Target Identification and Validation


( 标的发现与验证 )

Finding novel, druggable targets for therapeutic intervention remains a top priority for the pharma/biotech industry. It also remains a formidable challenge and companies continue to invest a lot of time and resources in identifying and validating targets that will yield viable drugs. What are the challenges in target discovery today? What new tools and strategies are being used to identify targets and how well are they working? What’s being done to adequately validate the targets once they are identified? What efforts are being taken to go after difficult or “undruggable” targets? Cambridge Healthtech Institute’s conference on Target Identification and Validation will bring together leading experts to discuss some of these critical issues. This is a unique opportunity to meet and network with biologists and screening groups from around the world to share ideas and set up collaborations.

Final Agenda


1:00 pm Pre-Conference Short Course Registration
Click here for details on short courses offered.


7:00 am Registration Open and Morning Coffee

Target Discovery Using Advanced Disease Models

8:00 Organizer's Welcome Remarks

8:05 Chairperson’s Opening Remarks

Roderick Beijersbergen, PhD, Group Leader, Division of Molecular Carcinogenesis and NKI Robotics and Screening Center, The Netherlands Cancer Institute

8:10 Exploring Opportunities – Synergy in Translational Science

Madhu Lal-Nag, PhD, Program Lead, Research Governance Council, Office of Translational Sciences, Center for Drug Evaluation & Research, U.S. Food and Drug Administration

Translation is the process of turning observations in the laboratory, clinic and community into interventions that improve the health of individuals and the public — from diagnostics and therapeutics to medical procedures and behavioral changes. We will explore the challenges and solutions of identifying novel targets for rare diseases.

8:40 FEATURED PRESENTATION: CRISPR Screens in Challenging Model Systems

John Doench, PhD, Associate Director, Genetic Perturbation Platform, Broad Institute of Harvard and MIT

CRISPR screens have become the method of choice for large-scale assessment of gene function, but implementation in complex model systems remains a significant challenge. Here I will present the optimization of mouse models to discover modulators of tumor immunotherapy. Combinatorial screens present similar challenges and will also be discussed.

9:10 Aspartate/Aspergine Beta Hydroxylase (ASPH): A Potential Therapeutic Target for Overcoming HER2 Resistant Metastatic Breast Cancer

Geoffrey Bartholomeusz, PhD, Associate Professor and Director, Target Identification and Validation Program, Department of Experimental Therapeutics, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center

Inflammatory breast cancer (IBC), is a rare and extremely aggressive subtype of breast cancer. Mis-diagnosis and lack of effective therapies further compound the poor clinical outcome of this disease. We observed that Aspartate-beta-hydroxylase (ASPH), known to contribute to the aggressive behavior of cancers, is highly expressed in IBC. Our studies have also suggested that targeting ASPH could potentially improve our ability to treat IBC.

9:40 Grand Opening Coffee Break in the Exhibit Hall with Poster Viewing

CRISPR Screening for Target & Off-Target Identification

10:25 Off-Target Toxicity is a Common Mechanism-of-Action of Cancer Drugs Undergoing Clinical Trials

Jason Sheltzer, PhD, Principal Investigator, Cold Spring Harbor Laboratory

We have found that cancer cells can tolerate CRISPR-Cas9 mutagenesis of many reported cancer drug targets with no loss in cell fitness. In contrast, RNAi hairpins and small-molecules designed against those targets continue to kill cells, even when their putative target has been knocked out. We suggest that many RNAi constructs and clinical compounds exhibit much greater off-target killing than previously realized, and several dozen clinical trials have been initiated based on irreproducible preclinical research.

10:55 Functional Genomics Screening in Primary Human T Cells to Identify Novel Targets for Autoimmune Diseases

Kristin Rockwell, Senior Scientist, Discovery Sciences, Pfizer

To identify new targets/pathways involved in autoimmune disorders, we have successfully developed two high throughput functional genomics screening platforms based on primary human T-cells, high throughput flow cytometry (HT-FCM) and nucleofection technology. A siRNA screen encompassing 2,000 genes was completed, followed by a CRISPR screen to validate hits. Assay design and optimization as well as the results of these functional genomics screening efforts in primary human T cells will be presented.

11:25 Beyond Viability: Sensor-Based CRISPR Screening

Roderick Beijersbergen, PhD, Group Leader, Division of Molecular Carcinogenesis and NKI Robotics and Screening Center, The Netherlands Cancer Institute

Large scale CRISPR screens have proven their power in many different screening models, predominantly based on read-outs associated with proliferation or survival. Recently, more complex screening models such as co-cultures, cell surface marker expression or reporter gene activation have been applied. The next step is the use of even more sophisticated reporter systems that measure specific biological processes or pathways. The development and application of examples of such systems will be discussed.

11:55 Presentation to be Announced

12:25 pm Session Break

12:35 Luncheon Presentation: A Blueprint for Translational Integrated Drug Discovery

John Montana, PhD, Corporate Vice President, Integrated Drug Development and Strategic Projects, Charles River

What does the future of your drug discovery program look like? Historically high R&D costs and low success rates have emphasized the need to identify drugs focused on translationally relevant targets in the most cost and time efficient way. There are innovative ways to progress truly translational drug discovery projects in an increasingly complex and competitive environment. These case studies will demonstrate how to optimize operations and build a new model for drug development that emphasizes collaboration and novel approaches.

1:15 Refreshment Break in the Exhibit Hall with Poster Viewing

Genetics-Based Target Discovery

1:50 Chairperson’s Remarks

Paola G. Bronson, PhD, Scientist II, Human Target Validation Core (Translational Biology), Biogen, Inc.

1:55 Human Genetics-Based Target Identification & Validation for 2x Success in the Clinic

Narender R. Gavva, PhD, Director, Early Target Discovery, Takeda California, Inc.

Most expensive clinical pipeline attrition occurs for lack of efficacy. This could be due to an over-estimation of “effect size” in target validation efforts in preclinical species/models, mismatch of candidate mechanism and clinical indication(s), clinical trial design, etc. Utilization of patient genetics as target validation is yielding targets and mechanisms with higher success in the clinic (estimated at ~2X). This presentation covers different types of human genetics and how to follow up for target validation.

2:25 Genetic Studies of MS for Drug Discovery

Paola G. Bronson, PhD, Scientist II, Human Target Validation Core (Translational Biology), Biogen, Inc.

Over 200 loci are associated with multiple sclerosis (MS) susceptibility, but the non-immune component is unknown and the genetic contribution to disease severity is undefined. The goals of this study were: (a) to partition out the non-immune component of MS susceptibility loci; and (b) to evaluate the impact of common genetic variants on disease severity measures (brain atrophy and serum neurofilament light) using MS clinical trial participants. We applied a colocalization strategy to identify neurological targets for MS and potential adverse events, alternate indications, and biomarkers. Our study represents a step toward using objective, quantitative traits to examine the genetics of MS progression.

2:55 Sponsored Presentation (Opportunity Available)

3:25 Refreshment Break in the Exhibit Hall with Poster Viewing and Poster Competition Winner Announced

4:05 Unbiased Compound-Target Interface Mapping through Forward Genetics

Moritz Horn, CEO, Acus Laboratories GmbH, Max Planck Institute for Biology of Ageing

Identifying druggable target structures and understanding an active molecules target space remain challenges in drug development. We established a chemical mutagenesis approach that allows entirely unbiased identification of small molecule targets at amino acid resolution, literally mapping compound-target interaction surfaces. Applied to relevant cellular systems, our screen uncovers specific drug target structures as well as entirely new ‘druggable’ targets in an unbiased and genome-wide manner.

4:35 An Evolutionary Cross-Species Approach to Context-Specifically Identify Essential Genes Using CRISPR Screens

Raghuvir “Ram” Viswanatha, PhD, Postdoctoral Research Fellow, Blavatnik Institute of Genetics, Harvard Medical School

Insect cell-lines are simple model animal cell-lines, possessing few paralogs while retaining most of the core signaling pathways underlying human disease. My research introduces new CRISPR-based functional screening strategies to insect cell-lines allowing high-resolution, genome-wide dissection of growth and signaling and uncovering new players. I will discuss published and ongoing work related to gene paralogy and redundancy, nuclear steroid hormone transport and signaling, and mTor-dependent control of cell proliferation.

5:05 Interactive Breakout Discussion Groups

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. Visit the conference website for discussion topics and moderators.

6:05 Welcome Reception in the Exhibit Hall with Poster Viewing (Sponsorship Opportunity Available)

7:10 Close of Day


7:30 am Registration Open and Morning Coffee

Case Studies Using Phenotypic Screening & Chemical Biology Approaches

8:00 Chairperson’s Remarks

Jaimeen Majmudar, PhD, Principal Scientist, Chemical Biology, Pfizer, Inc.

8:05 Comparison of Target Identification Approaches Using an IRAK4 Inhibitor

Jeff Martin, PhD, Scientist II, Chemical Biology & Proteomics, Biogen, Inc.

Phenotypic screening is a key starting point for drug discovery that allows for the identification of small molecules that produce a beneficial phenotype in disease relevant models. Target identification of these small molecule hits from phenotypic screens is challenging due to the inherent complexity of the cellular systems involved. Comparison of multiple target identification approaches will be described in this talk including clickable photoprobes, affinity enrichment, and CETSA.

8:35 Influence of Post-Translational Modifications, Metals and Partner Proteins on the Fe-S Cluster Synthesis Machinery

Jaimeen Majmudar, PhD, Principal Scientist, Chemical Biology, Pfizer, Inc.

Recombinant proteins are routinely utilized for high-throughput screening for identification of lead chemical equity for drug development. While this has proven of immense value, translation of biochemical screens into cellular assays can be challenging. Using the example of the Fe-S cluster machinery proteins NFS1-ISD11-ACP-ISCU2 and FXN, we show that it is critical to understand recombinant systems in the context of metal dependence, complex formation and post-translational modifications.

9:05 Presentation to be Announced

9:35 Coffee Break in the Exhibit Hall with Poster Viewing

10:20 Application of Chemical Proteomics in Drug Discovery: Selectivity Profiling and Target Identification

Hua Xu, PhD, Associate Research Fellow, Medicine Design, Pfizer

Chemical proteomics is a powerful and impactful tool and has been frequently used to address a number of key questions in drug discovery. A few case studies on selectivity profiling and target identification will be described to demonstrate its impact on preclinical and clinical programs at Pfizer.

10:50 - 11:50 BRIDGING LUNCHEON PANEL DISCUSSION: GPCRs: Leveraging Years of Data for Transformative Drug Discovery

This 1-hour panel moderated by Michel Bouvier, PhD, Principal Investigator & CEO, Institute for Research in Immunology and Cancer (IRIC) and Professor, Department of Biochemistry and Molecular Medicine, Faculty of Medicine, Université de Montréal will feature two talks related to new horizons in GPCR drug discovery. The talks will be followed by a question and answer session.

-GPCR Mutations: Towards a More Personalized Drug Discovery

Olivier Lichtarge, MD, PhD, Molecular and Human Genetics, Computational and Integrative Biomedical Research Center

-Virtual Screening: A Post-Structural Era

John Irwin, PhD, Adjunct Professor, Department of Pharmaceutical Chemistry, University of California, San Francisco

11:20 Conference Registration for Programs 1B-7B

11:50 Session Break

Click here for full abstracts.

12:20 pm Event Chairperson’s Opening Remarks

An-Dinh Nguyen, Team Lead, Discovery on Target 2019, Cambridge Healthtech Institute


12:30 Plenary Keynote Introduction

12:40 Base Editing: Chemistry on a Target Nucleotide in the Genome of Living Cells

David R. Liu, PhD, Howard Hughes Medical Institute Investigator, Professor of Chemistry & Chemical Biology, Harvard University



1:20 PROTACs: Past, Present, and Future

Craig M. Crews, PhD, Professor, Chemistry; Pharmacology; Molecular, Cellular & Developmental Biology; Yale University



2:00 Close of Plenary Keynote Program

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

2:45 Close of Target Identification and Validation Conference

* 活动内容有可能不事先告知作更动及调整。

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