Target Identification Strategies


Cambridge Healthtech Institute 第1届
标靶识别策略
新平台、高度策略、优异研究成果

第15届Discovery on Target其中一环

本会议以标靶识别策略为主题,主要专家将齐聚一堂讨论该领域重要成果。本会议目的为提供来自全球各国的专家一个能够建立人脉、分享新想法、讨论可能实现标靶识别的新方法的场合。

Final Agenda


RECOMMENDED ALL ACCESS PACKAGE:

· September 25 Symposium: Constrained Peptides and Macrocyclics

· September 25 Short Course: Applications of Functional Screening Using CRISPR and RNAi

· September 26-27 Conference: CRISPR for Disease Modeling and Target Discovery

· September 27-28 Conference: Target Identification Strategies

· September 27 Short Course: Practical Phenotypic Screening

· September 28-29 Symposium: Tackling Rare Diseases


Wednesday, September 27

11:50 am Conference Registration Open

12:20 pm Plenary Keynote Program

(click here for details)

2:00 Refreshment Break in the Exhibit Hall with Poster Viewing

Using CRISPR and RNAi Screens for Target Identification & Validation

2:45 Welcome Remarks

Tanuja Koppal, Ph.D., Conference Director, Cambridge Healthtech Institute

2:50 Chairperson's Opening Remarks

John Feder, Ph.D., Associate Director of Genome Biology and Emerging Technologies, Department of Genetically Defined Diseases and Genomics, Bristol-Myers Squibb

2:55 Development and Optimization of CRISPR Gene Editing for Drug Discovery Applications

John Feder, Ph.D., Associate Director of Genome Biology and Emerging Technologies, Department of Genetically Defined Diseases and Genomics, Bristol-Myers Squibb

The integration of CRISPR genome engineering into the drug discovery process is well underway. Examples will be presented as to how CRISPR is being used to address many of the issues that have traditionally stymied drug development. Data and learnings will also be shared from our recent efforts to improve the methods for CRISPR-based homology directed repair gene editing.

3:25 High-Throughput CRISPR-Based Approaches to Cancer Target Identification

Stephanie Mohr, Ph.D., Lecturer, Genetics & Director, Drosophila RNAi Screening Center at Harvard Medical School

Drosophila research has pioneered advances in cancer-related research, including identification of hedgehog and hippo signaling pathways. A new generation of fly studies seamlessly moves from work in the fly to mammalian systems. We use CRISPR knockout and activation to model cancers and identify new therapeutic strategies. Through this work, we are able to identify synthetic lethal interactions that can be recapitulated in mammalian cancer cells.

3:55 Ultra-Sensitive Targeted RNA Expression Profiling: DriverMap Human Genome-Wide Gene Expression Profiling Assay

Paul Diehl, Ph.D., COO, Cellecta

The DriverMap assay's unparalleled specificity and sensitivity results in greatly enhanced detection of low- and medium- abundance mRNA transcripts as well as an improved cost-effectiveness for high-throughput research applications.

4:10 Sponsored Presentation (Opportunity Available)

4:25 Refreshment Break in the Exhibit Hall with Poster Viewing

5:00 Expanding Mechanisms and Therapeutic Targets for Neurodegenerative Disease

Aaron Gitler, Ph.D., Associate Professor, Department of Genetics, Stanford University

5:30 CRISPR vs. RNA Interference for the Discovery of Cancer Genetic Dependencies

Jason Sheltzer, Ph.D., Principal Investigator, Cold Spring Harbor Laboratory

To date, many genetic dependencies in cancer have been discovered using RNAi. While RNAi is modular, reversible, and generally insensitive to gene copy number, it is also susceptible to off-target interactions. In several instances, CRISPR/Cas9-mutagenesis fails to recapitulate genetic dependencies previously discovered using RNAi. For example, MELK a putative breast cancer dependency identified via RNAi screening can be mutated with CRISPR without any apparent fitness defect. We discuss the advantages and disadvantages of both in the light of these results.

6:00 RNAi Screens for Identifying Kinases That Mediate Tumor Resistance to T Cell Attack

Tillmann Michels, Ph.D., Head of Research Group Immune Checkpoint Inhibitors, Laboratory of Prof. Philipp Beckhove, Regensburg Center for Interventional Immunology

Effector molecules of T cell attack against tumors not only fail to induce tumor death at low concentrations (or effector-to-target ratios) but induce tumor proliferation. Using high throughput RNAi screens, we identified kinases that shift effector molecule induced signaling form apoptosis to survival. These kinases are optimal targets to increase the clinical benefits of immunotherapy.

6:30 Close of Day

6:30 Dinner Short Course Registration

Click here for details on short courses offered.

Thursday, September 28

7:30 am Registration Open

8:00 Interactive Breakout Discussion Groups with Continental Breakfast

Grab a cup of coffee and join a breakout discussion group. These are informal, moderated discussions with brainstorming and interactive problem solving, allowing participants from diverse backgrounds to exchange ideas and experiences and develop future collaborations around a focused topic. Details on the topics and moderators are available on the conference website.

Phenotypic Screening & Chemical Biology Tools

9:00 Chairperson's Remarks

Gregory A. Michaud, Ph.D., Chemical Biology and Therapeutics (CBT), Novartis Institutes for BioMedical Research, Inc.

9:05 Target Identification Using Chemogenomic and Reactivity-Based Screening

Lyn Jones, Ph.D., Vice President, Chemical Biology, Jnana Therapeutics

Target identification continues to be a resource intensive endeavor that often fails. The value of chemogenomic screening as a technology that can expedite the discovery of therapeutically relevant targets from phenotypic assays will be presented. New developments in protein labeling chemistry with applications to chemoproteomic profiling and molecular pathology studies will also be described.

9:35 A Small Molecule Inhibitor of C5 Complement Protein

Gregory A. Michaud, Ph.D., Chemical Biology and Therapeutics (CBT), Novartis Institutes for BioMedical Research, Inc.

The complement pathway is an important part of the immune system, and uncontrolled activation is implicated in many diseases. The human complement component 5 protein (C5) is a validated drug target within the complement pathway, as an anti-C5 antibody (Soliris) is an approved therapy for paroxysmal nocturnal hemoglobinuria (PNH). Compound 7l (Zhang et al, ACS Med. Chem. Lett., 2012), was recently reported as an inhibitor of the complement pathway, but its molecular target was not identified. Here we report that human C5 is the target for Compound 7I.

10:05 Whole-Genome siRNA Screen Identifying Novel Targets of the TGFβ Pathway

Chris Kitson, Ph.D., Principal Scientist, Fibrosis Biology Discovery, Bristol-Myers Squibb

Transfection of a genome-wide siRNA library into normal human lung fibroblasts enabled identification of novel targets from the TGFβ pathway, using high-content analysis to measure the degree of cellular differentiation. Hits were retested in multiple donors, with additional reagents, and triaged through a series of filters. Targets from the screen are supporting our early fibrosis portfolio.

10:35 Coffee Break in the Exhibit Hall with Poster Viewing and Poster Competition Winner Announced

11:20 Functional Annotation of Biological Processes Targeted by Chemical Libraries

Jeff Piotrowski, Ph.D., Principal Scientist, Target Identification, Yumanity Therapeutics

To characterize the functional diversity of large compound libraries, we developed a highly parallel and unbiased yeast chemical-genetic screening system and screened 7 diverse compound libraries. Our analysis shows that we can visualize the functional diversity of each library, prioritize subsets of compounds that target specific biological processes, globally validate targeted processes, and identify compounds targeting multiple processes. With spontaneous mutant analysis, we can link compounds to targets in yeast, and translate to mammalian orthologs.

11:50 Interrogating the Plasma Membrane Proteome for New Targets

Shaun M. McLoughlin, Ph.D., Senior Research Scientist III, Target Identification and Validation Technologies, AbbVie

Surface proteins play an integral role in the progression of cellular pathology. Consequently, these proteins have been exploited for the development of pharmaceutical therapies. Despite its importance, the surface proteome has remained largely uncharacterized owing to significant analytical challenges, low protein copy number and rapid target degradation. This discussion will detail traditional and modern techniques for plasma membrane protein extraction and their application to models of cancer resistance.

12:20 pm Sponsored Presentation (Opportunity Available)

12:50 Session Break

1:00 Luncheon Presentation to be Announced



1:50 Refreshment Break in the Exhibit Hall with Poster Viewing

Innovative Approaches for Finding Novel Targets

2:35 Chairperson's Remarks

Jeffrey Barrett, Ph.D., Director, Open Targets and Group Leader, The Wellcome Trust Sanger Institute, Genome Research Limited

2:40 Using Human Genetics to Make New Medicines

Jeffrey Barrett, Ph.D., Director, Open Targets and Group Leader, The Wellcome Trust Sanger Institute, Genome Research Limited

Open Targets is a public private initiative to transform drug discovery by enabling systematic identification and prioritisation of targets. We combine large-scale human genetics data and high-throughput gene editing with objective statistical and computational techniques to identify and validate causal links between targets, pathways and diseases. We accelerate and enable research and innovation by making the evidence open and accessible to all (http://targetvalidation.org/).

3:10 Target Identification Strategies for Dermatological Indications

Deepak Kumar Rajpal, Ph.D., Director, Computational Biology, GlaxoSmithKline

We plan to share a framework for developing new therapeutic intervention strategies for psoriasis by computational approaches and utilizing publicly available clinical transcriptomics data sets. We share a proposed a psoriasis disease signature, present approaches to identify potential drug repurposing opportunities and outline a novel target selection methodology. We anticipate that methologies shared here or similar approaches will aid in target discovery in dermatological indication space, support biomarker discovery and the development of new drugs.

3:40 Session Break

3:55 Combinatorial Omics: Leveraging Genomic-Phenomic Modulation for the Interpretation of Large Scale Screens

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

In this talk, we will draw on studies from drug screening and RNAi to describe data mining workflows to go from phenotypic measurements to biological insight. The availability of modern bioinformatics tools and multiple public databases make for very interesting investigations in multimodal data integration. Our goal will be to present a view of what's possible, using case studies from RNAi screening in triple negative breast cancer, and drug screening in glioblastoma.

4:25 Target Identification and Assay Validation for the Tox21 HTS Program

Menghang Xia, Ph.D., Leader, Systems Toxicology, Division of Pre-Clinical Innovation, National Center for Advancing Translational Sciences, NIH

The toxicology in the 21st century (Tox21) program has developed and utilized a quantitative high throughput screening (qHTS) paradigm that has provided a more efficient and cost-effective alternative to traditional tests for profiling the toxicity of environmental chemicals. In this program, approximately 10K environmental chemicals including clinically used drugs have been screened against a panel of biologically relevant cell-based assays. This talk describes the Tox21 program, selection of qHTS-based assays and the various Tox21 screening assays.

4:55 Close of Conference

* 活动内容有可能不事先告知作更动及调整。

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