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.

Choose 2 Short Courses and 2 Conferences/Training Seminars
September 16 Pre-Conference Short Course: SC4: How to Best Utilize 3D Cells, Spheroids and PDX Models in Oncology
September 17-18 Conference: Target Identification and Validation
September 18 Dinner Short Course: SC9: Targeted Protein Degradation Using PROTACs, Molecular Glues and More
September 18-19 Training Seminar: TS4: Practical Phenotypic Screening

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

Lal_MadhuMadhu 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

Doench_JohnJohn 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

Bartholomeusz_GeoffGeoffrey 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

Sheltzer_JasonJason 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

Rockwell_KristinKristin 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

Beijerbergen_RoderickRoderick 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 Transcriptome Profiling and Functional Screening to Identify Genes Driving Biological Responses and Disease Progression

Paul Diehl, PhD, COO, Cellecta, Inc.

Pooled libraries of heterogenous lentiviral constructs have proven to be an effective approach to individually label cells in a target population with cell-specific barcodes and/or other genetic effectors. NGS analysis of targeted multiplex RT-PCR from cell samples enables parallel analysis of differences in gene activation as a result of perturbation. These approaches can be used to gain a more comprehensive understanding of genetic pathways in disease.

12:25 pm Session Break

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

Montana_JohnJohn 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

Gavva_NarenderNarender 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

Bronson_PaolaPaola G. Bronson, PhD, Senior Scientist, 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.

Reaction_Bio_2019 2:55 SPR Binding Studies of Small Molecule Inhibitors of PRMT5

Rebecca Eells, PhD, Associate Director, Biophysical Assays, Reaction Biology Corporation

Epigenetic modifications are dynamic, reversible processes that regulate gene expression without altering DNA sequence. The proteins involved, epigenetic modifiers, are attractive targets for therapeutic discovery/development since abnormal expression/alteration leads to disease. Reaction Biology offers a suite of services for epigenetic drug discovery, including biophysical assays to directly determine the kinetics/affinity of binding to the target. Here we present SPR data for small molecule inhibitors of PRMT5 that engage the target using distinct binding modes.

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

Horn_MoritzMoritz 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 - View All Breakouts

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.

New Trends in Functional Genomics-Based Screening and Technologies

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

  • Screen validation and follow-up with single well CRISPR technology
  • Large-scale screening with cell sensing and response reporters
  • CRISPR screening in primary cells using co-culture systems

Chemical Biology in Drug Discovery

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

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

  • Chemical biology approaches as an avenue for new targets
  • Chemo-proteomics approaches to understand protein degradation
  • Covalent fragment screening for the coupled discovery of targets and leads
  • How can chemical biology approaches complement CRISPR-based technologies?

Use of Advanced Disease Models in Drug Discovery

Moderators: 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

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

  • Developing multi-cellular 3D cell culture models for high-throughput screening
  • Specific 3D models for target identification and validation screens
  • Challenges with high-throughput screens utilizing 3D spheroid models
  • Patient-derived xenograft ex vivo (PDXEx) models as a screening platform
  • Evaluation of microphysiological systems and models for efficacy, as well as safety studies

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

Martin_JeffJeff 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.

Manjinder Sandhu, CEO, Reader in Global Health & Population Sciences, University of Cambridge, Omnigen Biodata

Large-scale clinical and biodata resources have the potential to spur innovation in drug discovery and target validation and real world data analyses—enabling precision health initiatives and  informing health policy to improve the health of individuals and populations. We now have opportunities to create and integrate real-world health and genomic data globally. I outline the value of such resources and approaches to build biodata alongside participants and providers—enabling compliance with data protection and privacy. 

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

Xu_HuaHua 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

Bouvier_MichelThis 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

Lichtarge_OliverOlivier Lichtarge, MD, PhD, Molecular and Human Genetics, Computational and Integrative Biomedical Research Center, Baylor College of Medicine

-Virtual Screening: A Post-Structural Era

Irwin_JohnJohn 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

Anjan Chakrabarti, Vice President, Discovery Chemistry, Syngene International Ltd

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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