2016 Archived Content

Phenotypic Screening


Day 1 | Day 2 | Download Brochure

Tuesday, November 1

11:00 am Conference Registration

12:15 pm Luncheon Presentation: Phenotypic Primary Human Cell-Based Assays for Fibrosis

Jeroen DeGroot, Ph.D., Senior Director, Biology, Charles River Laboratories

Human primary cell-based assays representing fibrosis pathophysiology are key for target and drug discovery for fibrotic diseases. Profiling of these assays using compounds targeting various molecular mechanisms validates the translational application. High content imaging in 384 well format allows high throughput screening of small molecule as well as RNAi libraries.

12:45 Dessert Break in the Exhibit Hall with Poster Viewing


Strategies in Phenotypic Screening

1:30 Chairperson’s Opening Remarks

David C. Swinney, Ph.D., CEO, Institute for Rare and Neglected Diseases Drug Discovery (iRND3)

1:35 Strategies that Identified Targets of Medicines Discovered with Phenotypic Screens

David C. Swinney, Ph.D., CEO, Institute for Rare and Neglected Diseases Drug Discovery (iRND3)

Phenotypic screening as a drug discovery strategy identifies candidate medicines independent of specific molecular hypotheses. Subsequently, the candidate medicine can be used to identify the MMOA and target to facilitate development, as well as to identify follow on molecules. A number of different strategies are employed to identify these targets. Successful strategies used to identify targets of first-in-class NMEs discovered with empirical/phenotypic screening will be discussed in this talk.

2:00 The Phenomics Discovery Initiative: Bringing Predictive Biology to the Best Technology

Paul Andrews, Ph.D., Director of Operations, National Phenotypic Screening Centre, University of Dundee; Director and Owner, Stem Cell Solutions

The National Phenotypic Screening Centre was created with >$14M of government investment and launched in 2015 with labs in three top-tier UK Universities: Dundee, Edinburgh and Oxford. We recently announced the Phenomics Discovery Initiative (PDi)—a pre-competitive consortium open to Pharma/Biotech where we use our academic and clinical network to source, develop and screen novel complex disease-relevant phenotypic assays. Janssen/J&J is PDi’s founding member.

2:25 Lessons Learned in Phenotypic Drug Discovery

Fabien Vincent, Ph.D., Associate Research Fellow, Assay Development and Pharmacology, Hit Discovery and Lead Profiling, Pfizer Global Research & Development
This presentation will cover a collection of scientific vignettes (i.e. lessons) based on in-house experience with phenotypic drug discovery and touch on a broad range of topics including designing the best phenotypic assays, primary cells and donor-to-donor variability analysis, hit triage and validation, use and misuse of chemogenomics libraries, and toxicity and safety derisking of PDD hits. 

2:55 Refreshment Break in the Exhibit Hall with Poster Viewing

3:45 Improving the Reproducibility of Cellular Assays and Phenotypic Screens

Anthony M. Davies, Ph.D., Center Director, Translational Cell Imaging Queensland (TCIQ), Institute of Health Biomedical Innovation, Queensland University of Technology

Over the last few years, there have been a number of reports highlighting the problem of poor reproducibility in biological research. Indeed it was reported by Nature News that irreproducible biology research costs approximately $28 billion per year in the U.S. alone. In this presentation, we will describe our plans and current progress in attempting to address this issue specifically in the area of cell-based assays and phenotypic screening. This Australian-led initiative will incorporate and utilize both methodological and technological innovations to meet our project aims. Currently our focus is on the utilization of high-content imaging and analysis for this task.

4:10 Accelerating Drug Discovery through a Dual-Ligand Based Phenotypic Screening Strategy

Neil Carragher, Ph.D., Professor, Drug Discovery, Institute of Genetics and Molecular Medicine, University of Edinburgh

We present our iterative phenotypic screening strategy, which focuses on sub-library screening of small boutique chemical sets across informative/context-based phenotypic assay panels. Using an agile strategy that combines ligand-based inhibitor design and phenotypic screening in an iterative manner, we demonstrate the rapid discovery of an orally-available, ATP-competitive, kinase inhibitor that displays high selectivity and potent antiproliferative and anti-invasive activity against breast cancer cells.

4:35 Close of Day

5:45 ThinkTank Registration

6:00-9:00 Dinner Expert ThinkTank
(SC2): How to Meet the Need for Physiologically Relevant Assays

Separate registration required

Day 1 | Day 2 | Download Brochure

Wednesday, November 2

7:30 am Breakfast Presentation (Sponsorship Opportunity Available) or Morning Coffee


Case Studies in Phenotypic Screening

8:00 Chairperson’s Remarks

Bridget Wagner, Ph.D., Director, Pancreatic Cell Biology and Metabolic Disease, Broad Institute

8:05 A Phenotypic Approach to the Chemical Biology of Diabetes

Bridget Wagner, Ph.D., Director, Pancreatic Cell Biology and Metabolic Disease, Broad Institute

A loss of beta-cell mass and biologically active insulin is a central feature of both type 1 and type 2 diabetes. A chemical means of promoting beta-cell viability or function could have an enormous impact clinically by providing a disease-modifying therapy. Here I will discuss how my group is identifying small molecules that promote beta-cell regeneration, viability and function.

8:30 A Quantitative Systems Pharmacology Program for Identifying Novel Therapeutic Approaches for Huntington’s Disease

Mark Schurdak, Ph.D., Director of Operations, University of Pittsburgh Drug Discovery Institute

We have implemented a Quantitative Systems Pharmacology (QSP) program that determines the mechanism(s) of disease progression and mechanism(s) of action of drugs on multi-scale systems through iterative and integrated computational and experimental methods to inform the development of optimal therapeutic strategies. Using the QSP approach we identified a number of probes with different canonical mechanisms that prevented HD-induced cytotoxicity and have demonstrated that combinations of these probes showed enhanced protective effects relative to single probes suggesting distinct mechanisms may be involved. These data will help guide the elucidation of pathways involved in HD neuroprotection.

8:55 Phenotypic Screening of Human Neuronal Cells Infected with Zika Virus to Identify Lead Compounds for Drug Development

Wei Zheng, Ph.D., Group Leader, Division of Preclinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health

In response to the current global health emergency posed by the Zika virus (ZIKV) outbreak and its link to microcephaly and other neurological conditions, we performed a drug repurposing screen using iPS cell derived human neural progenitor cells and astrocytes. We identified three groups of lead compounds that either protect neuronal cells from Zika virus caused cell death or inhibit virus infection. Our results demonstrate the efficacy of this screening strategy and have identified lead compounds for anti-ZIKV drug development.

9:20 Phenotypic Screening for Cardiomyocyte Proliferation

Jeffrey Saucerman, Ph.D., Associate Professor, Biomedical Engineering, University of Virginia

The adult mammalian heart has a limited ability to regenerate cardiomyocytes. Here, I will discuss our high-content phenotypic screens with primary and human iPSC-derived cardiomyocytes to identify genes and compounds that enhance cardiomyocyte proliferation. We have developed live-cell assays for quantifying changes in cardiomyocyte cell numbers, DNA content, and bi-nucleation. High-content analysis is combined with systems pharmacology analyses to prioritize new therapeutic targets and molecular networks.

9:45 Whole-Organism Chemical Screening Using Zebrafish Larvae Identifies a Role for Sigma-1 Receptors in Controlling Fear Responses

Andrew J. Rennekamp, Ph.D., Research Fellow in Medicine, Massachusetts General Hospital, Harvard Medical School, and Broad Institute

Freezing and fleeing in response to an acute threat is a behavioral trait observed in most animals. The ability to choose an appropriate defense response during a threatening situation has consequences not only for survival but also for mental health. In this talk, I will demonstrate how a new target-agnostic chemical screen was used to discover novel neuroactive small molecules and a role for sigma-1 receptors in defense response selection.

10:10 Networking Coffee Break


Phenotypic Screening of 3D Models

10:40 pm Chairperson’s Remarks

David Nolte, Ph.D., Professor, Physics, Purdue University; CTO, Animated Dynamics, Inc.

10:45 Implementing 3D Phenotypic and Target-Based Models to Interrogate Small Molecule Inhibition of the MAPK Pathway

Lesley Mathews Griner, Ph.D., Investigator II, Lab Head, Molecular Pharmacology, Oncology Research, Novartis Institutes for BioMedical Research

11:10 Phenotypic Screening for Cancer Therapeutic Efficacy in 3D Tissues

David Nolte, Ph.D., Professor, Physics, Purdue University; CTO, Animated Dynamics, Inc.

The three-dimensional cellular context is a key element influencing how cells respond to chemotherapeutics. Cellular adhesions, local membrane forces, intercellular signaling, and interactions with the extracellular matrix provide a microenvironment in which cancer proliferates and within which it responds to treatment. Biodynamic phenotypic profiling images dynamic processes deep inside 3D tissues, testing therapeutic efficacy in vitro while maintaining biological relevance, providing accurate measurements of individual response to therapy.

11:35 Label-Free Optical Molecular Imaging for in situ Viability Screening in 3D Engineered Tissues

Mary-Ann Mycek, Ph.D., Professor and Associate Chair for Translational Research, Department of Biomedical Engineering, College of Engineering & Medical School, University of Michigan

Noninvasive and label-free optical molecular imaging with metrics obtained from quantitative image analysis reliably screened viability in 3D living engineered tissues manufactured from primary human cells. Such optically derived metrics for tissue morphology and function could serve as quality control release criteria for cell-based tissue-engineered devices prior to implantation in patients, a critical regulatory requirement in regenerative medicine.

12:00 Close of Conference



Day 1 | Day 2 | Download Brochure