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 an offering of technology demonstrations and dinner courses.
1. HIGH-CONTENTANALYSIS
&PHENOTYPICSCREENING
Cambridge Healthtech Institute’s Thirteenth Annual
FEBRUARY 11 - 12, 2016 | HILTON SAN DIEGO RESORT & SPA | SAN DIEGO, CA
HighContentAnalysis.com
FEATUREDSPEAKERS
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. LansingTaylor
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
ExpertThinkTank: How to Meet the Need for
Physiologically Relevant Assays
THE ORIGINAL HIGH-CONTENT ANALYSIS EVENT
SAVE UP TO $
350
REGISTER BY NOVEMBER 13
2. 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 ofTechnology
• Mohanraj Dhanabal, Ph.D., Group Leader, Lead DiscoveryTechnology,
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 andTherapeutic 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., ActingTeam Lead, RNAi Screening Facility,
National Center for AdvancingTranslational 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 BiomarkerTeam 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 Vitro Strategies, LLC
• Mary-Ann Mycek, Ph.D., Professor and Associate Chair forTranslational
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, HighThroughput 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. LansingTaylor, 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 AdvancingTranslational Sciences, National
Institutes of Health
3. HighContentAnalysis.com | 3
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Sponsorship allows you to achieve your objectives before, during, and long
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Opportunity includes a 30-minute podium presentation. Boxed lunches are
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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
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in conference materials
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HOTEL & TRAVEL INFORMATION
Conference Venue and Hotel: Hilton San Diego Resort & Spa
1775 East Mission Bay Drive
San Diego, CA 92109
Phone: 619-276-4010
Reservations: Go to the travel page
of www.HighContentAnalysis.com
Discounted Room Rate: $185 s/d
Discounted Room Rate Cutoff Date: January 12, 2016
Go to the travel page www.HighContentAnalysis.com
for additional info
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4. 4 | HighContentAnalysis.com
HIGH-CONTENTANALYSIS PHENOTYPICSCREENING
HIGH-CONTENT ANALYSIS FOR
IMMUNOTHERAPY DEVELOPMENT
10:30 A Paradigm Shift in Immune Cell-Mediated Immuno-
Modulatory Responses Using High-Throughput FACS Analysis
Mohanraj Dhanabal, Ph.D., Group Leader, Lead DiscoveryTechnology, EMD Serono
11:00 High-Content Imaging Assays to Elucidate Antibody
Mediated Antigen Endocytosis
Ming Lei, Senior Scientist, Lead Discovery & Optimization, Bristol-Myers Squibb
Understanding 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 Profiling
Steven Rust, Senior Manager, R&D, MedImmune
12:00 pm Luncheon Presentation (Sponsorship Opportunity
Available) or Lunch onYour Own
3D CELLULAR MODELS (Cont.)
10:30 Label-Free Nonlinear Optical Microscopy for Non-Invasive
Viability Screening in 3D EngineeredTissues
Mary-Ann Mycek, Ph.D., Professor and Associate Chair forTranslational Research,
Biomedical Engineering, College of Engineering & Medical School, University of Michigan
Label-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 BioengineeringApproaches and High-ContentAnalysis Routines to
Characterize Heterogeneity andTreatment Response in 3DTumor Models
Imran Rizvi, Ph.D., Instructor, Medicine and Dermatology, Brigham and Women’s
Hospital, Massachusetts General Hospital, Harvard Medical School
Among 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 ProbeVarious Disease Pathologies
Madhu Lal-Nag, Ph.D., ActingTeam Lead, RNAi Screening Facility, National Center
for AdvancingTranslational Sciences, National Institutes of Health
Historically, 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 onYour 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 MODELS
8:00 Chairperson’s Opening Remarks
Anthony M. Davies, Ph.D., Center Director,Translational Cell Imaging Queensland (TCIQ), Institute of Health Biomedical Innovation, Queensland University ofTechnology
8:15TheTrials andTribulations of Complex Phenotypic Screening
Shane Horman, Ph.D., Research Investigator, Advanced Assays, Genomics Institute of the Novartis Research Foundation
With 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.
8:45The Challenges of Identifying Cellular Phenotypes in 3D in vitro Cellular Assay Systems
Anthony M. Davies, Ph.D., Center Director,Translational Cell Imaging Queensland (TCIQ), Institute of Health Biomedical Innovation, Queensland University ofTechnology
Currently, 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 Screening
The 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 ofTechnology
Separate registration required. Please visit www.HighContentAnalysis.com for further information.
5. HighContentAnalysis.com | 5
HIGH-CONTENTANALYSIS PHENOTYPICSCREENING
MACHINE LEARNING AND SYSTEMS BIOLOGY
APPLIEDTO HIGH-CONTENT SCREENING
1:25 Chairperson’s Remarks
Vance Lemmon, Ph.D., University of Miami
1:30 Rapid Deconvolution of PharmacologicalTargets for
Drug Discovery
Vance Lemmon, Ph.D., Professor and Chair, Developmental Neuroscience, The
Miami Project to Cure Paralysis, University of Miami
Target-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 LearningTools
David J. Logan, Ph.D., Computational Biologist, Imaging Platform, Broad
Institute of Harvard and MIT
Biologists 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 Imaging
Jeff Saucerman, Ph.D., F.A.H.A., Associate Professor, Biomedical Engineering,
University of Virginia
Biochemical 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.
3:00 Sponsored Presentation (Opportunity Available)
3:15 Refreshment Break in the Exhibit Hall with Poster Viewing
IMPLEMENTING PHENOTYPIC SCREENING
1:25 Chairperson’s Remarks
D. Lansing Taylor, Ph.D., University of Pittsburgh
1:30The Role of Phenotypic Screening in Quantitative Systems
Pharmacology (QSP)
D. LansingTaylor, Ph.D., Director, University of Pittsburgh Drug Discovery Institute
and Allegheny Foundation Professor, Computational and Systems Biology,
University of Pittsburgh
We 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: BringingTechnology to the Biology
Paul Andrews, Ph.D., Director, National Phenotypic Screening Centre, University of
Dundee, UK
Understanding 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 fromTarget ID to Profiling Cellular
Function in Early Stage Drug Discovery
Susanne Heynen-Genel, Ph.D., Director, High Content Screening Systems, Sanford
Burnham Prebys Medical Discovery Institute
Phenotypic 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.
3:00 Sponsored Presentation (Opportunity Available)
3:15 Refreshment Break in the Exhibit Hall with PosterViewing
ORGANOIDS AND 3D ORGANOTYPIC CELL CULTURE
4:00 Phenotypic Screening to Accelerate Lead Discovery and Drug Repositioning
Zhuyin Li, Ph.D., Translational Biomarker Team Lead, Lead Discovery & Optimization, Bristol-Myers Squibb
Potential 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 MimicTumor Microenvironment andTissue Architecture
Matthias Nees, Ph.D., Coordinator, HCSLab, Turku Science Park/Finland
5:00 High-Throughput Imaging: Focusing in on Cancer Drug Discovery in 3D
DanielV. LaBarbera, Ph.D., Associate Professor, Drug Discovery and Medicinal Chemistry, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado
High-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 Viewing
5:30 Short Course Registration
6:30-9:00 (SC2) DINNER EXPERTTHINKTANK: How to Meet the Need for Physiologically Relevant Assays
It 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, LLC
Separate registration required. Please visit www.HighContentAnalysis.com for further information.
6. 6 | HighContentAnalysis.com
HIGH-CONTENTANALYSIS PHENOTYPICSCREENING
INNOVATION IN HCA ASSAY DEVELOPMENT
10:55 Chairperson’s Remarks
Alan Waggoner, Ph.D., Carnegie Mellon University
11:00 Fluorescent Biosensors for Live Cell ProteinTrafficking
Alan Waggoner, Ph.D., Professor, Biological Sciences, and Director, Molecular
Biosensor and Imaging Center, Carnegie Mellon University
Live 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 Cells
Krishanu Saha, Ph.D., Assistant Professor, Biomedical Engineering, University
of Wisconsin, Madison
CRISPR-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 pmTalkTitle to be Announced
Sylvain 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 Cells
Enrico Schmidt, Ph.D., Lab Head and Investigator, Center for Proteomic
Chemistry, Integrated Lead Discovery, Novartis Pharma AG
Engulfment 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 Molecules
Lauren Drowley, Ph.D., Associate Principal Scientist, AstraZeneca
Despite 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 Development
Ulrich Broeckel, M.D., Professor, Pediatrics, Medical College of Wisconsin
Left 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 Astrocytes
Tae-Wan Kim, Ph.D., Associate Professor, Department of Pathology & Cell Biology,
Columbia University Medical Center
Apolipoprotein 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 ofTissue Sections on Slides
Beatrice 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 LEARNED
8:25 Chairperson’s Remarks
Ulrich Schopfer, Ph.D., Novartis Institutes for BioMedical Research
8:30 Lessons from Phenotypic Lead Discovery
Ulrich Schopfer, Ph.D., Executive Director and Head, Integrated Lead Discovery, Novartis Institutes for BioMedical Research
Phenotypic 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 IntracellularTrafficking
Regis Doyonnas, Ph.D., Senior Principal Scientist, High-Content Screening and HTS-Flow Cytometry, Primary Pharmacology Group, Pfizer
9:30 KnowYourTarget, KnowYour Molecule
Erik Hett, Ph.D., Team Leader, Senior Scientist, Chemical & Molecular Therapeutics, Biogen
I 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?
10:00 Sponsored Presentation (Opportunity Available)
10:15 Coffee Break in the Exhibit Hall with Poster Viewing
7. HIGH-CONTENTANALYSIS PHENOTYPICSCREENING
1:00 Luncheon Presentation (Sponsorship Opportunity Available)
or Lunch onYour Own
HIGH-CONTENT SCREENING IN ANIMAL MODELS
1:55 Chairperson’s Remarks
Andreas 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 Pittsburgh
Quantitative 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 Pathways
Charles 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 Zebrafish
Su Guo, Ph.D., Professor, Bioengineering and Therapeutic Sciences, University
of California, San Francisco
Neurodegenerative 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 Worms
Steven Chi-Ming Chen, Specialist, Pharmaceutical Chemistry, Small Molecule
Discovery Center at UCSF, Mission Bay
HCS 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 onYour 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
Interpretation
Mark Schurdak, Ph.D., Research Associate Professor, Computational and Systems
Biology, University of Pittsburgh; Director, Drug Discovery Institute
Heterogeneity 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 andTarget Identification of Nannocystin A
Nathan Ross, Ph.D., Senior Investigator, HighThroughput Biology Group Leader,
Novartis Institutes for BioMedical Research
3:00Tools for MoA Determination and Pathway Interrogation
Fred King, Ph.D., Research Investigator, Novartis Institute for BioMedical Research
3:30 Phenotypic Screening to Identify Combination DrugTherapy for
Infections Caused by Drug-Resistant Bacteria and EbolaVirus
Wei Zheng, Ph.D., Group Leader, Division of Preclinical Innovation, National Center
for AdvancingTranslational Sciences, National Institutes of Health
Hospital 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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February 11-12, 2016
Thirteenth Annual High-Content Analysis Second Annual Phenotypic Screening
CONFERENCE DINNER SHORT COURSES
One dinner short course $595 $295
Two dinner short courses $895 $495
February 10, 6:00-9:00 pm February 11, 6:30-9:00 pm
SC1: Introduction to High-Content Phenotypic Screening SC2: Expert ThinkTank: How to Meet the Need for Physiologically
Relevant Assays
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HIGH-CONTENTANALYSIS
&PHENOTYPICSCREENING
Cambridge Healthtech Institute’s Thirteenth Annual
FEBRUARY 11 - 12, 2016 | HILTON SAN DIEGO RESORT & SPA | SAN DIEGO, CA