Monday, September 21, 12:00-3:00 pm

SC3: Setting Up Effective RNAi Screens: From Design to Data to Validation -Detailed Agenda

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.

Instructors:

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., Group Lead, Functional Genomics, Genentech, Inc.

SC4: Phenotypic Screening and Chemical Probe Development -Detailed Agenda

This course is designed to expose participants to phenotypic drug discovery by showcasing various examples from literature and from NCATS. Each example will present the screening assay that was designed to discover small molecules that show a particular phenotypic response which is expected ameliorate the disease phenotype in the same or more advanced assays. We will also discuss the follow up work that was done to elucidate the mechanism of action and strategies used to de-convolute the molecular target. A portion of the course will also focus on the development of other chemical probes at NCATS using non-phenotypic assays that are able to demonstrate proof of concept in advanced cellular or animal models.

Instructor: Samarjit Patnaik, Ph.D., Research Scientist, Probe Development Center, NCATS, NIH

SC5: GPCR Structure-Based Drug Discovery -  Detailed Agenda

Recent breakthroughs in obtaining high resolution structures of G Protein-Coupled Receptors (GPCRs) are rapidly impacting the pharmaceutical industry. This course will review how newly elucidated GPCR crystal structures have informed our current understanding of GPCR function. Methodologies for GPCR crystallization will also be covered. The last third of the course will focus on the role of conformational dynamics in GPCR function and the structural biology techniques used for studying receptor dynamics, including the burgeoning field of nuclear magnetic resonance (NMR) applications.  

Instructors (all are currently or formerly from the Laboratory of Ray Stevens):

Matthew Eddy, Ph.D., Postdoctoral Fellow, Ray Stevens Laboratory, University of Southern California 

Wei Liu, Ph.D., Assistant Professor, Department of Chemistry and Biochemistry, Arizona State University 

Huixian Wu, Ph.D., Postdoctoral Associate, Stuart Schreiber Laboratory, Center for the Science of Therapeutics, The Broad Institute

Monday, September 21, 3:30-6:30 pm

SC6: Targeting of GPCRs with Monoclonal Antibodies -Detailed Agenda

While GPCRs (G protein-coupled receptors) are important therapeutic targets, it has been challenging to discover therapeutically relevant antibodies against them. This course will examine different steps along the anti-GPCR antibody discovery pathway and highlight various approaches to accomplishing each step. The topics to be covered include: 1) antibody discovery, including methods to generate antibodies and antigen preparation; 2) assays to measure antibody binding, such as an EC50 using cells expressing the GPCR; 3) in vitro assays to measure functional activity of the antibody, including antagonism (IC50) or agonism using chemotaxis, calcium, cAMP or other cell-based assays; and 4) review of promising GPCR targets and antibodies in the clinic.

Instructor: Barbara Swanson, Ph.D., Director, Research, Sorrento Therapeutics, Inc.

SC7: Setting Up Effective Functional Screens Using 3D Cell Cultures -Detailed Agenda

The course will provide an overview of the various 3D cell culture models available, their strengths and weaknesses, and where and how these models are being used, specifically for oncology research. The instructors will 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 low and high throughput screening experiments using 3D cell cultures in your lab. The challenges working with 3D cell cultures, from experimental design to data analysis will be discussed.

Instructors:

Arvind Rao, Ph.D., Assistant Professor, Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center

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

Madhu Lal-Nag, Ph.D., Team Leader, RNAi Screening, National Center for Advancing Translational Sciences, National Institutes of Health

SC8: Targeting Protein-Protein Interactions: Biophysical Approaches -Detailed Agenda

Protein-protein interactions (PPIs) represent a large but largely untapped class of biological targets covering virtually every therapeutic area. Despite several success stories, many researchers still consider PPIs to be “undruggable.” This course will provide attendees with an overview of how to discover small-molecule inhibitors of PPIs. Attendees will also learn about potential pitfalls and what not to do. Other topics covered will include how to evaluate the feasibility of PPIs, what biophysical techniques to use, and how fragment-based lead discovery can tackle particularly challenging PPIs.

Instructors:

Daniel A. Erlanson, Ph.D., Co-Founder and President, Carmot Therapeutics, Inc.

Edward R. Zartler, Ph.D., President & CSO, Quantum Tessera Consulting

Wednesday, September 23, 7:00-9:30 pm

SC9: Preclinical Animal Models for Ocular Indications  - Detailed Agenda

The goal of the workshop is to provide an introductory overview of current preclinical animal models for ocular indications. The presentations will focus on models for Age-Related Macular Degeneration, Ocular Inflammation and Glaucoma. An overview of the characteristics of different animal models, their pros and cons and potential uses will be discussed.

Instructors:

Andy Whitlock, Ph.D., Senior Director, Pre-Clinical Research & Development, Ophthalmology, Ora, Inc.

Goldis Malek, Ph.D., Associate Professor, Ophthalmology, Duke University School of Medicine

Maria B. Grant, M.D., FARVO, Professor, Ophthalmology, Eugene and Marilyn Glick Eye Institute, Indiana University

SC10: Introduction to Allosteric Modulators and Biased Ligands of GPCRs - Detailed Agenda

Allosteric modulators, pathway-biased ligands, and heteromer-biased ligands represent novel therapeutic approaches for achieving more selective actions with regards to G protein-coupled receptors (GPCRs). However the identification and characterization of such compounds can be challenging due in part to ‘context-dependent phenomena’. Aimed at scientists working on GPCRs this course will provide information on the identification and validation of allosteric, pathway-biased, and heteromer-biased drugs including emerging screening approaches, practical tips and tools for identification and validation, and the structural basis underlying such drugs.

Instructors:

Annette Gilchrist, Ph.D., Assistant Professor, Pharmaceutical Sciences, Midwestern University

Karen Gregory, Ph.D., Laboratory Head, Family C GPCR Division, Department of Drug Discovery Biology, (former post-doctoral fellow, Arthur Christopolous Lab), Monash University, Australia
Kevin Pfleger, Ph.D., Associate Professor, Molecular Endocrinology & Pharmacology, Harry Perkins Institute of Medical Research, University of Western Australia

SC11: Introduction to Targeted Covalent Inhibitors - Detailed Agenda

Covalent inhibitors of kinases have re-emerged as a drug design strategy due to more examples of their safety and efficacy in patients. Covalent inhibitors have the advantage of increased selectivity and longer action of duration but there are still important issues about their design and application that need to be better understood. This course will cover practical as well as theoretical issues that a medicinal chemist needs to keep in mind in developing covalent inhibitors.

Instructors:

Mark Schnute, Ph.D., Associate Research Fellow, Biotherapeutics Chemistry & Immunoscience Research, Pfizer Global R&D

Christoph Zapf, Ph.D., Principal Scientist, Worldwide Medicinal Chemistry, Pfizer Research Labs

SC14: A Primer to Gene Editing: Tools and Applications - Detailed Agenda

The course will help the novice understand the basics of how gene editing works, what tools are available for use and how those tools differ from each other. For the expert, this course will offer details on the CRISPR technology, how to set up CRISPR-based screens and complement it with existing RNAi-based screens using proper analysis and follow-up studies. The instructors will also cover the use of gene editing in drug discovery and disease modeling and best practices for design and workflows when working with other model systems, besides mammalian cells.

Instructors:

John Doench, Ph.D., Research Scientist, Broad Institute of Harvard and MIT

Michael Bassik, Ph.D., Assistant Professor, Department of Genetics, Stanford University

Mi Cai, Ph.D., Senior Scientist, Neuroscience & Pain Research Unit, Pfizer, Inc.

Stephanie Mohr, Ph.D., Department of Genetics, Harvard Medical School

SC15: Using Mechanistic Physiological Models in Drug Development: A Proven Quantitative Systems Pharmacology (QSP) Approach - Detailed Agenda

In this workshop, you will learn what mechanistic physiological QSP models are, how they are built, and how they can be applied. You will also be introduced to Rosa’s Model Qualification Method (MQM), a systematic approach for ensuring that a model is fit for the purpose for which it is intended. Concepts will be illustrated with examples and case studies. Interactive discussions will cover topics including:

• Criteria for mechanistic physiological QSP modeling projects to ensure impact
• Planning and scoping the model
• Incorporating multiple types of evidence and data sources
• Using “Virtual Patients” to explore uncertainty and variability
• Relevant qualitative and quantitative model testing
• Identifying opportunities for mechanistic physiological QSP modeling

Instructor: Christina Freidrich, Ph.D., Chief Engineer, Rosa & Co.

* Separate registration required for Short Courses