Physiologically-Relevant Cell Models Congress

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Functional Analysis &
Screening Technologies
C O N G R E S S
C A M B R I D G E H E A L T H T E C H I N S T I T U T E ’ S S E C O N D A N N U A L
NOVEMBER 17-19, 2014 • HYATT BOSTON HARBOR • BOSTON, MA
NOVEMBER 17-18 NOVEMBER 18-19
Join 250+ R&D teams for practical discussions,
solutions and case studies for refining early-stage
drug discovery methods!
Phenotypic Drug
Discovery - Part I
Phenotypic Drug
Discovery - Part II
Engineering
Functional 3D Models
Screening & Functional
Analysis of 3D Models
Organotypic Culture
Models for Toxicology
Physiologically-Relevant
Cellular Tumor Models for
Drug Discovery
REGISTERBY
AUGUST22&
SAVEUPTO
$400!

2
Sunday, Nov. 16 Monday, Nov. 17 Tuesday, Nov. 18 Wednesday, Nov. 19
AM Phenotypic Drug Discovery - Part I
PM Phenotypic Drug Discovery - Part II
AM Engineering Functional 3D Models
PM Screening & Functional Analysis of 3D Models
AM Organotypic Culture Models for Toxicology
PM
Dinner Short Courses*
CONGRESS AT-A-GLANCE
ABOUT THE CONGRESS
Cambridge Healthtech Institute (CHI) is proud to release the final agenda for the 2nd Annual FAST: Functional
Analysis & ScreeningTechnologies Congress to be held on November 17-19, 2014 in Boston, MA. Join our
community of 250+ engineers, biologists, screening managers and pharmacologists dedicated to improving in vitro
cell models and phenotypic screening to advance drug discovery and development at six conferences, interactive
short courses, and in our exhibit/poster hall.
*Separate registration required
KEYNOTE SPEAKERS
Physiologically-Relevant
Cellular Tumor Models for Drug Discovery
George Church, Ph.D.,
Professor, Health Sciences and Technology, Harvard and MIT;
Founding Core Faculty Member, Wyss Institute for Biologically
Inspired Engineering, Harvard University
Anna Collén, Ph.D.,
Director, Reagents and Assay Development, AstraZeneca
Kristin Fabre, Ph.D.,
Scientific Program Manager, NCATS, National Institutes of
Health
Meir Glick, Ph.D.,
Head, In Silico Lead Discovery, Center for Proteomic Chemistry,
Novartis
Geraldine A. Hamilton, Ph.D.,
Senior Staff Scientist, Wyss Institute for Biologically Inspired
Engineering, Harvard University
Jing Li, Ph.D.,
Director, Genomics and Phenotypic Screening, Merck
Alan H. Wells, M.D., D.M.Sc.,
Vice Chair and Thomas J. Gill III Professor, Pathology, University
of Pittsburgh
John P. Wikswo, Ph.D.,
Founding Director, Vanderbilt Institute for Integrative Biosystems
Research and Education and Gordon A. Cain University
Professor, Biomedical Engineering, Vanderbilt University

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DINNER SHORT COURSES *
SUNDAY EVENING, NOV. 16
6:00-9:00 PM
(SC1) Introduction to 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 of Technology
(SC2) Exploring 3D Printing,
Bioinks and Scaffolds
The promise of 3D bioprinting to create human
tissues layer by layer is immense, ranging from
basic biological research to drug development and
testing, and ultimately to replacement organs.
However, organ and tissue structures vary in
complexity, and printing with living cells to create
tissues is much more complicated than printing 3D
objects in plastic.
Instructors:
Future Medical Applications in 3D Printing:
Clinical Benefits, Regulatory Issues and
Manufacturing Challenges
Michael Drues, Ph.D., President, Vascular Sciences
Multimaterial 3D Bioprinting
David Kolesky, Research Scientist, Jennifer Lewis
Laboratory, School of Engineering and Applied
Sciences and Wyss Institute for Biologically
Inspired Engineering, Harvard University
The Organovo 3D Bioprinting Platform:
Changing the Shape of Medical Research and
Practice
Deborah G. Nguyen, Director, R&D, Tissue
Applications, Organovo, Inc.
Additional Instructors to be Announced
MONDAY EVENING, NOV. 17
6:30-9:30 PM
(SC3) Stem Cell Models for Drug
Discovery
Instructors:
Induced Pluripotent Stem Cell-Based Disease
Models in Drug Discovery
Anne G. Bang, Ph.D., Director, Cell Biology, Prebys
Center, Sanford-Burnham Medical Research
Institute
Human Intestinal Epithelium Derived from
Induced Pluripotent Stem Cells
Pamela J. Hornby, Ph.D., Senior Scientific
Director and Research Fellow, Cardiovascular and
Metabolic Disease, Translational Models, Janssen
Pharmaceutical Companies of Johnson & Johnson
Application of Patient Neuronal Cells
Differentiated from iPS Cells as Disease Models
for Phenotypic Screening
Wei Zheng, Ph.D., Group Leader, National Center
for Advancing Translational Sciences, National
Institutes of Health
(SC4) Engineering Microfluidic Cell
Culture Chips
Microfluidic technology holds great promise for
the creation of advanced cell culture models.
Engineering a microfluidic cell culture chip to
emulate the dynamic physiology of a tissue’s
microenvironment is paramount for primary
cell culture and co-culture. As the availability of
functional human cell types for in vitro culture
increases, a microfluidic cell culture chip platform’s
potential to produce an in vitro system capable of
accurately reproducing acute and chronic human
responses to drug and pathological challenges in
real time will also increase.
Instructors:
The Basics of Integrating Cells with Microfluidic
Devices for Long-Term Cell Survival and
Function in Organ-on-a-Chip Devices
James J. Hickman, Ph.D., Professor, NanoScience
Technology, Chemistry, Biomolecular Science and
Electrical Engineering, University of Central Florida
Fabricating a LiverTissue Model in Microfluidic
Platforms
Rohit Jindal, Ph.D., Instructor, Surgery, Center for
Engineering in Medicine, Massachusetts General
Hospital
Additional Instructors to be Announced
TUESDAY EVENING, NOV. 18
6:00-9:00 PM
(SC5) 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
Panelists:
• Beverley Isherwood, Ph.D., Team Leader,
AstraZeneca R&D
• Michael Jackson, Ph.D., Senior Vice
President, Drug Discovery and Development,
Conrad Prebys Center for Chemical
Genomics, Sanford-Burnham Medical
Research Institute (tentative)
• Jean-Louis Klein, Ph.D., Principal Scientist,
Target and Pathway Validation, Platform
Technology and Science, GlaxoSmithKline
• Caroline Shamu, Ph.D., Director, ICCB-
Longwood Screening Facility and Assistant
Professor, Harvard Medical School
• D. Lansing Taylor, Ph.D., Director, University
of Pittsburgh Drug Discovery Institute
and Allegheny Foundation; Professor,
Computational and Systems Biology,
University of Pittsburgh
• Scott S. Verbridge, Ph.D., Assistant Professor,
School of Biomedical Engineering and
Sciences, Virginia Tech – Wake Forest
University
*Separate registration required. For further
information please visit FASTCongress.com.
Pre-Conference Webinar *
Tuesday, September 23
Future Medical Applications in 3-D Printing:
Clinical Benefits, Regulatory Issues &
Manufacturing Challenges TM
1:00-2:30 pm
Instructor: Michael Drues, Ph.D., President, Vascular Sciences
For further information please visit FASTCongress.com *Separate registration required
Gain Further Exposure:
Present a Poster and Save $50
• Your poster will be available to 250+
delegates
• You’ll automatically be entered into our
poster competition where two winners
each will receive an American Express
Gift Certificate
• $50 off your registration fee
• Your research will be seen by leaders
from pharmaceutical, biotech, academic
and government institutes
• Your research abstract will be published
in the conference proceedings
• Please visit FASTCongress.com for
poster instructions and deadlines

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Phenotypic screening (aka classical pharmacology) has been historically used in drug discovery. While technological developments have
made the prevalence of target-based screening more popular, statistical analysis shows that a disproportionate number of first-in-class
drugs with novel mechanisms of action come from phenotypic screening. Cambridge Healthtech Institute’s Second Annual Phenotypic
Drug Discovery 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.
Second Annual
Phenotypic Drug Discovery - Part I
Maximizing Information in Early Drug Discovery for Better Target and Drug Selection
NOVEMBER 17-18, 2014
SUNDAY, NOVEMBER 16
5:00 pm Short Course Registration and Main Conference Pre-
Registration
RECOMMENDED PRE-CONFERENCE SHORT COURSE*
6:00-9:00 (SC1) Introduction to High-Content Phenotypic
Screening
*Separate registration required. See page 3 for details.
MONDAY, NOVEMBER 17
7:30 am Conference Registration and Morning Coffee
CASE STUDIES IN PHENOTYPIC DRUG DISCOVERY
8:00 Chairperson’s Opening Remarks
Regis Doyonnas, Ph.D., Pfizer
8:10 Phenotypic Drug Discovery Advances toward
Pharmacological ChaperoneTherapies
Regis Doyonnas, Ph.D., Senior Principal Scientist, High-Content Screening and
HTS-Flow Cytometry, Hit Discovery and Lead Profiling, Worldwide Research &
Development, Pfizer
Pharmacological chaperones correct the proper folding of misfolded proteins
protecting them from degradation and allowing them to correctly localize within
the cell. For many years, drug discovery assays have focused on direct binding
of pharmacological chaperones to their protein targets. The relative success
of this approach has been called to question with the increasing discussion
and analysis of the merits of phenotypic screening. While pharmacological
chaperone assays may not lend themselves as “canonical” phenotypic screens,
i.e., an assay for direct disease associated outcomes, a case can be made
that broadening the analysis to a biological read-out resulting from chaperone
activities within a cellular environment would reflect more of the pertinent
biology of the system and thus increase our level of confidence in translation
to patients.
»»KEYNOTE PRESENTATIONS
8:35 Phenotypic Screening: A New Perspective
Jing Li, Ph.D., Director, Genomics and Phenotypic Screening, Merck
Research Laboratories
Two general approaches of drug discovery, either target-centric or
phenotypic, are usually taken. Interestingly, in the first-in-class drug
category, the phenotypic approach yielded more approved drugs than
the target-centric approach during the period 1999-2008. The lack of
chemistry support and the immaturity of technology platforms for protein
target identification have contributed to the low success rate for past
phenotypic screens. Recent advances in the fields of affinity capture,
quantitative mass spectrometry, and chemoinformatics greatly improve
our chances to identify the underlying protein targets. This provides
us opportunities to revisit this subject. With the lessons learned, the
possibility of successfully applying phenotypic screens in drug discovery
can improve significantly.
9:00 Phenotypic Discovery at AstraZeneca
Anna Collén, Ph.D., Director, Reagents and Assay Development,
AstraZeneca R&D, Mölndal, Sweden
A key denominator for successful phenotypic screening is the
translational link of the in vitro cell systems and assays to eventually
mimic human physiology. This will direct the positive outcome of the
phenotypic screen and enable target identification of relevance to
drug discovery. We will present how we at AstraZeneca have worked
with phenotypic discovery in different areas: neuroscience with ApoE
phenotypic screen, regenerative medicine, cardiac regeneration, islet
health and finally identification with factors that differentiate white
adipocytes to “brownish.”
9:25 Identification and Optimization of a Novel Phenotype
Screen Hit to the First-in-Class HCV NS5A Inhibitor Daclatasvir
Makonen Belema, Ph.D., Principal Scientist, Virology Chemistry, Bristol-Myers
Squibb
High-throughput screening of the BMS compound collection afforded a
mechanistically unique thiazolidinone hit exhibiting a sub-micromolar inhibitory
potency towards an HCV replicon. Raising and mapping of resistance mutation
indicated that the NS5A protein, a key protein with a multifunctional role in the
virus’ replication cycle, was the most likely target. Highlights of the medicinal
chemistry campaign that optimized this screen hit to the highly potent first-
in-class HCV NS5A inhibitor daclatasvir along with key clinical results will
be discussed. In addition, aspects of the mechanistic study that not only
corroborated target engagement but also resulted in the discovery of a class of
NS5A-targeting molecules that synergize the inhibitory potency of daclatasvir
toward resistant mutants will be covered.
9:50 Sponsored Presentation (Opportunity Available)
10:05 Coffee Break in the Exhibit Hall with Poster Viewing
10:35 Factors Important to a Successful Phenotypic Screening
Strategy
David C. Swinney, Ph.D., CEO, Institute for Rare and Neglected Diseases
Drug Discovery (iRND3)
Phenotypic assays are essential tools for drug discovery, with different
endpoints depending on the goals: 1) empirical endpoints to understand the
underlying biology, 2) empirical endpoints to identify toxicity of drug candidates,
and 3) knowledge-based endpoints (biomarkers) to guide discovery which
are ideally translational. The value of phenotypic assays is increased through
effective alignment of phenotypic assay endpoints with the objectives of the
relevant R&D stage.
11:00 Heterogeneity in Drug Discovery, Development and
Diagnostics
D. Lansing Taylor, Ph.D., Director, University of Pittsburgh Drug Discovery
Institute and Allegheny Foundation Professor, Computational and Systems
Biology, University of Pittsburgh
11:25 Integrating NovelTechnologies to Identify Small Molecules
that DriveTranslational Research andTherapeutics
Michelle Palmer, Ph.D., Co-Director, Center for the Development of
Therapeutics, Broad Institute of Harvard and MIT
Advances in human genetics have lead to new drug discovery strategies that
may lower the rate of attrition when translated to human trials. Molecular
characterization of patient-derived samples is providing new insights into the
root cause of many diseases. Many of these insights point to targets that have
traditionally been challenging for small-molecule therapeutics. Identification of
drugs to modulate targets where knowledge of the function in disease is poorly
understood and processes such as disruption of these novel targets require

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innovation in chemistry, phenotypic cell-based assays and target identification
studies. At the Broad Institute, we have integrated technology across all aspects
of lead identification in an effort to realize the benefit of the genes to drugs
approach in multiple disease areas including psychiatric disease. Examples
that illustrate the application of novel targets and pathways in a phenotypic
screening approach will be presented.
11:50 Close of Session
12:00 pm Luncheon Presentation: Sponsored by
Phenotypic Screening of Compounds and Drug
Combinations in BioMAP® Oncology Systems
Reveals Divergent Effects on Clinically-Relevant Biomarkers
Scott Pattison, Ph.D., Director, Business Development, DiscoveRx,
BioSeek Division
BioMAP® Oncology Systems model host-tumor microenvironments using
human primary fibroblasts or endothelial cells co-cultured with PBMC and
select cancer cell lines. The signaling environment modeled therein significantly
impacts drug activity on clinically relevant biomarkers. Consistent with clinical
reports, we detect enhanced activities with the combination of Dabrafenib
(BRAF inhibitor) and Trametinib (MEK inhibitor) as compared to the respective
monotherapies. BioMAP® oncology systems provide a predictive human model
to assess therapeutic strategies prior to clinical testing.
HIGH-CONTENT ANALYSIS
1:30 Chairperson’s Remarks
Anne E. Carpenter, Ph.D., Broad Institute of Harvard and MIT
1:35 Advancing Drug Discovery through the Application of High-
Content Phenotypic Profiling
Beverley Isherwood, Ph.D., Team Leader, AstraZeneca R&D
High-content analysis (HCA) has developed into an important platform for
drug discovery. We describe approaches taken at AstraZeneca to develop and
implement multiparametric high-content assay panels in physiologically-relevant
models of disease to identify and validate targets, predict toxic liability and
characterize compound mode of action. We discuss the tools and workflows
adopted to facilitate the efficient, consistent and reliable application of HCA at
multiple stages of drug discovery.
2:00 High-Content Imaging Workflows for Screening and Assay
Development in Oncology Drug Discovery
Joern Hopke, Ph.D., Senior Research Investigator, Sanofi
High-content imaging and phenotypic screening create distinctive challenges
for data management and subsequent data analysis. We have assembled an
array of data management, processing and analysis tools into efficient and
flexible workflows for large-scale HCS and small-scale assay development alike.
Examples of a screening campaign with successive multivariate data analysis
for compound MOA deconvolution and a number of phenotypic 3D assays
relevant to oncology drug discovery will be presented.
2:25 Advancing Phenotypic Drug Discovery in Cancer through
Combined High-Content Imaging and Reverse Phase Protein
ArrayTechnology
Neil Carragher, Ph.D., Principal Investigator, Edinburgh Cancer Research UK
Centre, University of Edinburgh
Limited understanding of drug mechanism-of-action and pharmacological
resistance contributes to poor efficacy and attrition at later stages of drug
discovery and development. We demonstrate how multiparametric high-
content imaging and Reverse Phase Protein Microarray (RPPA) technologies
can combine to enable a robust and unbiased approach to profiling compound
mechanism-of-action and optimizing efficacy within complex in vitro and in vivo
settings. We will provide case studies demonstrating how we have applied
these technologies to advanced models of cancer to progress new chemical
entities identified initially as hits from phenotypic screens towards late-stage
preclinical development.
3:05 Refreshment Break in the Exhibit Hall with Poster Viewing
3:45 Discovering Unexpected Phenotypes Using Image-Based
Profiling
Anne E. Carpenter, Ph.D., Director, Imaging Platform, Broad Institute of
Harvard and MIT
Microscopy images contain rich information about the state of cells, tissues and
organisms. Our laboratory is extracting patterns of morphological perturbations
(“signatures”) from images in order to identify similarities between various
chemical or genetic treatments. Our goal is to classify drug mechanisms
of efficacy and toxicity, distinguish cancer-relevant proteins, and identify
biomarkers of disease. We hope to make perturbations in cell morphology as
computable as other large-scale functional genomics data.
4:10 Advances in Phenotypic HTS Reporter Assays and
Opportunities for Underserved Disease
James Inglese, Ph.D., National Center for Advancing Translational Sciences,
National Institutes of Health
Emerging sophistication in assays developed to model pathogenic pathways
has the potential to reveal new insights regarding possible routes to
pharmacological intervention and in some cases directly to clinical candidates
from the repositioning of approved drugs. Specific examples from my lab at NIH
focused on assay development and high-throughput screening will be discussed
to illuminate these ideas in the context of disease foundation-sponsored
collaborative partnerships.
4:35The Implementation of Phenotypic Cell-Based Assays and
High-Content Imaging inTranslational Research: Choosing the
RightTools for the Job
Anthony M. Davies, Ph.D., Center Director, Translational Cell Imaging
Queensland (TCIQ), Institute of Health Biomedical Innovation, Queensland
University of Technology
5:15 Welcome Reception in the Exhibit Hall with Poster Viewing
6:15 Short Course Registration
RECOMMENDED DINNER SHORT COURSE*
6:30-9:30 (SC3) Stem Cell Models for Drug Discovery
TUESDAY, NOVEMBER 18
8:00 am BreakfastTechnology Showcase (Sponsorship
Opportunities Available) or Morning Coffee
PHENOTYPIC DRUG DISCOVERY
This showcase provides an opportunity for sponsoring companies
to showcase their new and emerging technologies for phenotypic
screening, including novel assays, high-content and imaging
technologies, physiologically-relevant cellular models and data
analysis tools.
8:00 Showcase #1
8:20 Showcase #2
8:40 Showcase #3
COMPLEX PHYSIOLOGICALLY-RELEVANT CELLULAR
MODELS FOR PHENOTYPIC DRUG DISCOVERY
Michael Jackson, Ph.D., Sanford-Burnham Medical Research Institute
9:05 Use of Patient-Derived Cells in Disease-in-a-Dish Phenotypic
Screens
Michael Jackson, Ph.D., Senior Vice President, Drug Discovery and
Development, Conrad Prebys Center for Chemical Genomics, Sanford-
Burnham Medical Research Institute
Reprogramming of somatic cells to induced pluripotent stem cells (iPSC) has
enabled a new paradigm in drug discovery that leverages disease-in-a-dish
phenotypic screens. Technical challenges in the scalability and reproducibility
of assays based on iPS (patient) cells remain a major hurdle in executing
such screens, especially where mature differentiated cell types are required.
Progress on the use of this approach to identify drugs (repurposed) to treat
genetic disease will be presented.
9:30 Phenotypic Screening for Alzheimer’s Disease Drug
Discovery in Stem Cell-Derived and Primary Brain Cells
Tae-Wan Kim, Ph.D., Associate Professor, Pathology and Cell Biology,
Columbia University Medical Center
The development of effective and safe therapeutics for complex
neurodegenerative diseases, such as Alzheimer’s disease (AD) is hampered
in part by lack of physiological cell models. We will discuss our progress on
phenotypic, high-throughput screening platforms targeting key AD-relevant
cellular pathways (i.e. tau, amyloid and apoE) in primary and stem cell-derived

6
Second Annual
Phenotypic Drug Discovery - Part II
Maximizing Information in Early Drug Discovery for Better Target and Drug Selection
12:00 pm Conference Registration
PHENOTYPIC SCREENING OF 3D MODELS
Aron Jaffe, Ph.D., Novartis Institutes for BioMedical Research
1:35 Developing and Utilizing 3D Culture Systems for Novel
Target Discovery
Aron Jaffe, Ph.D., Senior Investigator, Developmental and Molecular
Pathways, Novartis Institutes for BioMedical Research
Target identification and validation have historically relied on immortalized or
tumor cell lines grown on plastic. Recent techniques involving growth of cells
in three-dimensional matrices have enabled modeling of cellular processes
in an environment that more closely resembles the in vivo setting. This
presentation will highlight the strategies for designing complex cellular assays
for target discovery using medium and high-throughput screening methods in
three dimensions.
2:00 3D versus 2D: Insight from Pharmacology and Genomics
Jean-Louis Klein, Ph.D., Principal Scientist, Target and Pathway Validation,
Platform Technology and Science, GlaxoSmithKline
2:30Technology Showcase (Sponsorship Opportunities
Available)
3D CELLULAR MODELS FOR DRUG AND
TARGET SCREENING
This showcase provides an opportunity for sponsoring companies to
showcase their new and emerging 3D cell models and technologies
for the next generation of drug and target phenotypic screening.
2:30 High-Throughput Compatible Co-Spheroid
Model Analyzing Compound Effects on
BothTumor and Stroma Cells
Sponsored by
Jan E. Ehlert, Ph.D., Head, Cellular Drug
Discovery, ProQinase GmbH
A spheroid-based co-culture system for the simultaneous analysis
of compound effects on the proliferation of tumor as well as of
stroma cells was established. The modular HTS-compatible system
reveals results reflecting cell-specific drug susceptibility and
cell/cell interactions.
2:50 Showcase #2
3:10 Showcase #3
HIGH-CONTENT ANALYSIS OF TUMOR SPHEROID MODELS
David Nolte, Ph.D., Professor, Physics, Purdue University; President, Animated
Dynamics, Inc.
4:30 Drug Discovery and Development of Novel Anticancer
Agents: Applications of Novel 3D MulticellularTumor Spheroid
Models
Daniel V. LaBarbera, Ph.D., Assistant Professor, Drug Discovery and Medicinal
Chemistry, The Skaggs School of Pharmacy and Pharmaceutical Sciences, The
University of Colorado
Aberrant regulation of epithelial-mesenchymal transition (EMT) is a driving
force in the most prominent human diseases. In particular, EMT-driven tumor
progression promotes the expansion of cancer stem cells, drug resistance, and
the mesenchymal phenotype, which is invasive with a high metastatic potential.
Therefore, one therapeutic strategy to prevent metastatic dissemination is to
develop small molecule drugs that can revert the mesenchymal phenotype to
the more benign epithelial state. Using novel 3D multicellular tumor spheroid
(MCTS) models of EMT, suitable for high-throughput and high-content screening
(HTS/HCS), we have identified lead compounds that block TCF-transcription,
which regulates the mesenchymal phenotype in colorectal cancer.
4:55 Novel StromalTargets that SupportTumor Spheroid
Formation
Shane R. Horman, Ph.D., Research Investigator, Advanced Assay Group,
Genomics Institute of the Novartis Research Foundation
The stroma of solid organ tumors influences all phases of tumor progression
indicating that environment may be dominant to the genetics of cancer cells.
To expand these concepts to early stage drug discovery we have scrutinized
the interactions between colon stroma and colorectal carcinoma (CRC) cells
in a high-content co-culture 3D spheroid screen. Subsequently we were
able to identify novel fibroblast genes that, when depleted, abrogate CRC
spheroid formation revealing an extended chemotherapeutic space by which to
target tumors.
5:20 Developing Biodynamic Screening Assays for 3D Live-Tissue
Models
Dynamics, Inc.
Biodynamic screening performs three-dimensional functional imaging of
living tissue by measuring drug-induced changes in intracellular dynamics.
neurons and glial cells. Our approach will facilitate preclinical discovery of
promising therapeutic lead molecules for AD drug discovery.
10:45 Human Bronchial Epithelial Cells as a Phenotypic Model in
Cystic Fibrosis Drug Discovery
Tim Young, Ph.D., Research Fellow, Vertex Pharmaceuticals
Cystic fibrosis (CF) is caused by mutations in the CFTR gene, which result
in decreased ion and fluid transport across bronchial epithelium. Human
bronchial epithelial (HBE) cells grown in culture at an air-liquid interface retain
the phenotype of airway epithelium with respect to ion and fluid transport, and
mucociliary biology. HBEs derived from subjects with CF are impaired in these
functions and offer a phenotypic model to develop CFTR modulators.
11:10 Zebrafish Phenotypic Discovery for Small Molecules that
Augment Kidney Regeneration
Andreas Vogt, Ph.D., Associate Professor, Computational and Systems
Biology, University of Pittsburgh
Kidney regeneration after acute injury (AKI) is limited by formation of fibrotic
scar tissue. Through zebrafish phenotypic screening we identified small
molecules that prevent scarring and augment kidney regeneration after injury.
Transcriptional profiling suggested a cellular mechanism involving aberrant cell
cycle progression, which was confirmed experimentally in zebrafish and mice.
The data illustrate the utility of a zebrafish quantitative systems pharmacology
approach to discover new potential treatments for AKI.
11:35 Cancer Drugs on the Fly:Whole-Animal Chemical
Screening in Drosophila Identifies Drug Interactions with Stem
Cells, Stem CellTumors and the Stem Cell Microenvironment
Michele Markstein, Ph.D., Assistant Professor, Biology, UMass Amherst
Here we report the development of an in vivo chemical screening platform
using tumor models in the adult Drosophila intestine to study the interaction
of stem cells with drugs. Strikingly, we find that some FDA-approved
chemotherapeutics that can inhibit the growth of Drosophila stem cell tumors
can paradoxically promote the hyper-proliferation of their wild type counterparts.
These results reveal an unanticipated side effect on stem cells that may drive
tumor recurrence. We show that this side effect is mediated by the stem
cell microenvironment, which we demonstrate responds to a wide spectrum
of chemotherapy drugs. We propose that the same side effect may occur in
humans based on our finding that it is driven by the evolutionarily conserved
JAK-STAT pathway. To identify additional compounds that can inhibit tumors
without inducing side effects on the stem cell microenvironment, we screened
a library of 6,100 small molecules, from which we report the identification of
10 compounds that inhibit tumors without inducing the growth promoting side
effect. Altogether, our results highlight the importance of using in vivo models
to study the effects of drugs on stem cells: we show that the impact of a
chemotherapy drug on the stem cell microenvironment is just as important as
its impact on the stem cell itself.
12:00 pm Close of Phenotypic Drug Discovery - Part I Conference

FASTCongress.com 7
It is compatible with many 3D tissue formats, including tumor spheroids
grown in bioreactors or in multiwell plates, as well as tissue biopsies and
other organotypic models. Dynamics-based phenotypic profiling of tissues
provides a new type of high-content screening. This talk presents 3D assays
being developed for chemosensitivity and resistance, proliferation and
toxicity screening.
5:45 Close of Day
6:00-9:00 (SC5) ExpertThinkTank: How to Meet the Need for
Physiologically-Relevant Assays?
WEDNESDAY, NOVEMBER 19
7:30 am Breakfast Presentation (Sponsorship Opportunity Available)
or Morning Coffee
PHENOTYPIC DATA ANALYSIS AND MODELING
Caroline Shamu, Ph.D., Director, ICCB-Longwood Screening Facility and
Assistant Professor, Harvard Medical School
8:10 Cellular Assays for Cancer Pharmacology
A major goal of the Harvard Medical School Library of Integrated Network-
based Cellular Signatures (LINCS) Center is to collect and disseminate the
data and analytical tools needed to understand how human cells respond to
perturbations created by exposure to drugs. Our center has developed assays to
systematically query cell responses to kinase inhibitors and tools to analyze and
visualize the results.
»»KEYNOTE PRESENTATION
8:35 In silico Lead Finding through Holistic Understanding
of Screening Data from Multiple Approaches
Meir Glick, Ph.D., Head, In Silico Lead Discovery – Cambridge, Center
for Proteomic Chemistry, Novartis Institutes for BioMedical Research
The changing drug discovery environment presents a richer, more
complicated and novel data landscape. How can state of the art data
analytics increase the probability of a lead compound to be disease
relevant? We will discuss how in silico approaches actively shape the
lead discovery process: informing on relevant assays, compounds
subset design to probe the biology, visualization of complex biological
data, models elucidating target/MOA hypothesis and design of
chemical matter.
9:00 Big DataTools for High-Content Screens
Rajarshi Guha, Ph.D., Research Informatics Scientist, Center for Translational
Therapeutics, National Institutes of Health
In this talk I will provide an overview of the Hadoop ecosystem, an
infrastructure designed for parallel processing of large datasets. Specifically,
I will focus on the use of the Mahout library that enables large-scale machine
learning on top of Hadoop for the clustering of cell-level data from high-content
RNAi screens. I will then describe a backend infrastructure that links HBase, a
relational database layer on top of Hadoop, with a traditional Oracle data store
to explore and visualize the cell-level clustering.
10:50 Automated Learning of Perturbation Models
Robert F. Murphy, Ph.D., Ray and Stephanie Lane Professor of Computational
Biology and Professor of Biological Sciences, Biomedical Engineering and
Machine Learning; Director, Lane Center for Computational Biology, Carnegie
Mellon University
Traditional HCS methods detect perturbed phenotypes but do not allow
identification of the specific changes in cell organization underlying them;
results also cannot be easily compared across different HCS systems. We
developed methods to convert images into models of cell components and
how perturbagens affect them, and have also demonstrated that active machine
learning can build models of the effects of many drugs on many targets without
exhaustive experimentation.
11:15 An Evolutionary Dynamics Approach to StudyingTumor
Resistance
Arijit Chakravarty, Ph.D., Director, Modeling and Simulation, Takeda
Pharmaceuticals
11:40Towards Open Source Software for High-Content Screening
and Phenotypic Data Analysis
Frans Cornelissen, Principal Scientist, Translational Informatics, Janssen
Pharmaceutical Companies of Johnson & Johnson
A crucial step towards efficient mining of HCS data is the availability of a robust
platform for HCS data management and (semi-)automatic cellular phenotype
identification and classification. However, for many small and medium-size
screening groups, commercial software may be too expensive. We are in the
process of making our internally developed Phaedra software available as an
open source product. Examples will be presented to show that Phaedra is a
sound foundation that can be used as an integrated pattern recognition and
machine learning environment for HCS.
12:05 Genome-Wide RNAi-Compound Epistasis to Elucidate
Drug Pathways
Jeremy L. Jenkins, Ph.D., Senior Investigator, Developmental and Molecular
Pathways, High-Throughput Biology, Novartis Institutes for BioMedical
Research
Following phenotypic compound screening, target elucidation remains a
bottleneck for follow-up. We investigate examples of genome-wide siRNA
screening in the presence of sensitizing compound doses in order to find nodes
that sensitize or suppress drug activity and map ‘compound-effect’ pathways.
Epistatic shifts in drug activity are observed by intended target knockdown as
well as siRNA off-target knockdown caused by miRNA-like polypharmacology of
unintended siRNA seed sequence binding to mRNA 3’UTRs.
12:30 pm Close of Phenotypic Drug Discovery - Part II Conference
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8
Functional 3D models have quickly captured the attention of the pharmaceutical industry. All agree these 3D models offer high content,
high impact and high value. However, for wider implementation in R&D drug testing and screening labs, compatible higher-throughput
3D model platforms must be engineered to carry out research on the scale appropriate for drug discovery. Creating these more
biologically relevant models requires a multidisciplinary approach and multidisciplinary expertise. Cambridge Healthtech Institute’s Third
Annual Engineering Functional 3D Models meeting weaves together engineers, biologists, screening managers and pharmacologists.
As with any model, each specialty provides insights into the complete system advancing drug discovery and development.
Third Annual
Engineering Functional 3D Models
New Dimensions in the Dynamic Interaction between Drugs and Disease
SUNDAY, NOVEMBER 16
Registration
6:00-9:00 (SC2) Exploring 3D Printing, Bioinks and Scaffolds
MONDAY, NOVEMBER 17
8:15 Welcome and Chairperson’s Opening Remarks (Sponsorship
Opportunity Available)
»»KICKOFF KEYNOTE PRESENTATION
8:25 Personalized Reading and Writing of Organs
George Church, Ph.D., Professor, Genetics, Harvard Medical
School; Professor, Health Sciences and Technology, Harvard and
MIT; Founding Core Faculty Member, Platform Lead, Synthetic
Biology, Wyss Institute for Biologically Inspired Engineering, Harvard
University
We need better systems for testing small molecule, protein and
nucleic acid therapeutics—ideally personalized organs, as can be
achieved via iPSC, ePSC or SCNT-ESCs. One or more variants of
unknown significance can be tested for a causal role by using CRISPR
genome editing and a variety of simple cell types and complex organs
and systems derived by epigenomic reprogramming. This engineering
system is especially useful in leveraging the world’s only open-access
(with very well-characterized -omic and medical data) human subjects
(personalgenomes.org). The faithfulness of the organ system models,
as well as their drug responses, can be checked using fluorescent in
situ sequencing (FISSEQ).
ENGINEERING TISSUE CHIPS
AND INTEGRATING ORGAN SYSTEMS
9:05 Models of Complex Human Disease in 3D Skin-LikeTissues
Jonathan Garlick, D.D.S, Ph.D., Professor, Oral Pathology, School of Dental
Medicine, Tufts University; Director, Center for Integrated Tissue Engineering
and Professor, Tufts School of Medicine, School of Engineering and Sackler
School of Graduate Biomedical Sciences
Chronic diseases like diabetes are characterized by complex microenvironments
in which disease complications arise. The screening of novel treatments,
like chronic wounds, must use 3D tissue platforms that better mimic in vivo
conditions. We describe the development of 3D tissues that mimic non-healing
wounds by incorporating cells derived from chronic wounds and iPSCs. This
provides “disease in a tissue” platforms that can more efficiently translate in
vitro findings into clinical applications.
9:35Toward a 3D Model of Human Brain Development for
Studying Gene/Environment Interactions
Helena Hogberg, Ph.D., Research Associate, Environmental Health Sciences,
Bloomberg School of Public Health, Johns Hopkins University
Microphysiological systems (MPS) could generate more complex in vitro
human models that better simulate organ biology and function. iPSCs allow
cellular studies of individuals with different genetic backgrounds. Application
of iPSCs from different donors in MPS improves understanding of disease
mechanisms, drug development, toxicology and medicine. For a brain-on-a-
chip, we established a 3D model from healthy and Down Syndrome donors’
iPSCs with mRNA and microRNA levels evaluated during eight weeks of
neural differentiation.
10:30 “Body-on-a-Chip”: A Multi-Organ Microdevice for Drug
Development
Michael L. Shuler, Ph.D., Professor, Chemical Engineering and Chair,
Biomedical Engineering, School of Chemical and Biomolecular Engineering,
Cornell University
Our goal is the development of a human-based in vitro system that reduces
dependency on animal testing and makes more effective predictions of human
response to drugs. By combining microfabrication and cell culture, we have
constructed devices known as “Body-on-a-Chip” systems. These devices are
physical replicas of a physiologically based pharmacokinetic (PBPK) model
where tissue-engineered constructs replace the differential equations for each
organ in the PBPK.
11:00 Organs on a Chip:The Future of Personalized Medicine?
Kevin E. Healy, Ph.D., Jan Fandrianto Distinguished Chair in Engineering;
Professor and Chair, Bioengineering; Professor, Materials Science and
Engineering, University of California, Berkeley
Drug safety and efficacy testing are hampered by high failure rates attributed
to reliance on non-human animal models. We have developed integrated in
vitro models of human cardiac and liver tissue based on normal and patient-
specific hiPS cell populations differentiated into cardiomyocytes or hepatocytes,
respectively. Our in vitro integrated physiological system has the potential to
significantly reduce both the cost and duration of bringing a new drug candidate
to market.
12:00 pm Close of Session
12:15 Luncheon Presentation (Sponsorship Opportunity Available)
or Enjoy Lunch onYour Own
HIGH-DIMENSIONAL TISSUE AND ORGAN MODELS:
ADVANTAGES AND DISADVANTAGES OF 2D VS. 3D
Rosemarie Hunziker, Ph.D., Director, Tissue Engineering and Regenerative
Medicine, National Institute of Biomedical Imaging and Bioengineering,
1:35 2D Versus 3D:When to Make the Switch
Christopher S. Chen, M.D., Ph.D., Professor, Biomedical Engineering, Boston
University and Wyss Institute for Biologically Inspired Engineering, Harvard
University
The structure, mechanics and dimensionality of an extracellular matrix have
fundamental effects on the phenotype of mammalian cells. This presentation
examines how these physical cues can drive cell signaling and function, and
how we can use these insights to develop in vitro cultures that better mimic in
vivo biology for both discovery and development applications.

FASTCongress.com 9
2:05 Customized 3D Cell Cultures and
Assays Showcase (Sponsorship Opportunities Available)
All agree that 3D cell models that are morphologically and
functionally similar to native tissue hold the potential to improve in
vitro cell-based assays. However, it is important to note that there
is no one-size-fits-all solution; each cell type requires a different
environment and different assays to screen them. This session
showcases companies that are driving cell culture and screening
assays into the new dimension of studying health vs. disease and
drug response.
2:05 Showcase #1
2:25 Showcase #2
2:45 Showcase #3
3:45 Organs-on-Chips to Screen for Drug Efficacy and
Toxicity
Kristin Fabre, Ph.D., Scientific Program Manager, NCATS, National
The Microphysiological Systems Program, comprised of an MPS
Consortium of academic and government entities, aims to bioengineer
platforms (or chips) that mimic human organ systems. These platforms
help predict efficacy and toxicity of candidate compounds faster,
cheaper and with fewer animal models than current methods. The
project’s goal is to incorporate human iPSC-derived cell sources
(inducible pluripotent stem cells) into corresponding organ modules
and create an integrated Human-on-a-Chip to study drug response
within human bodies.
4:30 Organs-on-Chips: Highly Functional
Microphysiological Systems to Predict Human Physiology
and Pathobiology
Geraldine A. Hamilton, Ph.D., Senior Staff Scientist, Wyss Institute
for Biologically Inspired Engineering, Harvard University
This presentation focuses on our novel biomimetic microsystem
technologies and their potential application in predicting efficacy,
safety and mechanism of action for new drugs, chemicals and
cosmetics. Human organs-on-chips provide exciting new approaches
to attack fundamental questions in biology and develop smart
in vitro surrogates. This technology also offers a more human-
relevant alternative to current animal-based approaches for disease
model development.
6:30-9:30 (SC4) Engineering Microfluidic Cell Culture Chips
or Morning Coffee
TISSUE MICROENGINEERING TOOLS
Jonathan Garlick, D.D.S, Ph.D., Tufts University
8:35 Microengineering Hydrogels forTissue Engineering
Applications
Nasim Annabi, Ph.D., Instructor, Brigham and Women’s Hospital and Harvard
Medical School
Micro- and nanoscale technologies are powerful techniques in addressing the
current challenges in tissue engineering. These technologies have allowed
for an unprecedented ability to control cell-microenvironment interactions.
Our group has been actively involved in merging advanced biomaterials and
microscale technologies to create 3D vascularized tissues. I outline our work in
the development of microscale hydrogels to modulate cell-microenvironment
interactions for tissue engineering applications.
9:05 Development of 3DTissue Engineering Platforms for
Personalized CancerTherapeutics
Jenny Zilberberg, Ph.D., Assistant Scientist, The John Theurer Cancer Center,
Hackensack University Medical Center
I present work on the development of a novel 3D tissue engineering platform
that uses microfluidic technology to provide a physiologically relevant in vitro
model to study cancers that reside in or metastasizes to the bone/bone marrow
microenvironment, and could offer a suitable tool to perform chemosensitivity
analysis and develop new cancer therapeutics.
9:35 Micro- and Nanoscale 3D Bioprinting for FunctionalTissue
Scaffolds
Shaochen Chen, Ph.D., Professor, NanoEngineering and Bioengineering,
University of California, San Diego
I discuss my laboratory’s recent research efforts in femtosecond laser
nanoprinting and projection 3D bioprinting to create 3D scaffolds using a variety
of biomaterials. These 3D biomaterials are functionalized with precise control
of microarchitecture, mechanical properties (e.g., stiffness and Poisson’s
ratio) and growth factors. Such functional biomaterials allow us to investigate
cell-microenvironment interactions at nano- and microscales in response to
integrated physical and chemical stimuli.
10:45 Synthetic Capillaries: Engineering Microscale Blood Flow
Gregory Timp, Ph.D., Keough-Hesburgh Professor of Engineering and Systems
Biology, Colleges of Science and Engineering, University of Notre Dame
Capillaries pervade human physiology. The lack of perfusion associated with
capillaries is especially problematic in thick engineered tissue because it
leads to hypoxic stress and necrosis. We show it is possible to create in vitro
a microenvironment that emulates a capillary using “live cell lithography” by
controlling the type and position of cells on a composite hydrogel scaffold.
These constructs support the forces and nutrient gradients associated with
blood flow.
11:15 A New 3D Model toTest Clonal Expansion andTreatment
Efficacy of Potential Drugs for Multiple Myeloma
Bhagavathi Narayanan, Ph.D., Associate Professor, Environmental Medicine,
NYU School of Medicine
Methacrylated hyaluronic acid-based 3D hybrid hydrogel provides a unique ex
vivo system that mimics a physiologically similar human microenvironment
suitable for examining the behavior of invasive cancer cells. Most important, 3D
hydrogel with differences in matrix composition and stiffness represents a new
version of 3D model that supports clonal expansion, migration, multiplication
and differentiation of cancer cells. Clonal expansion within encapsulated
hydrogels enables assessment of the treatment efficacy of potential drugs.
»»CLOSING KEYNOTE PRESENTATION
11:45 Scaling and Systems Biology for Integrating
Multiple Organs-on-a-Chip
John P. Wikswo, Ph.D., Founding Director, Vanderbilt Institute for
Integrative Biosystems Research and Education and Gordon A. Cain
University Professor, Biomedical Engineering, Vanderbilt University
Determination of the toxicity of drugs, consumer products and
industrial chemicals will benefit from quantitative systems approaches
to pharmacology and toxicology. By supporting heterogeneous
cell populations and complex 3D extracellular matrices, tissue-
engineered organs-on-chips and human organ constructs provide in
vitro organotypic culture models for tissue-scale toxicology that are
more realistic than static, planar, monolayer, immortal monocultures.
Properly coupled, they create a new class of in vitro microphysiological
systems models.
12:30 pm Close of Engineering Functional 3D Models and
Organotypic Culture Models forToxicology Conferences

10
While more informative than cell-free biochemical assays, monolayer or suspension cell culture HTS assays still fail to accurately reflect the
human cellular microenvironment. There is a need for physiologically-relevant cellular models for drug screening and functional analysis that
provide high predictive value for clinical efficacy and safety of compounds. The 3-dimensional cell culture models mimic the human tissue
microenvironment and provide more accurate information for compound and target selection, thereby reducing late-stage attrition. Cambridge
Healthtech Institute’s Second Annual Screening and Functional Analysis of 3D Models meeting will explore the use of 3D models to profile
compound action and predict toxicity and efficacy. The meeting will cover assay development using 3D cellular models, high-content analysis
and imaging of 3D models, and applications of screening 3D models for compound profiling and target discovery/validation.
Second Annual
Screening and Functional Analysis of 3D Models
Complex Cellular Models Predictive of Human Response to Improve Early Decision Making
PHENOTYPIC SCREENING OF 3D MODELS
Aron Jaffe, Ph.D., Novartis Institutes for BioMedical Research
1:35 Developing and Utilizing 3D Culture Systems for Novel
Target Discovery
Aron Jaffe, Ph.D., Senior Investigator, Developmental and Molecular
Pathways, Novartis Institutes for BioMedical Research
Target identification and validation have historically relied on immortalized or
tumor cell lines grown on plastic. Recent techniques involving growth of cells
in three-dimensional matrices have enabled modeling of cellular processes
in an environment that more closely resembles the in vivo setting. This
presentation will highlight the strategies for designing complex cellular assays
for target discovery using medium and high-throughput screening methods in
three dimensions.
2:00 3D versus 2D: Insight from Pharmacology and Genomics
Jean-Louis Klein, Ph.D., Principal Scientist, Target and Pathway Validation,
Platform Technology and Science, GlaxoSmithKline
Available)
TARGET SCREENING
Sponsored by
2:50 Showcase #2
3:10 Showcase #3
Dynamics, Inc.
4:30 Drug Discovery and Development of Novel Anticancer
Agents: Applications of Novel 3D MulticellularTumor Spheroid
Models
force in the most prominent human diseases. In particular, EMT driven tumor
Formation
in a high-content co-culture 3D spheroid screen. Subsequently we were
target tumors.
Models
Dynamics, Inc.
toxicity screening.
5:45 Close of Day

FASTCongress.com 11
or Morning Coffee
ENGINEERING COMPLEX 3D MODELS OF TUMOR
MICROENVIRONMENT FOR DRUG SCREENING AND
FUNCTIONAL ANALYSIS
Mary C. Farach-Carson, Ph.D., Rice University
8:10Targeted Electric FieldTherapy Development in 3D Models of
the Heterogeneous Glioma Microenvironment
Scott S. Verbridge, Ph.D., Assistant Professor, School of Biomedical
Engineering and Sciences, Virginia Tech – Wake Forest University
3D tissue models that incorporate the physico-chemo-cellular heterogeneities of
human tumors are a valuable tool for the development of treatments targeted
against the cells that resist traditional therapies. We will discuss our recent
work in targeting the physical properties of therapy resistant brain cancer
cells, leveraging 3D models to analyze the impact of cell type and mechanical
microenvironment on cellular response to high frequency electric fields.
8:35Targeting Physical and Stromal Determinants ofTumor
Heterogeneity in Bioengineered 3D Models
Imran Rizvi, Ph.D., Instructor, Medicine and Dermatology, Harvard Medical
School; Associate Bioengineer, Brigham and Women’s Hospital; Assistant,
Biomedical Engineering, Wellman Center for Photomedicine, Massachusetts
General Hospital
The biological characteristics and treatment response of cancers is influenced
by an array of factors including flow-induced shear stress, stromal partners, and
matrix composition, which play deterministic roles in the fate of disseminated
tumours. Research platforms that integrate these cues are critically needed to
identify mechanism-based combinations. Current findings will be presented
on the impact of flow and stromal partners, including tumor endothelial cells,
on the biological characteristics of 3D co-cultures, and their susceptibility to
conventional and emerging therapies.
9:00 3D Hydrogel Co-Culture Systems for Growing Patient-
Derived Xenografts: Use in Selective Drug Screening
Mary C. Farach-Carson, Ph.D., Ralph and Dorothy Looney Professor,
Biochemistry and Cell Biology; Scientific Director, BioScience Research
Collaborative, Rice University
Building on success culturing metastatic prostate cancer (PCa) cell lines
using 3D HA-based hydrogels, we now can culture ‘never in 2D’ patient-
derived xenograft (PDX) tumors alone or with other cells from the tumor
microenvironment. Hydrogel-encapsulated PDX tumoroids retain viability over
two weeks, proliferate and express androgen receptor, providing a valuable new
platform for drug discovery and screening. We now aim to eliminate the ‘middle
mouse’– a leap towards personalized medicine.
9:25 Human Stroma-Derived Extracellular Matrices: 3D ECM
Physiological Systems
Edna Cukierman, Ph.D., Associate Professor, Cancer Biology,
Fox Chase Cancer Center
The talk will describe desmoplasia (i.e., cancer-associated) and fibrosis in vivo-
like 3D ECM models. It will highlight the system’s physiologic and pathologic
relevance. The seminar will illustrate target validation, phenotype assessment,
functional analysis and drug efficacy uses. Assorted tumor-associated
microenvironments will showcase tissue patterning, multi-spectra acquisitions
and digital imaging analyses together with classic cell biology and biochemistry
approaches. Finally, the use of well-annotated human pathological samples will
establish clinical applicability.
ENGINEERING IN VITRO MODELS OF CANCER METASTASIS
Alan H. Wells, M.D., D.M.Sc., University of Pittsburgh
10:50 In vitro Models for Metastatic Disease
Roger D. Kamm, Ph.D., Cecil and Ida Green Distinguished Professor,
Biological and Mechanical Engineering, MIT
11:15 Monitoring Extravascular Migratory Metastasis of
Angiotropic Cancer Cells Using a 3D in vitro Co-Culture System
Claire Lugassy, M.D., Research Associate Professor, Pathology and Lab
Medicine, UCLA School of Medicine; Member, Jonsson Comprehensive
Cancer Center
During extravascular migratory metastasis (EVMM), angiotropic tumor
cells migrate along the abluminal vascular surfaces without intravasation
(pericytic-mimicry) and may spread to nearby or more distant sites. Our recent
publication in Nature confirmed again the importance of this underexplored
metastatic pathway. We have developed a fluorescence-based 3D co-culture
model to monitor in real time single tumor cell migration/EVMM in a vascular
microenvironment. This assay can be adapted for anticancer drug screening.
11:40 An All-Human Microphysiologic Liver System for
Carcinoma Metastasis
Alan H. Wells, M.D., D.M.Sc., Vice Chair and Thomas J. Gill III Professor,
Pathology, University of Pittsburgh
Metastases kill patients, but disseminated cancers are resistant to
therapies. The tumor biological events behind this are unknown due
to lack of relevant model systems. Further, humans metabolize agents
and present toxicities uniquely, hampering drug development. We have
developed an all-human microphysiological system of the liver to study
both tumor behavior in the common metastatic site, and drug metabolism/
efficacy in the main metabolizing organ.
12:05 Using Block Cell Printing to Develop Single Cell Arrays for
Drug Screening
Lidong Qin, Ph.D., Associate Member, Nanomedicine, Methodist Hospital
Research Institute; Assistant Professor, Cell and Developmental Biology, Weill
Cornell Medical College
12:30 pm Close of Screening and Functional Analysis of 3D
Models Conference
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12
It is recognized that in vitro toxicology studies are complex. Organotypic culture models (OCMs)—tissue models that mimic in vivo
tissue architecture through interactions of heterotypic cell types and extracellular matrices—are increasingly being explored for
prediction of organ-specific toxicity. As these models become more widely used for chemical and drug toxicity testing, there is a
corresponding need to establish standardized testing conditions, endpoint analyses and acceptance criteria. Cambridge Healthtech
Institute’s Inaugural Organotypic Culture Models forToxicology meeting addresses the balanced approach between sample
throughput and biological relevance, providing better in vitro tools to replace animal testing and predict human risk assessment.
Inaugural
Organotypic Culture Models for Toxicology
In vitro Screening Tools for Modeling and Predicting Organ-Specific Toxicity
SUNDAY, NOVEMBER 16
Registration
6:00-9:00 (SC2) Exploring 3D Printing, Bioinks and Scaffolds
MONDAY, NOVEMBER 17
8:15 Welcome and Chairperson’s Opening Remarks (Sponsorship
Opportunity Available)
»»KICKOFF KEYNOTE PRESENTATION
8:25 Personalized Reading and Writing of Organs
George Church, Ph.D., Professor, Genetics, Harvard Medical
School; Professor, Health Sciences and Technology, Harvard and
MIT; Founding Core Faculty Member, Platform Lead, Synthetic
Biology, Wyss Institute for Biologically Inspired Engineering, Harvard
University
We need better systems for testing small molecule, protein and
nucleic acid therapeutics—ideally personalized organs, as can be
achieved via iPSC, ePSC or SCNT-ESCs. One or more variants of
unknown significance can be tested for a causal role by using CRISPR
genome editing and a variety of simple cell types and complex organs
and systems derived by epigenomic reprogramming. This engineering
system is especially useful in leveraging the world’s only open-access
(with very well-characterized -omic and medical data) human subjects
(personalgenomes.org). The faithfulness of the organ system models,
as well as their drug responses, can be checked using fluorescent in
situ sequencing (FISSEQ).
KIDNEY – NEPHROTOXICITY TESTING STRATEGIES
9:05 A Human Kidney Microphysiological System
Jonathan Himmelfarb, M.D., Director, Kidney Research Institute; Joseph W.
Eschbach Endowed Chair in Kidney Research; Professor, Medicine, Division of
Nephrology, University of Washington
We have designed, implemented and tested a tissue-engineered human
kidney microphysiological system. The system is developed to fully evaluate
uptake, metabolism and elimination of xenobiotics in a human tissue-derived,
in vitro 3-dimensional system that accurately reflects human physiology.
The microphysiological system can be used to predict disposition kinetics
of xenobiotics and also assess the response to kidney injury inflicted by
endogenous and exogenous toxicants.
9:35 Mini-Kidneys Derived from Human Stem Cells
Juan Carlos Izpisua Belmonte, Ph.D., Roger Guillemin Chair and Professor,
Gene Expression Laboratories, Salk Institute for Biological Sciences
Human pluripotent stem cells hold great promise for the modeling of disease
and toxicology studies upon directed differentiation. The kidney represents
an architecturally complex organ responsible for blood toxin clearance. Here
we discuss how derivation of functional renal structures in vitro can open
unprecedented opportunities for the modeling of kidney disease and general
toxicology studies.
HEART – CARDIOTOXICITY TESTING METHODS
10:30 Engineering Macroscale 3D Human CardiacTissue from
hPSCs
Kareen Coulombe, Ph.D., Assistant Professor, Engineering, School of
Engineering, Brown University
Regenerating the heart post-injury requires a large, muscular implant
contributing contractile force to aid the heart’s pumping action. We are
developing 3D engineered tissues of various geometries using cardiomyocytes
derived from human pluripotent stem cells to study tissue architecture, cellular
phenotype, passive and active mechanical properties and regeneration in a rat
model of myocardial infarction. We focus on vascularization and contractility
in vivo and design tissues in vitro for translational applications, including
toxicology testing.
11:00 Screening Drug-Induced Arrhythmia Events Using Human-
Induced Pluripotent Stem Cell-Derived Cardiomyocytes
Andrew S. Lee, Ph.D., Co-Founder and CSO, Stem Cell Theranostics
Cardiotoxicity is a leading cause of drug attrition during pharmaceutical
development and of market withdrawal due to safety concerns. Recent
advances in induced pluripotent stem cell (iPSC) technology have allowed
the generation of cardiomyocytes that can be used to model drug-induced
cardiotoxicity. We describe a novel iPSC platform that utilizes patient-specific
cardiomyocytes for personalized prediction of cardiac drug toxicity in patient
subpopulations with a history of cardiovascular disease.
11:30 Micro- and Nanotechnologies for 3D CardiacTissue
Constructs with Functionalized Nanoparticles
Su-Ryon Shin, Ph.D., Instructor, Medicine, Harvard Medical School
The development of highly organized and functional 3D complex constructs in
vitro is important in tissue engineering. In particular, heart muscles are dense
quasi-lamellar and highly vascularized tissues in which functional syncytia of the
cardiomyocytes are tightly interconnected with gap junctions. To address these
challenges, we are developing a novel approach that combines nanoparticles
and microfabrication techniques to create dense and highly organized 3D cardiac
tissue constructs with biomimetic electrophysiological function.
12:00 pm Close of Session
12:15 Luncheon Presentation (Sponsorship Opportunity Available)
or Enjoy Lunch onYour Own

FASTCongress.com 13
HIGH-DIMENSIONAL TISSUE AND ORGAN MODELS:
ADVANTAGES AND DISADVANTAGES OF 2D VS. 3D
Rosemarie Hunziker, Ph.D., Director, Tissue Engineering and Regenerative
Medicine, National Institute of Biomedical Imaging and Bioengineering,
1:35 OrganotypicThree-DimensionalTissue Models
Heike Walles, Ph.D., Chair and Head, Regenerative Therapies, Tissue
Engineering and Regenerative Medicine and Fraunhofer IGB Project Group,
University Hospital Würzburg
Our group has been committed to the development of alternative human test
systems that reflect the body’s complex characteristics. We have succeeded
in building up skin equivalents that can be extended by other cells. Moreover,
we have established a trachea and an intestine tissue model as different tumor
model systems. To ensure culture conditions that are similar to the cells’ natural
environment in the body, specific bioreactor systems have been developed.
2:05 Customized 3D Cell Cultures and
Assays Showcase (Sponsorship Opportunities Available)
All agree that 3D cell models that are morphologically and
functionally similar to native tissue hold the potential to improve in
vitro cell-based assays. However, it is important to note that there
is no one-size-fits-all solution; each cell type requires a different
environment and different assays to screen them. This session
showcases companies that are driving cell culture and screening
assays into the new dimension of studying health vs. disease and
drug response.
2:05 Showcase #1
2:25 Showcase #2
2:45 Showcase #3
3:45 Organs-on-Chips to Screen for Drug Efficacy and
Toxicity
Kristin Fabre, Ph.D., Scientific Program Manager, NCATS, National
The Microphysiological Systems Program, comprised of an MPS
Consortium of academic and government entities, aims to bioengineer
platforms (or chips) that mimic human organ systems. These platforms
help predict efficacy and toxicity of candidate compounds faster,
cheaper and with fewer animal models than current methods. The
project’s goal is to incorporate human iPSC-derived cell sources
(inducible pluripotent stem cells) into corresponding organ modules
and create an integrated Human-on-a-Chip to study drug response
within human bodies.
4:30 Organs-on-Chips: Highly Functional
Microphysiological Systems to Predict Human Physiology
and Pathobiology
Geraldine A. Hamilton, Ph.D., Senior Staff Scientist, Wyss Institute
for Biologically Inspired Engineering, Harvard University
This presentation focuses on our novel biomimetic microsystem
technologies and their potential application in predicting efficacy,
safety and mechanism of action for new drugs, chemicals and
cosmetics. Human organs-on-chips provide exciting new approaches
to attack fundamental questions in biology and develop smart
in vitro surrogates. This technology also offers a more human-
relevant alternative to current animal-based approaches for disease
model development.
6:30-9:30 (SC4) Engineering Microfluidic Cell Culture Chips
or Morning Coffee
LIVER AND GUT – HEPATOTOXICITY AND
GASTROINTESTINAL TOXICITY TESTING REGIMES
James J. Hickman, Ph.D., University of Central Florida
8:35 iPSC-Derived Hepatic Model Systems for Investigating
Mechanisms of IDILI
Jingtao Lu, Ph.D., Research Scientist, The Hamner Institutes for Health
Sciences
Induced pluripotent stem cell-derived hepatocytes (iHC) were assessed as
a drug-induced liver injury model. iHCs were comparable to primary human
hepatocytes (pHH) in architecture, gene expression profiles, CYP activities
and sensitivities to multiple model hepatotoxins. In the study of isoniazid
(INH)-induced idiosyncratic liver injury (IDILI), iHCs showed pHH-like sensitivity
towards INH-mediated cytotoxicity, protein adduction and mitochondrial
toxicity. Combined results support iHCs as a promising new hepatic model to
investigate IDILI mechanisms.
9:05 Biomimiks as Chemosynthetic Livers
Mukund S. Chorghade, Ph.D., CSO, Empiriko Corporation
Our proprietary technology mimics metabolism of chemical entities for
pharmaceuticals, enables prediction of metabolism patterns and introduces
new paradigms for drug discovery and drug-drug interactions. Our catalysts
provide speed, stability and scalability. We predict structures of metabolites,
prepare them on scale and elucidate chemical structures. Comprehensive safety
evaluation enables complete metabolism studies, confirmation of structure
and quantitative measures of toxicity. This is an animal-free platform for
safety-relevant metabolites.
9:35Three-Dimensional Human Small Intestine Models for
ADME-Tox Studies
Jiajie Yu, Ph.D., Research Scientist, Linda Griffith Laboratory, Biological
Engineering, Massachusetts Institute of Technology
In vitro cell-based human small intestine models have been widely used in
drug preclinical development. However, these traditional models could provide
misleading results due to their relatively poor recapitulation of small intestine
physiology. This presentation focuses on recent breakthroughs of developing
more physiological in vitro human small intestine models as well as their
impacts on preclinical ADME-Tox studies.
11:15 Body-on-a-Chip Systems forToxicological Evaluations
James J. Hickman, Ph.D., Professor, NanoScience Technology, Chemistry,
Biomolecular Science and Electrical Engineering, University of Central Florida
Replacing animals in toxicology and drug discovery with integrated functional
organ constructs in a serum-free defined system composed of human cells
will greatly reduce the cost and increase the relevance of these studies.
Furthermore, utilizing functional human models in both 2D and 3D systems
will facilitate both acute and chronic compound evaluations for toxicological
applications that are not currently possible in vitro.
»»CLOSING KEYNOTE PRESENTATION
11:45 Scaling and Systems Biology for Integrating
Multiple Organs-on-a-Chip
John P. Wikswo, Ph.D., Founding Director, Vanderbilt Institute for
Integrative Biosystems Research and Education and Gordon A. Cain
University Professor, Biomedical Engineering, Vanderbilt University
Determination of the toxicity of drugs, consumer products and
industrial chemicals will benefit from quantitative systems approaches
to pharmacology and toxicology. By supporting heterogeneous
cell populations and complex 3D extracellular matrices, tissue-
engineered organs-on-chips and human organ constructs provide in
vitro organotypic culture models for tissue-scale toxicology that are
more realistic than static, planar, monolayer, immortal monocultures.
Properly coupled, they create a new class of in vitro microphysiological
systems models.
12:30 pm Close of Engineering Functional 3D Models and
Organotypic Culture Models forToxicology Conferences

14
Traditional drug screening relies on monolayer cell culture, which is not always predictive of natural physiological state. This is especially
problematic in cancer drug discovery, where simple cell cultures are not predictive of complex tumor microenvironment that consists
of various cell types that interact in 3-dimensional structures. As the cost of drug development rises, there is increasing pressure for
more predictive in vitro models for functional analysis and compound characterization. Cambridge Healthtech Institute’s Second Annual
Physiologically-Relevant CellularTumor Models for Drug Discovery meeting will focus on the latest advances in 3D cellular tumor
models and complex co-culture systems for functional analysis studies and compound screening/characterization.
Second Annual
Physiologically-Relevant Cellular
Tumor Models for Drug Discovery
In vitro Models of Tumor Microenvironment for New Cancer Target
and Drug Discovery
ENGINEERING AND SCREENING TUMOR SPHEROID
MODELS
Mitchell Ho, Ph.D., National Cancer Institute
1:35 NewTricks for Spheroids: Mimicking Stromal Interactions,
Investigating Nanoparticle Drug Delivery, and Modeling
Resection
Mark Grinstaff, Ph.D., Professor, Chemistry, Boston University
2:00 Functional Analysis ofTherapeutic Antibodies and Antigens
Using ex vivoTumor Spheroids
Mitchell Ho, Ph.D., Chief, Antibody Therapy Section, Laboratory of Molecular
Biology, National Cancer Institute, National Institutes of Health
Tumor microenvironments present significant barriers to antibody therapy. We
established ex vivo tumor spheroids to study molecular mechanisms of antibody
drug resistance. The tumor spheroids may prove invaluable for identifying
potential targets in addition to providing an innovative platform for analyzing
therapeutic antibodies. We compared the global gene expression profiles of
spheroids and monolayers and identified genes specific to the 3-D biological
structure of mesothelioma. An update on generation of human single-domain
antibodies for cancer therapy will also be discussed.
Available)
TARGET SCREENING
Sponsored by
2:50 Showcase #2
3:10 Showcase #3
Dynamics, Inc.
4:30 Drug Discovery and Development of NovelAnticancer
Agents:Applications of Novel 3D MulticellularTumor Spheroid
Models
force in the most prominent human diseases. In particular, EMT driven tumor
Formation
in a high content co-culture 3D spheroid screen. Subsequently we were
target tumors.
Models
Dynamics, Inc.
toxicity screening.
5:45 Close of Day

FASTCongress.com 15
Hotel & Travel Information
Conference Hotel:
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Why Stay at the Hyatt Boston Harbor Hotel
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or Morning Coffee
ENGINEERING COMPLEX 3D MODELS OF TUMOR
MICROENVIRONMENT FOR DRUG SCREENING AND
FUNCTIONAL ANALYSIS
Mary C. Farach-Carson, Ph.D., Rice University
8:10Targeted Electric FieldTherapy Development in 3D Models of
the Heterogeneous Glioma Microenvironment
Scott S. Verbridge, Ph.D., Assistant Professor, School of Biomedical
Engineering and Sciences, Virginia Tech – Wake Forest University
3D tissue models that incorporate the physico-chemo-cellular heterogeneities of
human tumors are a valuable tool for the development of treatments targeted
against the cells that resist traditional therapies. We will discuss our recent
work in targeting the physical properties of therapy-resistant brain cancer
cells, leveraging 3D models to analyze the impact of cell type and mechanical
microenvironment on cellular response to high frequency electric fields.
8:35Targeting Physical and Stromal Determinants ofTumor
Heterogeneity in Bioengineered 3D Models
Imran Rizvi, Ph.D., Instructor, Medicine and Dermatology, Harvard Medical
School; Associate Bioengineer, Brigham and Women’s Hospital; Assistant,
Biomedical Engineering, Wellman Center for Photomedicine, Massachusetts
General Hospital
The biological characteristics and treatment response of cancers is influenced
by an array of factors including flow-induced shear stress, stromal partners, and
matrix composition, which play deterministic roles in the fate of disseminated
tumours. Research platforms that integrate these cues are critically needed to
identify mechanism-based combinations. Current findings will be presented
on the impact of flow and stromal partners, including tumor endothelial cells,
on the biological characteristics of 3D co-cultures, and their susceptibility to
conventional and emerging therapies.
9:00 3D Hydrogel Co-Culture Systems for Growing Patient-
Derived Xenografts: Use in Selective Drug Screening
Mary C. Farach-Carson, Ph.D., Ralph and Dorothy Looney Professor,
Biochemistry and Cell Biology; Scientific Director, BioScience Research
Collaborative, Rice University
Building on success culturing metastatic prostate cancer (PCa) cell lines
using 3D HA-based hydrogels, we now can culture ‘never in 2D’ patient-
derived xenograft (PDX) tumors alone or with other cells from the tumor
microenvironment. Hydrogel-encapsulated PDX tumoroids retain viability over
two weeks, proliferate and express androgen receptor, providing a valuable new
platform for drug discovery and screening. We now aim to eliminate the ‘middle
mouse’– a leap towards personalized medicine.
9:25 Human Stroma-Derived Extracellular Matrices: 3D ECM
Physiological Systems
Edna Cukierman, Ph.D., Associate Professor, Cancer Biology,
Fox Chase Cancer Center
The talk will describe desmoplasia (i.e., cancer-associated) and fibrosis in vivo-
like 3D ECM models. It will highlight the system’s physiologic and pathologic
relevance. The seminar will illustrate target validation, phenotype assessment,
functional analysis and drug efficacy uses. Assorted tumor-associated
microenvironments will showcase tissue patterning, multi-spectra acquisitions
and digital imaging analyses together with classic cell biology and biochemistry
approaches. Finally, the use of well-annotated human pathological samples will
establish clinical applicability.
ENGINEERING IN VITRO MODELS OF CANCER METASTASIS
Alan H. Wells, M.D., D.M.Sc., University of Pittsburgh
10:50 In vitro Models for Metastatic Disease
Roger D. Kamm, Ph.D., Cecil and Ida Green Distinguished Professor,
Biological and Mechanical Engineering, MIT
11:15 Monitoring Extravascular Migratory Metastasis of
Angiotropic Cancer Cells Using a 3D in vitro Co-Culture System
Claire Lugassy, M.D., Research Associate Professor, Pathology and Lab
Medicine, UCLA School of Medicine; Member, Jonsson Comprehensive
Cancer Center
During extravascular migratory metastasis (EVMM), angiotropic tumor
cells migrate along the abluminal vascular surfaces without intravasation
(pericytic-mimicry) and may spread to nearby or more distant sites. Our recent
publication in Nature confirmed again the importance of this underexplored
metastatic pathway. We have developed a fluorescence-based 3D co-culture
model to monitor in real time single tumor cell migration/EVMM in a vascular
microenvironment. This assay can be adapted for anticancer drug screening.
11:40 An All-Human Microphysiologic Liver System for
Carcinoma Metastasis
Alan H. Wells, M.D., D.M.Sc., Vice Chair and Thomas J. Gill III Professor,
Pathology, University of Pittsburgh
Metastases kill patients, but disseminated cancers are resistant to
therapies. The tumor biological events behind this are unknown due
to lack of relevant model systems. Further, humans metabolize agents
and present toxicities uniquely, hampering drug development. We
have developed an all-human microphysiological system of the liver to
study both tumor behavior in the common metastatic site, and drug
metabolism/efficacy in the main metabolizing organ.
12:05 Using Block Cell Printing to Develop Single Cell Arrays for
Drug Screening
Lidong Qin, Ph.D., Associate Member, Nanomedicine, Methodist Hospital
Research Institute; Assistant Professor, Cell and Developmental Biology, Weill
Cornell Medical College
12:30 pm Close of Physiologically-Relevant CellularTumor
Models Conference

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Pricing and Registration Information
NOVEMBER 17-18 NOVEMBER 18-19
Phenotypic Drug Discovery - Part I Phenotypic Drug Discovery - Part II
Engineering Functional 3D Models Screening and Functional Analysis of 3D Models
Organotypic Culture Models for Toxicology Physiologically-Relevant Cellular Tumor Models
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Sunday Evening, November 16
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(SC1) Introduction to High-Content
Phenotypic Screening
(SC3) Stem Cell Models for Drug Discovery (SC5) Expert ThinkTank: How to Meet the
Need for Physiologically-Relevant Assays?
(SC2) Exploring 3D Printing, Bioinks
and Scaffolds
(SC4) Engineering Microfluidic Cell
Culture Chips
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