer Disease Research. He... Read More →


Monday July 1, 2019 2:15pm - 2:30pm EDT
Abigail Adams Salon A/B

2:30pm EDT

How druggable is the transcriptome? Finding small molecule binding sites in RNA.
Despite our increasing appreciation of non-coding RNA function, RNA has been conspicuously underrepresented in small-molecule drug development efforts until recently. Now it is clear binding pockets on RNA can make good drug targets, yet the properties and principles of small molecule binding sites on RNA remain poorly defined. I will discuss the challenges of defining small-molecule binding sites across the transcriptome and new approaches to address these challenges.

Speakers
avatar for Matthew Simon, PhD

Matthew Simon, PhD

Associate Professor of Molecular Biophysics and Biochemistry, Yale University
Matt grew up in Ann Arbor, MI and received his Ph.D. in Chemistry from UC Berkeley. He commuted between Berkeley and UCSF, working with Kevan Shokat developing chemical methods to make synthetic chromatin substrates to study the biochemistry of epigenetics. He continued this work... Read More →


Monday July 1, 2019 2:30pm - 2:45pm EDT
Abigail Adams Salon A/B

2:45pm EDT

Healthy Brains and Mixed Backbones
The central nervous system (CNS) is a very promising tissue for the use of antisense oligonucleotides (ASOs), with one drug approved and six others in clinical trials. Nevertheless, we have found that the administration of ASOs to the CNS often causes acute toxicity.  In this talk, we use a novel assay to quantify ASO-induced acute toxicity, explore its mechanism, and identify both modification and formulation approaches that provide ASOs with improved therapeutic index in both small (mouse) and large (sheep) brains. 

Speakers
avatar for Jonathan Watts, PhD

Jonathan Watts, PhD

Associate Professor, RNA Therapeutics Institute at UMass Medical School
Nucleic acid chemistry and chemical biology; gene silencing, gene activation and genome editing


Monday July 1, 2019 2:45pm - 3:00pm EDT
Abigail Adams Salon A/B

3:00pm EDT

Poster Session & Break
20 posters will be presented in this interactive session. Post-docs, students and young scientists working in the fields of Chemical Biology Research and Oligonucleotide Medicine Research are invited. Please join us and use this opportunity to learn the advanced research and partake in discussions and networking with other attendees.
  1. Mierav Segal, BIDMC, Hydrophobically-modified let-7b miRNA conjugate enhances biodistribution to NSCLC and downregulates HMGA2 in vivo
  2. Wenjian Wang, Boston College, Protein surface recognition via chemically enhanced phage display
  3. Chao Liu, Boston College, Facile Sulfation of Carbohydrates and Peptides via Electron-Deficient Aryl Sulfate Diesters
  4. Daniel Bak, Boston College, Chemoproteomic Studies of the Iron-Sulfur Proteome
  5. Allyson Freedy, Harvard University, CRISPR-suppressor scanning reveals a non-enzymatic role of LSD1 in AML
  6. Kevin Ngan, Harvard University, Activity-based CRISPR-scanning of DNMT1 and UHRF1
  7. Yuka Amako, Harvard University, Enantiospecific binding site hotspot mapping of the immunomodulatory drugs
  8. David Miyamoto, Harvard University, Discovery of functional metabolite–protein binding site hotspots
  9. Robert M. Wilson, MIT, Chemical Screening Against the Pluripotency Factor LIN28
  10. Andrew Chen, MIT, Discovery and Characterization of a Small Molecule that Modulates c-Myc Mediated Transcription via Max Homodimer Stabilization
  11. Jonnell Small, Broad Institute, Investigating the Mechanisms of Beta-Cell Glucolipotoxicity Protective Small Molecules
  12. Jameson Dahlin, Broad Institute, Unbiased cellular morphology profiling for the evaluation of cellular toxicities and assay interferences
  13. Luke Koblan, Broad Institute, In vivo Correction of Pathogenic SNPs with Optimized Base Editors
  14. Tony Huang, Broad Institute, Circularly permuted and PAM-modified base editors with broadened targeting scope
  15. Christopher Gerry, Broad Institute, Incorporating Topographically Complex Small Molecules into DNA-Encoded Libraries
  16. Matthias Westphal, Broad Institute, Harnessing unusual reactivity for DNA-encoded library synthesis
  17. Min Wook Shin, University of Massachusetts, Distribution and Effect of Intratracheally Administered Antisense Oligonucleotides on Different Lung Cell Populations
  18. Juta Kobayshi, Ono Pharmaceutical, NMR-based analysis of protein-ligand interactions towards drug discovery
  19. Takayuki Inukai, Ono Pharmaceutical, Targeting Dynamic ATP-Binding Site Features Allows Discrimination between Highly Homologous Protein Kinases
  20. Kenji Sasaki, Ono Pharmaceutical, Ligand and Target Discovery by Fragment-Based Screening in Human Cells

Monday July 1, 2019 3:00pm - 4:30pm EDT
Hutchinson
  All Group
  • surveys y

4:30pm EDT

Community Discussion
Join us for this interactive and exciting session in which all attendees will have the opportunity to engage and partake in discussions. Topics led by the moderator, will include drug modalities, approach from undruggable to druggable, biomarkers and transnational work from basic science.


Speakers
avatar for Stuart Schreiber, PhD

Stuart Schreiber, PhD

Professor, Harvard University
Stuart Schreiber is co-Founder of the Broad Institute, Howard Hughes Medical Institute Investigator, Morris Loeb Professor of Chemistry and Chemical Biology at Harvard University, and has been a member of the National Academy of Sciences since 1995. Dr. Schreiber’s lab integrates... Read More →


Monday July 1, 2019 4:30pm - 5:30pm EDT
Abigail Adams Salon A/B

5:30pm EDT

Closing Remarks
Speakers
avatar for Tetsuya Sugiyama

Tetsuya Sugiyama

Director & President, Ono Pharma Foundation
Mr. Sugiyama founded Ono Pharma Foundation and has been the director and president since the establishment in 2017. The Foundation was formed in DE as a 501(c)(3) entity, which administrates the Ono Pharma Breakthrough Science Initiative Awards Program to support scientists having... Read More →


Monday July 1, 2019 5:30pm - 5:40pm EDT
Abigail Adams Salon A/B
  All Group
  • surveys y

5:45pm EDT

Networking Reception
Monday July 1, 2019 5:45pm - 7:45pm EDT
Abigail Adams Salon C
  All Group
  • surveys y