Monday, September 23 | 12:00 – 3:00 pm
SC1: New Class of Kinase Inhibitors: Covalent Modifiers
Interest in covalent kinase inhibitors as potential drug candidates is steadily increasing and there is a growing body of data showing both efficacy and safety in patients. Covalent inhibitors offer a means of obtaining optimal target engagement with excellent selectivity and a prolonged duration of action. This workshop will cover practical and theoretical considerations for designing selective covalent kinase inhibitors, as well as considerations for testing schemes to examine on- and off-target activities.
Alan Corin, Ph.D., Senior Director, Biochemistry and Molecular Pharmacology, Celgene Avilomics Research
Eric Schwartz, Ph.D., Senior Director, Chemistry, Celgene Avilomics Research
SC2: Practical Aspects of Structure-Based Drug Discovery with GPCRs - Detailed Agenda
This course will explore the changes in rational drug design approaches for GPCRs in light of the new structural knowledge now available from the many new GPCR crystal structures. Questions such as quality of crystal data, expected throughput and turnaround times and impact on modeling activities will be explored.
Michael Hanson, Ph.D., Director, Structural Biology, Receptos
Christopher Tate, Ph.D., Professor, Laboratory of Molecular Biology, MRC, United Kingdom
SC3: Biochemical and Structure-Based Approaches to Epigenetic Drug Discovery
An increasing amount of chemically tractable compounds modulating various epigenetic targets are now in pre-clinical and clinical development. However, obtaining potent, highly-selective and cell-active inhibitors, requires skillful utilization of varied assays and screening methods such as high-throughput screening (HTS), focused screening, knowledge-based and fragment-based approaches, to efficiently navigate lead discovery of epigenetic targets. This workshop is designed as a tutorial by discovery leaders to discuss tools and techniques, application specific methods, and best practices for the development of chemically tractable epigenetic inhibitors.
David Sheppard, Ph.D., Director, Computational Chemistry, BioFocus Zhaohui Sunny Zhou, Ph.D., Faculty Fellow, Barnett Institute of Chemical and Biological Analysis; Associate Professor, Department of Chemistry and Chemical Biology, Northeastern University
Additional Instructors to be Announced
Monday, September 23 | 3:30 – 6:30 pm
SC4: Allosteric Modulators of GPCRs
Allosteric modulators represent a novel paradigm to therapeutically target G-protein-coupled receptors (GPCRs). However, their identification and characterization using standard functional assays remain elusive due to the‘context-dependent phenomena’. This course will discuss important aspects of hit identification and validation of allosteric modulators in GPCR research activity.
Corey Hopkins, Ph.D., Research Assistant Professor, Pharmacology, Vanderbilt University
Debra Kendall, Ph.D., Distinguished Professor & Department Head, Pharmaceutical Sciences, University of Connecticut
Stephan Schann, Ph.D., Head, Research, Domain Therapeutics SA
SC5: Advancing Tools and Technologies for Fragment-Based Design - Detailed Agenda
This course aims to introduce the fundamentals of Fragment-based Lead Discovery (FBLD) to attendees. The first section will focus on the concepts of using fragments for hit generation. Special emphasis will be placed on practical pitfalls and the many ways to advance fragments to leads and drugs. The second part of the course will discuss the variety of fragment screening methods and when they are best applied. The composition of fragment libraries will also be discussed in detail. The attendees should come away from this course with a solid understanding of what FBLD is and how to apply it.
Daniel A. Erlanson, Ph.D., Co-Founder, Carmot Therapeutics, Inc.
Edward R. Zartler, Ph.D., President & CSO, Quantum Tessera Consulting
SC6: Setting Up Effective RNAi Screens: Getting From Design to Data
The course is designed to provide in-depth information on how to go about setting up RNAi screening experiments and how to design assays for getting optimal results. The challenges working with siRNAs and shRNAs and the delivery reagents needed to get them into the appropriate cells and tissues will be discussed. The instructors will also provide their input on best practices for the execution of experiments and interpretation of results when dealing with complex biology and informatics.
Caroline Shamu, Ph.D., Director, ICCB-Longwood Screening Facility, Harvard Medical School
Eugen Buehler, Ph.D., Group Leader, Informatics, National Center for Advancing Translational Sciences, National Institutes of Health
John Doench, Ph.D., Research Scientist, Broad Institute of Harvard and MIT
Scott Martin, Ph.D., Team Leader, RNAi Screening, NIH Chemical Genomics Center, NIH Center for Translational Therapeutics, National Institutes for Health
SC7: Production and Presentation of Integral Membrane Proteins for Antibody Discovery
Small molecule pharmaceuticals can exhibit remarkable target specificity. Nevertheless, the exquisite selectivity towards the desired subtype of an ion channel or GPCR is often elusive, resulting in undesirable effects on closely related variants. Antibodies hold promise of even greater specificity, and are proven to be effective therapeutics targeting certain membrane proteins. Yet none of the current targets for approved antibodies is either a GPCR or an ion channel. A main reason for this is the difficulty involved in the effective presentation of integral membrane proteins for antibody generation-selection. This workshop surveys the latest methods and insights to generate useful antibodies to integral membrane proteins, and to favor the desired binding interactions for the therapeutic mechanism or diagnostic purpose.
Instructor: David Bramhill, Ph.D., Principal, Bramhill Biological Consulting, LLC
SC8: Characterization and Quantification of Histone Modifications
Until recently, standardized high-throughput methods for characterizing and quantifying post-translational histone modifications have been challenging. Now, with the application of advanced methods utilizing modification-specific antibodies and high resolution mass spectrometry, various strategies have been developed for precise in vivo monitoring and profiling of histones, their variants, reader proteins, the combinatorial histone code, and the overarching chromatin landscape in multiple cellular states. This workshop is designed to provide a tutorial on utilizing what is becoming the gold standard for histone post-translational modification analysis.
Alan Tackett, Ph.D., Associate Professor, Director UAMS Proteomics Facility, University of Arkansas for Medical Sciences
Sean Taverna, Ph.D., Assistant professor, Pharmacology & Molecular Sciences, IBBS Center for Epigenetics, Johns Hopkins University School of Medicine
Yingming Zhao, Ph.D., Professor, The Ben May Department for Cancer Research, University of Chicago
Wednesday, September 25 | 6:45 – 9:30 pm • Dinner will be provided
SC9: Setting Up Effective Functional Screens Using 3D Cell Cultures
The course is designed to provide in-depth information on how to go about setting up low and high-throughput screening experiments using 3D cell cultures. The challenges working with 3D cell cultures, from experimental design to data analysis will be discussed. The instructors will also share their experiences on how they tested and evaluated various cell culture reagents and growth matrices, what worked and what didn’t and what you need to consider when setting up similar screens in your lab.
Geoffrey A. Bartholomeusz, Ph.D., Assistant Professor and Director, siRNA Core Facility, Department of Experimental Therapeutics, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center
Lesley Mathews, Ph.D., Research Scientist, Biomolecular Screening and Profiling/Probe Development Group, National Center for Advancing Translational Sciences, NIH
Additional Instructors to be Announced
SC10: Tools for Detection and Utilization of Epigenetic Markers
Evaluation of Potential Ex Vivo Biomarkers and Molecular Imaging to Determine Early Pharmacodynamic Efficacy of HDAC Inhibitors
Pamela Munster, M.D., Associate Professor, Department of Medicine, University of California San Francisco
Development of Methods to Assess Epigenetic Markers of Phenotypic Heterogeneity Using Physiologically Relevant Cell Culture Models
Sophie Lelièvre, D.V.M., LL.M., Ph.D., Associate Professor, Department of Basic Medical Sciences; Associate Director, Discovery Groups, NCI-Designated Purdue Center for Cancer Research, Purdue University
An Integrated PTM-Technology Platform for Biomarker Discovery and Hard-to-make Reagents
Jack Zhongyi Cheng, Ph.D., CEO, PTM Biolabs, Inc
*Separate Registration Required for Short Courses