high-content analysis & phenotypic screening · 2 | highcontentanalysis.com chi’s thirteenth...

HIGH-CONTENT ANALYSIS & PHENOTYPIC SCREENING

Cambridge Healthtech Institute’s Thirteenth Annual

FEBRUARY 11 - 12, 2016 | HILTON SAN DIEGO RESORT & SPA | SAN DIEGO, CA

HighContentAnalysis.com

FEATURED SPEAKERS Paul Andrews Director, National Phenotypic Screening Centre University of Dundee

Anthony M. Davies Director, Translational Cell Imaging Queensland University of Technology

Erik Hett Team Leader, Chemical & Molecular Therapeutics Biogen

Susanne Heynen-Genel Director, High-Content Screening Sanford Burnham Prebys Medical Discovery Institute

Zhuyin Li Team Lead, Lead Discovery & Optimization Bristol-Myers Squibb

Ulrich Schopfer Head, Integrated Lead Discovery Novartis

D. Lansing Taylor Director, University of Pittsburgh Drug Discovery Institute

Alan Waggoner Director, Molecular Biosensor and Imaging Center Carnegie Mellon University

Wei Zheng Group Leader, Preclinical Innovation NCATS

COVERAGE INCLUDES:• Case studies in phenotypic drug discovery

• High-content and phenotypic screening of 3D cell culture

• Novel models for screening, including organoids, organotypic primary cells, iPSCs and spheroids

• Assay development and case studies in HCA

• Target/pathway identification and validation

• Data analysis for phenotypic and high-content screening

• Chemical genomics and chemical proteomics

• Quantitative systems pharmacology

• Live-cell imaging

• Ultra-high resolution imaging

DINNER COURSES:

Introduction to High-Content Phenotypic Screening

Expert ThinkTank: How to Meet the Need for Physiologically Relevant Assays

THE ORIGINAL HIGH-CONTENT ANALYSIS EVENT

SAVE UP TO $350REGISTER BY NOVEMBER 13

2 | HighContentAnalysis.com

CHI’s Thirteenth Annual High-Content Analysis meeting, the premier event showcasing the latest advancements in HCA applications and technologies, returns to San Diego with a new program. Over the years we have observed the technology mature and its adoption spread into many areas of compound screening/evaluation and functional analysis. The High-Content Analysis meeting will focus on the next steps of technology development, including screening of 3D and physiologically relevant complex models, ultra-high resolution and high-throughput imaging, more advanced image analysis and data management, and new assays and applications.

The co-located Second Annual Phenotypic Screening meeting will address the advantages of phenotypic screening vs. target-based screening, and focus on assay development, selection of physiologically relevant models and subsequent target identification, as well as case studies of phenotypic screens from leading pharma. Join the original High-Content Analysis event and get access to two tracks featuring a cutting-edge scientific agenda, expanded exhibit hall and technology showcases, and interactive dinner courses.

ABOUT THE EVENT

DISTINGUISHED SPEAKERS• Paul Andrews, Ph.D., Director, National Phenotypic Screening Centre,

University of Dundee, UK

• Ulrich Broeckel, M.D., Professor, Pediatrics, Medical College of Wisconsin

• Steven Chi-Ming Chen, Specialist, Pharmaceutical Chemistry, Small Molecule Discovery Center at UCSF, Mission Bay

• Sylvain Costes, Ph.D., Principal Investigator, Cancer and DNA Damage Response, Lawrence Berkeley National Laboratory

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

• Mohanraj Dhanabal, Ph.D., Group Leader, Lead Discovery Technology, EMD Serono

• Regis Doyonnas, Ph.D., Senior Principal Scientist, High-Content Screening and HTS-Flow Cytometry, Primary Pharmacology Group, Pfizer

• Lauren Drowley, Ph.D., Associate Principal Scientist, AstraZeneca

• Su Guo, Ph.D., Professor, Bioengineering and Therapeutic Sciences, University of California, San Francisco

• Erik Hett, Ph.D., Team Leader, Senior Scientist, Chemical & Molecular Therapeutics, Biogen

• Susanne Heynen-Genel, Ph.D., Director, High-Content Screening Systems, Sanford Burnham Prebys Medical Discovery Institute

• Charles C. Hong, M.D., Ph.D., Associate Professor, Cardiovascular Medicine, Pharmacology, and Cell & Developmental Biology, Vanderbilt University School of Medicine

• Shane Horman, Ph.D., Research Investigator, Advanced Assays, Genomics Institute of the Novartis Research Foundation

• Tae-Wan Kim, Ph.D., Associate Professor, Department of Pathology & Cell Biology, Columbia University Medical Center

• Fred King, Ph.D., Research Investigator, Novartis Institute for BioMedical Research

• Beatrice Knudsen, M.D., Ph.D., Director, Translational Pathology, Cedars Sinai Medical Center

• Daniel V. LaBarbera, Ph.D., Associate Professor, Drug Discovery and Medicinal Chemistry, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado

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

• Ming Lei, Senior Scientist, Lead Discovery & Optimization, Bristol-Myers Squibb

• Vance Lemmon, Ph.D., Professor and Chair, Developmental Neuroscience, The Miami Project to Cure Paralysis, University of Miami

• Zhuyin Li, Ph.D., Translational Biomarker Team Lead, Lead Discovery & Optimization, Bristol-Myers Squibb

• David J. Logan, Ph.D., Computational Biologist, Imaging Platform, Broad Institute of Harvard and MIT

• Lisa Minor, Ph.D., President, In V itro Strategies, LLC

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

• Matthias Nees, Ph.D., Coordinator, HCSLab, Turku Science Park/Finland

• Imran Rizvi, Ph.D., Instructor, Medicine and Dermatology, Brigham and Women’s Hospital, Massachusetts General Hospital, Harvard Medical School

• Nathan Ross, Ph.D., Senior Investigator, High Throughput Biology Group Leader, Novartis Institutes for BioMedical Research

• Krishanu Saha, Ph.D., Assistant Professor, Biomedical Engineering, University of Wisconsin, Madison

• Jeff Saucerman, Ph.D., F.A.H.A., Associate Professor, Biomedical Engineering, University of Virginia

• Enrico Schmidt, Ph.D., Lab Head and Investigator, Center for Proteomic Chemistry, Integrated Lead Discovery, Novartis Pharma AG

• Ulrich Schopfer, Ph.D., Executive Director and Head, Integrated Lead Discovery, Novartis Institutes for BioMedical Research

• Mark Schurdak, Ph.D., Research Associate Professor, Computational and Systems Biology, University of Pittsburgh; Director, Drug Discovery Institute

• D. Lansing Taylor, Ph.D., Director, University of Pittsburgh Drug Discovery Institute and Allegheny Foundation Professor, Computational and Systems Biology, University of Pittsburgh

• Andreas Vogt, Ph.D., Associate Professor, Computational and Systems Biology, University of Pittsburgh

• Alan Waggoner, Ph.D., Professor, Biological Sciences, and Director, Molecular Biosensor and Imaging Center, Carnegie Mellon University

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

HighContentAnalysis.com | 3

SPONSORSHIP, EXHIBIT, AND LEAD GENERATION OPPORTUNITIESCHI offers comprehensive sponsorship packages which include presentation opportunities, exhibit space, branding and networking with specific prospects. Sponsorship allows you to achieve your objectives before, during, and long after the event. Any sponsorship can be customized to meet your company’s needs and budget. Signing on early will allow you to maximize exposure to qualified decision-makers.

Podium Presentations – Available Within the Main Agenda!Showcase your solutions to a guaranteed, targeted audience. Package includes a 15- or 30-minute podium presentation within the scientific agenda, exhibit space, on-site branding, access to cooperative marketing efforts by CHI, and more.

Breakfast & Luncheon Podium PresentationsOpportunity includes a 30-minute podium presentation. Boxed lunches are delivered into the main session room, which guarantees audience attendance and participation. A limited number of presentations are available for sponsorship and they will sell out quickly. Sign on early to secure your talk!

Invitation-Only VIP Dinner/Hospitality SuiteSponsors will select their top prospects from the conference pre-registration list for an evening of networking at the hotel or at a choice local venue. CHI will extend invitations and deliver prospects, helping you to make the most out of this invaluable opportunity. Evening will be customized according to sponsor’s objectives i.e.:• Purely social• Focus group

• Reception style• Plated dinner with specific

conversation focus

Exhibit - Sign on by November 13th and Save $300!Exhibitors will enjoy facilitated networking opportunities with qualified delegates. Speak face-to-face with prospective clients and showcase your latest product, service, or solution.

Additional branding and promotional opportunities are available, including:• Conference Tote Bags• Literature Distribution (Tote Bag Insert

or Chair Drop)

• Badge Lanyards• Padfolios• Program Guide Advertisement

Looking for additional ways to drive leads to your sales team? CHI’s Lead Generation Programs will help you obtain more targeted, quality leads throughout the year. We will mine our database of 800,000+ life science professionals to your specific needs. We guarantee a minimum of 100 leads per program! Opportunities include:• Whitepapers • Web Symposia

• Custom Market Research Surveys• Podcasts

For sponsorship and exhibit information, please contact:Katelin FitzgeraldSenior Manager, Business Development781-972-5458 | [email protected]

Showcase Your Research & Advancements - Present a Poster & Save!Cambridge Healthtech Institute encourages attendees to gain further exposure by showcasing current research in a dedicated poster session.- Present your work to the leading pharmaceutical and academic

researchers and scientists- Gain exposure through the inclusion of your research abstract

in conference materials- Receive $50 off your registration fee Learn more at HighContentAnalysis.com

HOTEL & TRAVEL INFORMATION Conference Venue and Hotel: Hilton San Diego Resort & Spa1775 East Mission Bay DriveSan Diego, CA 92109Phone: 619-276-4010

Reservations: Go to the travel page of www.HighContentAnalysis.com

Discounted Room Rate: $185 s/dDiscounted Room Rate Cutoff Date: January 12, 2016

Go to the travel page www.HighContentAnalysis.com for additional info

WEB PARTNERS

LEAD SPONSORING PUBLICATIONS

SPONSORING PUBLICATIONS

Diagnostics World

PARTNERING ORGANIZATION


HIGH-CONTENT ANALYSIS PHENOTYPIC SCREENINGHIGH-CONTENT ANALYSIS FOR

IMMUNOTHERAPY DEVELOPMENT

10:30 A Paradigm Shift in Immune Cell-Mediated Immuno-Modulatory Responses Using High-Throughput FACS AnalysisMohanraj Dhanabal, Ph.D., Group Leader, Lead Discovery Technology, EMD Serono

11:00 High-Content Imaging Assays to Elucidate Antibody Mediated Antigen EndocytosisMing Lei, Senior Scientist, Lead Discovery & Optimization, Bristol-Myers SquibbUnderstanding the mechanisms of antibody mediated antigen endocytosis is essential for new biologics drug discovery. We developed a multifaceted internalization assay platform to deliver a comprehensive kinetic data package that offers quantitative information on the various aspects of cellular activities of drug-target interactions. We applied high-content internalization assays to a number of immuno-oncology drug discovery programs and identified novel mechanism of action.

11:30 Phenotypic Drug Discovery: The Use of 3-D Culture and Image-Based Multi-Parametric ProfilingSteven Rust, Senior Manager, R&D, MedImmune

12:00 pm Luncheon Presentation (Sponsorship Opportunity Available) or Lunch on Your Own

3D CELLULAR MODELS (Cont.)

10:30 Label-Free Nonlinear Optical Microscopy for Non-Invasive Viability Screening in 3D Engineered TissuesMary-Ann Mycek, Ph.D., Professor and Associate Chair for Translational Research, Biomedical Engineering, College of Engineering & Medical School, University of MichiganLabel-free nonlinear optical microscopy with quantitative image analysis reliably and non-invasively screened viability in 3D living engineered tissues manufactured from primary human cells. Optically-derived metrics for tissue morphology and function could serve as release criteria for cell-based tissue-engineered devices prior to implantation in patients, a critical regulatory requirement in regenerative medicine. Prospects for rapid, automated tissue assessment will be discussed.

11:00 Bioengineering Approaches and High-Content Analysis Routines to Characterize Heterogeneity and Treatment Response in 3D Tumor ModelsImran Rizvi, Ph.D., Instructor, Medicine and Dermatology, Brigham and Women’s Hospital, Massachusetts General Hospital, Harvard Medical SchoolAmong the challenges associated with scaling complex cell-based screening platforms is balancing biological relevance with requirements for high-content analysis. Development of a quantitative analysis framework for a microfluidic 3D tumor model and one that restores heterotypic cell signaling will be presented.

11:30 Development of Physiologically Relevant Screening Platforms to Probe Various Disease PathologiesMadhu Lal-Nag, Ph.D., Acting Team Lead, RNAi Screening Facility, National Center for Advancing Translational Sciences, National Institutes of HealthHistorically, screening for oncology directed compounds has been performed in 2-dimensional monolayer cultures which fail to replicate the complex architecture and the microenvironment of tumors in vivo. In vitro model platforms that are designed to be biologically relevant fill a critical gap between the cellular and animal model domains and offer the opportunity to study, screen and select compounds that are therapeutically attractive in real-time.

12:00 pm Luncheon Presentation (Sponsorship Opportunity Available) or Lunch on Your Own

WEDNESDAY, FEBRUARY 10

5:00-6:00 pm Short Course Registration and Main Conference Pre-Registration

THURSDAY, FEBRUARY 11

7:30 am Conference Registration and Morning Coffee

PHENOTYPIC AND HIGH-CONTENT SCREENING IN 3D CELLULAR MODELS8:00 Chairperson’s Opening RemarksAnthony M. Davies, Ph.D., Center Director, Translational Cell Imaging Queensland (TCIQ), Institute of Health Biomedical Innovation, Queensland University of Technology

8:15 The Trials and Tribulations of Complex Phenotypic ScreeningShane Horman, Ph.D., Research Investigator, Advanced Assays, Genomics Institute of the Novartis Research FoundationWith the emergence of new biomimetic phenotypic screening platforms comes the inevitable complexities and technical challenges associated with such initiatives. Side-stepping assay-related landmines on the road to drug discovery is an iterative process, characterized by repeated trial and error. Herein I present benefits and potential pitfalls of complex and multi-culture 3D cell models currently used for drug discovery in the pharmaceutical industry.

8:45 The Challenges of Identifying Cellular Phenotypes in 3D in vitro Cellular Assay SystemsAnthony M. Davies, Ph.D., Center Director, Translational Cell Imaging Queensland (TCIQ), Institute of Health Biomedical Innovation, Queensland University of TechnologyCurrently, one the biggest drivers in the field of translational research is the need to improve the relevance of cell-based assays. To achieve this goal many investigators are turning their attention to high-content analysis used in conjunction with primary cells and/or 3D cell assay models. Despite the potential benefits that these new experimental approaches may offer, their use has not been without both technical and practical difficulties. In this presentation we will discuss the challenges we have encountered here at TCIQ and the solutions that we have arrived at to meet our research objectives.

9:15 Sponsored Presentation (Opportunity Available)

9:45 Coffee Break in the Exhibit Hall with Poster Viewing

6:00-9:00 pm (SC1) DINNER SHORT COURSE: High-Content Phenotypic ScreeningThe ever-increasing demand for improved productivity in research through the generation of robust analysis outputs has driven both the development and deployment of automated high-content analysis (HCA) and phenotypic cell-based approaches to drug discovery. In contrast to the more traditional cellular analysis and target-based approaches, here the researcher is able to evaluate the efficacy of potential therapeutics by monitoring the physiological state of cells through the simultaneous analysis of multiple cellular parameters in the context of an intact biological system. This course will cover the key features of HCS/A technologies and the best approaches to using these technologies for phenotypic cell-based screening.Instructor: Anthony M. Davies, Ph.D., Center Director, Translational Cell Imaging Queensland (TCIQ), Institute of Health Biomedical Innovation, Queensland University of Technology Separate registration required. Please visit www.HighContentAnalysis.com for further information.


HIGH-CONTENT ANALYSIS PHENOTYPIC SCREENINGMACHINE LEARNING AND SYSTEMS BIOLOGY

APPLIED TO HIGH-CONTENT SCREENING

1:25 Chairperson’s RemarksVance Lemmon, Ph.D., University of Miami

1:30 Rapid Deconvolution of Pharmacological Targets for Drug DiscoveryVance Lemmon, Ph.D., Professor and Chair, Developmental Neuroscience, The Miami Project to Cure Paralysis, University of MiamiTarget-based screening is an efficient technique for identifying potent modulators of individual targets. In contrast, phenotypic screening can identify drugs with multiple targets; however, these targets remain unknown. To address this gap, we have combined machine learning and information theory. This allowed us to identify targets as well as others whose targeting should be avoided to achieve a desired biological outcome.

2:00 Quantifying Complex Phenotypes Using Open Source Machine Learning ToolsDavid J. Logan, Ph.D., Computational Biologist, Imaging Platform, Broad Institute of Harvard and MITBiologists increasingly use more complex, physiologically relevant systems for high-throughput drug screening. We have successfully devised image analysis workflows for complex systems using machine learning in multiple stages of the image analysis pipeline. We expect this combination of free, open-source tools to be broadly useful across difficult image analysis domains.

2:30 Discovery of Cardiac Signaling Networks by High-Content ImagingJeff Saucerman, Ph.D., F.A.H.A., Associate Professor, Biomedical Engineering, University of VirginiaBiochemical and mechanical cues can cause the heart to remodel in a variety of ways, involving changes in cardiac myocyte size and shape, proliferation, apoptosis and fibrosis. While it is well recognized that these responses are coordinated by signaling and gene regulatory networks, their complexity has prevented an integrated understanding of how these responses are coordinated at the network level. In this talk, I will provide several examples of how we have combined high-content imaging and systems biology modeling to identify signaling networks that control cardiac myocyte phenotypes. These include morphological analysis to identify pathways that regulate myocyte elongation, texture analysis for automated measures of sarcomere organization, and cell cycle analysis to quantify cardiac myocyte proliferation.


3:15 Refreshment Break in the Exhibit Hall with Poster Viewing

IMPLEMENTING PHENOTYPIC SCREENING1:25 Chairperson’s RemarksD. Lansing Taylor, Ph.D., University of Pittsburgh

1:30 The Role of Phenotypic Screening in Quantitative Systems Pharmacology (QSP)D. Lansing Taylor, Ph.D., Director, University of Pittsburgh Drug Discovery Institute and Allegheny Foundation Professor, Computational and Systems Biology, University of PittsburghWe have implemented a quantitative systems pharmacology platform for drug discovery and the advancement of personalized medicine. Our first three programs are in metastatic breast cancer, hepatocarcinoma and Huntington’s disease. Phenotypic screening plays a central role in this iterative and integrated approach.

2:00 Linking Industry with Academia at the UK’s National Phenotypic Screening Centre: Bringing Technology to the BiologyPaul Andrews, Ph.D., Director, National Phenotypic Screening Centre, University of Dundee, UKUnderstanding the molecular mechanisms underlying disease still remains a major challenge for academia and industry. Only through an in-depth understanding of diseases starting at the patient level and working down through to organ, tissue and cell behavior, can the myriad intracellular biochemical networks, pathways and targets that orchestrate cell function be put into their true context. Drug development costs are unsustainably high with the low clinical efficacy and late stage failures partly due to the prevailing emphasis on molecular targets (assayed outside of their physiological or pathophysiological context). Phenotypic drug discovery (PDD) encompasses a range of approaches that allow the quantitative measurement of the observable manifestations of the complex systems operating at the subcellular and cellular level.

2:30 Phenotypic Screening from Target ID to Profiling Cellular Function in Early Stage Drug DiscoverySusanne Heynen-Genel, Ph.D., Director, High Content Screening Systems, Sanford Burnham Prebys Medical Discovery InstitutePhenotypic screening has been experiencing a resurgence in the last few years. SBP Medical Discovery Institute started to incorporate high-throughput imaging assays to quantify cellular phenotypes into early stage drug discovery 10 years ago. Examples of image-based phenotypic screens will outline how phenotypic imaging assays have been employed to enable drug discovery from target identification to high-throughput screening of large libraries and profiling of cellular function of small molecules.


3:15 Refreshment Break in the Exhibit Hall with Poster Viewing

ORGANOIDS AND 3D ORGANOTYPIC CELL CULTURE4:00 Phenotypic Screening to Accelerate Lead Discovery and Drug RepositioningZhuyin Li, Ph.D., Translational Biomarker Team Lead, Lead Discovery & Optimization, Bristol-Myers SquibbPotential leads from high-throughput screening (HTS)-based drug discovery approaches often result in a high lead attrition rate, due in part to lack of disease relevant in vitro cellular models and predictive assay technologies. Recent developments in phenotypic screening using disease-relevant cellular models and advanced assay technologies have reduced attrition rate and improved in vitro to in vivo connectivity. In this presentation, three examples will be highlighted: 1) identification of potent inhibitors of tumor growth and metastasis for an anaplastic thyroid cancer in vivo model using in vitro phenotypic screening; 2) phenotypic screening for potential drug repositioning to promote functional remyelination in vivo; 3) phenotypic screening using 3D organotypic cellular models that mimic omental tissue for the identification of ovarian cancer metastasis inhibitors with demonstrated efficacy in vivo.

4:30 A 3D Phenotypic Screening Platform to Mimic Tumor Microenvironment and Tissue ArchitectureMatthias Nees, Ph.D., Coordinator, HCSLab, Turku Science Park/Finland

5:00 High-Throughput Imaging: Focusing in on Cancer Drug Discovery in 3DDaniel V. LaBarbera, Ph.D., Associate Professor, Drug Discovery and Medicinal Chemistry, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of ColoradoHigh-throughput imaging drug discovery using 3D tissue culture and organoids has been limited due to practical and technical hurdles. This presentation will describe recent advances that we have developed for volumetric high-content analysis using multicellular tumor spheroids suitable for high-content screening drug discovery.

5:30-6:30 Welcome Reception in the Exhibit Hall with Poster Viewing5:30 Short Course Registration

6:30-9:00 (SC2) DINNER EXPERT THINKTANK: How to Meet the Need for Physiologically Relevant AssaysIt used to be adequate to build target-specific and robust assays to drive lead optimization. These assays were relatively inexpensive and reliable and could be counted on to provide chemists with usable results. However, with time, it has become apparent that it is not enough to be robust and target specific. To build therapies for patients, we need to have assays that are more predictive of patient outcome. The current buzz words are “physiologically relevant assays.” This session will explore the need for physiologically relevant assays and explore the ways that we can achieve this endpoint.Moderator: Lisa Minor, Ph.D., President, In Vitro Strategies, LLCSeparate registration required. Please visit www.HighContentAnalysis.com for further information.


HIGH-CONTENT ANALYSIS PHENOTYPIC SCREENINGINNOVATION IN HCA ASSAY DEVELOPMENT

10:55 Chairperson’s RemarksAlan Waggoner, Ph.D., Carnegie Mellon University

11:00 Fluorescent Biosensors for Live Cell Protein TraffickingAlan Waggoner, Ph.D., Professor, Biological Sciences, and Director, Molecular Biosensor and Imaging Center, Carnegie Mellon UniversityLive cell health and function is controlled by interactions between thousands of types of proteins that are parts of regulatory pathways. We are developing a toolkit of fluorescent probes (biosensors) for quantifying these regulation pathways. Emphasis will be placed on high-throughput quantification of membrane surface channels, transporters and signaling receptors. I will, as well, cover new, targeted physiological indicators for membrane potential, calcium, sodium, potassium and pH.

11:30 High-Content Analysis of CRISPR-Cas9 Gene-Edited Human Embryonic Stem CellsKrishanu Saha, Ph.D., Assistant Professor, Biomedical Engineering, University of Wisconsin, MadisonCRISPR-Cas9 gene-editing of human cells and tissues holds much promise to advance medicine, drug discovery and biology, but standard editing methods require weeks of reagent preparation where much of the initial edited samples are destroyed during analysis. Here, a new approach is described that separates thousands of edited cell populations for automated, live high-content analysis. The approach lowers the time and cost of gene editing and produces edited stem cells at high efficiencies. This preclinical platform adds important capabilities to observe editing and selection in situ within complex structures generated by human cells.

12:00 pm Talk Title to be AnnouncedSylvain Costes, Ph.D., Principal Investigator, Cancer and DNA Damage Response, Lawrence Berkeley National Laboratory

12:30 Drug Discovery Using Kinetic Live-Cell Imaging of Primary Human CellsEnrico Schmidt, Ph.D., Lab Head and Investigator, Center for Proteomic Chemistry, Integrated Lead Discovery, Novartis Pharma AGEngulfment of apoptotic cells is a highly dynamic process regulated by a complicated network of extra- and intracellular pathways. In order to identify modulators of this process with a broad molecular mode of action, dynamic live-cell imaging is required. We have developed a fully automated imaging assay to measure uptake of apoptotic corpses using primary human cells in a 1536 multi-well format that allows monitoring of the complete dynamic range of the process and identifying modulators.

PHENOTYPIC SCREENING IN iPSC AND PRIMARY CELL MODELS

10:55 Chairperson’s Remarks

11:00 Cardiac Regeneration: Influencing Proliferation and Fate Decision of Patient and iPS-Derived Cardiac Progenitors with Small MoleculesLauren Drowley, Ph.D., Associate Principal Scientist, AstraZenecaDespite the presence of cardiac progenitor cells, functional repair of the heart after injury is inadequate. Identification of signaling pathways involved in the proliferation and differentiation of cardiac progenitor cells (CPCs) will broaden insight into the fundamental mechanisms playing a role in homeostasis and disease and may provide strategies for in vivo regenerative therapies. We have developed 384-well phenotypic assays using iPS and primary human CPCs and identified novel compounds which are currently being followed up.

11:30 Using iPSC-Derived Cardiomyocytes for Biomarker and Drug DevelopmentUlrich Broeckel, M.D., Professor, Pediatrics, Medical College of WisconsinLeft ventricular hypertrophy (LVH) is one of the most potent risk factors for cardiovascular disease. On cellular and molecular levels, studying cardiomyocytes (CMs) as a main target cell can yield important insights into LVH pathophysiology. In this presentation we will discuss results from our disease modeling studies using patient-specific iPSC-derived cardiomyocytes to understand the inter-individual variation of disease risk. Furthermore, we will discuss the potential of patient-specific cell lines for biomarker development as well as the potential of iPSCs for drug development and testing. Our results should demonstrate the spectrum and power of iPSC-derived cells for disease modeling in complex cardiovascular diseases.

12:00 pm A Phenotypic Screen for Apolipoprotein E-Promoting Compounds in Human Primary AstrocytesTae-Wan Kim, Ph.D., Associate Professor, Department of Pathology & Cell Biology, Columbia University Medical CenterApolipoprotein E (apoE) is produced by astrocytes in the brain and is critically involved in the pathophysiology of Alzheimer’s disease (AD). Our phenotypic, high-throughput screening for small molecules of apoE enhancers in human primary astrocytes identified a number of apoE-enhancing hit compounds via previous unknown mechanisms, including regulators of cholesterol metabolism, GPCRs, neurotransmitter receptors and kinases. Our approach may yield useful tool compounds for mechanism studies or therapeutic leads for AD.

12:30 High-Content Image Analysis of Tissue Sections on SlidesBeatrice Knudsen, M.D., Ph.D., Director, Translational Pathology, Cedars Sinai Medical Center

FRIDAY, FEBRUARY 12

7:45 am Breakfast Presentation (Opportunity Available) or Morning Coffee

PHENOTYPIC DRUG DISCOVERY: LESSONS LEARNED8:25 Chairperson’s RemarksUlrich Schopfer, Ph.D., Novartis Institutes for BioMedical Research

8:30 Lessons from Phenotypic Lead DiscoveryUlrich Schopfer, Ph.D., Executive Director and Head, Integrated Lead Discovery, Novartis Institutes for BioMedical ResearchPhenotypic screening in in vivo or ex vivo models has been the historic origin of drug discovery. When advances in molecular biology enabled target-based screening, these origins lost popularity in favor of more reductionist approaches. Over the last several years, there has been a renaissance of phenotypic discovery approaches in academia and the pharmaceutical industry. It is time to take stock and assess the successes and the difficulties that were encountered. We will discuss the experience with phenotypic lead discovery at Novartis and look out to the integration of phenotypic and target-based approaches that we predict to be the strategy of the future.

9:00 High-Content Cell-Based Assays for Receptor Internalization and Intracellular TraffickingRegis Doyonnas, Ph.D., Senior Principal Scientist, High-Content Screening and HTS-Flow Cytometry, Primary Pharmacology Group, Pfizer

9:30 Know Your Target, Know Your MoleculeErik Hett, Ph.D., Team Leader, Senior Scientist, Chemical & Molecular Therapeutics, BiogenI will pose some key questions about the characteristics of protein targets and small-molecule drugs that may be important to consider in drug discovery projects and could improve prospects for future clinical success. This includes questions such as what is your target, where does it localize, does it have multiple isoforms, as well as, how does your molecule bind, where does it distribute, what are the consequences of it binding your target, and how much occupancy is required to drive your phenotype?


10:15 Coffee Break in the Exhibit Hall with Poster Viewing

HIGH-CONTENT ANALYSIS PHENOTYPIC SCREENING1:00 Luncheon Presentation (Sponsorship Opportunity Available) or Lunch on Your Own

HIGH-CONTENT SCREENING IN ANIMAL MODELS

1:55 Chairperson’s RemarksAndreas Vogt, Ph.D., University of Pittsburgh

2:00 High-Content Analysis and Multicellular Organisms in the Continuum of Quantitative Systems Pharmacology (QSP)Andreas Vogt, Ph.D., Associate Professor, Computational and Systems Biology, University of PittsburghQuantitative systems pharmacology (QSP) is an emerging drug discovery paradigm that aims to comprehensively understand the interaction of drugs across systems of increasing complexity and within the physiologic environment of the cell. An important part of QSP is the development and execution of clinically relevant discovery assays. I will present an example from zebrafish discovery to illustrate how high-content analysis impacts at different points of the QSP continuum.

2:30 Zebrafish-Based in vivo Screens for Selective Modulators of Developmental PathwaysCharles C. Hong, M.D., Ph.D., Associate Professor, Cardiovascular Medicine, Pharmacology, and Cell & Developmental Biology, Vanderbilt University School of Medicine

3:00 Discovering Small Molecule Neuro-Protectives through a Chemical Genetic Neurodegeneration Model in Larval ZebrafishSu Guo, Ph.D., Professor, Bioengineering and Therapeutic Sciences, University of California, San FranciscoNeurodegenerative disorders such as Alzheimer’s disease (AD) and Parkinson’s disease (PD) affect millions of people worldwide and are without cure. Here we report the assay development and a pilot screen for small molecule neuro-protectives employing a chemical genetic neurodegeneration model in larval zebrafish. We provide evidence that the neurodegeneration in this model is a result of oxidative stress and is necroptotic rather than apoptotic, mimicking neuronal loss in AD and PD. The compounds identified through our screen represent promising leads for future testing in preclinical and clinical settings.

3:30 Ultra-High-Content Screening of Live Parasitic WormsSteven Chi-Ming Chen, Specialist, Pharmaceutical Chemistry, Small Molecule Discovery Center at UCSF, Mission BayHCS has the potential to provide deep insight into drug treatments by capturing feature-rich time-lapsed images of live organisms. We have developed an HCS method using bright-field imaging to interrogate the larval stage of the flatworm Schistosoma mansoni, the etiological agent of the endemic disease Schistosomiasis. By quantifying multiple static and kinetic features, we are able to define complex phenotypes; we also demonstrate the use of this method for high-throughput screening.

4:00 Close of Conference

1:00 Luncheon Presentation (Sponsorship Opportunity Available) or Lunch on Your Own

ASSAY DEVELOPMENT FOR PHENOTYPIC SCREENING

1:55 Chairperson’s Remarks

2:00 Analysis of Cellular Heterogeneity in Phenotypic Assays: Application of Metrics for Assay Quality Control and Biological InterpretationMark Schurdak, Ph.D., Research Associate Professor, Computational and Systems Biology, University of Pittsburgh; Director, Drug Discovery InstituteHeterogeneity is an intrinsic feature of cell systems, and is often the result of deterministic regulatory molecular mechanisms. To take full advantage of information obtained from cytometric phenotypic assays and gain a deeper understanding of biological systems and their response to perturbagens, it is necessary to analyze the distribution of cellular phenotypes. We have established metrics to quantify the distribution of cellular responses. The metrics and methods developed are presented here as a workflow for analysis of heterogeneity in large-scale biology projects.

2:30 Cell Line Profiling and Target Identification of Nannocystin ANathan Ross, Ph.D., Senior Investigator, High Throughput Biology Group Leader, Novartis Institutes for BioMedical Research

3:00 Tools for MoA Determination and Pathway InterrogationFred King, Ph.D., Research Investigator, Novartis Institute for BioMedical Research

3:30 Phenotypic Screening to Identify Combination Drug Therapy for Infections Caused by Drug-Resistant Bacteria and Ebola VirusWei Zheng, Ph.D., Group Leader, Division of Preclinical Innovation, National Center for Advancing Translational Sciences, National Institutes of HealthHospital drug-resistant bacteria and recent Ebola infection are urgent medical incidences that lack effective therapeutics. We have used the phenotypic screening approach in a drug repurposing screen and identified several three-drug combinations that can effectively inhibit drug-resistant bacteria and Ebola virus.

4:00 Close of Conference


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