CongressRegister by August 2 and save up to $400!Organized by:Cambridge Healthtech Institute FASTCONGRESS.comOctober28-30,...
FASTCONGRESS.com2With the tremendous expense of bringingnew drugs to market, a focus on improvingthe outcome of first-stag...
3Functional Analysis & Screening Technologies CongressCHI offers comprehensive sponsorship packages which include presenta...
FASTCONGRESS.com4Monday, October 287:30 am Main Conference Registration and Morning CoffeeEngineering 3-D Systems8:15 Chai...
Functional Analysis & Screening Technologies Congress 51:35 3-D IntestinalTissue ModelsJohn March, Ph.D., Associate Profes...
FASTCONGRESS.com6October28-29 Phenotypic Drug DiscoveryPhenotypic Drug DiscoveryMaximizing Information in Early Drug Disco...
Phenotypic Drug DiscoveryFunctional Analysis & Screening Technologies Congress 72:25 Human Induced Pluripotent Stem Cells ...
FASTCONGRESS.com8Screening and FunctionalAnalysis of 3-D ModelsOctober29-30 Screening and FunctionalAnalysis of 3-D Models...
Functional Analysis & Screening Technologies Congress 96:00-9:00 Dinner ExpertThinkTank* (see page 2 for details)SC4: How ...
FASTCONGRESS.com10Physiologically-Relevant CellularTumor Models for Drug DiscoveryOctober29-30Physiologically-Relevant Cel...
11Functional Analysis & Screening Technologies Congress6:00-9:00 Dinner ExpertThinkTank* (see page 2 for details)SC4: How ...
Additional registration detailsEach registration includes all conferencesessions, posters and exhibits, foodfunctions, and...
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FAST: Functional Analysis & Screening Technologies Congress

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With the tremendous expense of bringing new drugs to market, a focus on improving the outcome of first-stage research is critical. Recent evidence confirms the need for innovative screening systems utilizing assay design on three-dimensional tissue models and phenotypic models. This functional analysis will allow for more accurate biological response. Cambridge Healthtech Institute is pleased to introduce FAST: Functional Analysis & Screening Technologies Congress to bring together drug research and development teams for practical discussion, solutions and case studies for refining these first-stage drug discovery methods.

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FAST: Functional Analysis & Screening Technologies Congress

  1. 1. CongressRegister by August 2 and save up to $400!Organized by:Cambridge Healthtech Institute FASTCONGRESS.comOctober28-30,2013• LeMéridienCambridge-MIT• Cambridge,MAEngineering Functional3-DTissue ModelsScreening and FunctionalAnalysis of 3-D ModelsPhenotypic Drug DiscoveryPhysiologically-Relevant CellularTumor Models for Drug DiscoveryOctober28-29October29-30Functional AnalysisScreening Technologies&Corporate Sponsors
  2. 2. FASTCONGRESS.com2With the tremendous expense of bringingnew drugs to market, a focus on improvingthe outcome of first-stage research is critical.Recent evidence confirms the need forinnovative screening systems utilizing assaydesign on three-dimensional tissue modelsand phenotypic models. This functionalanalysis will allow for more accurate biologicalresponse. Cambridge Healthtech Institute ispleased to introduce FAST: Functional Analysis& Screening Technologies Congress to bringtogether drug research and developmentteams for practical discussion, solutions andcase studies for refining these first-stage drugdiscovery methods.SHORT COURSES*Sunday evening, October 27, 6:00-9:00 PMSC1 Pre-Conference Dinner Short CourseScaffolds: Bridging the Gap between 2-D and 3-DThree-dimensional (3-D) in vitro models aim to bridge the gap betweenstandard two-dimensional (2-D) cell-based assays and the in vivo environment.Scaffolds provide the foundation for this dimensional shift. Well-designedscaffolds provide the necessary local structural, mechanical and environmentalcues to direct functional growth. Additionally, scaffolds help preserve thebioactivities of the biomolecules helping control biomolecule distribution andrelease. This interactive short course is designed to provide practical solutionsfor moving from 2-D to 3-D. Build your scaffold expertise!Instructors:EmergingTechnologies for Assembly of Microscale HydrogelsUtkan Demirci, Ph.D., Assistant Professor, Medicine and Health Sciences andTechnology, Brigham and Women’s Hospital, Harvard Medical SchoolUse of 3-D Porous Natural Polymer Scaffolds for in vitroTumorMicroenvironment ModelsStephen J. Florczyk, Ph.D., Biomedical Engineer, Biomaterials Group,Biosystems and Biomaterials Division, National Institute of Standards andTechnologyMerging MicroscaleTechnologies and Advanced Biomaterials forCardiovascularTissue EngineeringNasim Annabi, Ph.D., Research Scientist, Ali Khademhosseini Laboratory,Tissue Engineering, Harvard Medical SchoolMonday evening, October 28, 6:00-9:00 PMSC2 Dinner Short CourseAutomating a 3-D Culture Screening Laboratory:Meeting the ChallengesThe paradigm shift from 2-D to 3-D cell culture models is under way andprogressing rapidly. Although the screening community recognizes thefunctionality that 3-D models can provide, their implementation in any high-throughput screening laboratory is hampered by the lack of appropriateautomation tools and technologies. In addition, when using complex models,their costs and read-out speed have to be taken into account. This interactiveshort course provides insights on advancing the laboratory science andtechnology to move drug discovery into a new 3-D dimension.Instructors to be AnnouncedMonday evening, October 28, 6:00-9:00 PMSC3 Dinner Short CourseIntroduction to High-Content Phenotypic ScreeningThe ever-increasing demand for improved productivity in research through thegeneration of robust analysis outputs has driven both the development anddeployment of automated high-content analysis (HCA) and phenotypic cell-based approaches to drug discovery. In contrast to the more traditional cellularanalysis and target-based approaches, here the researcher is able evaluatethe efficacy of potential therapeutics by monitoring the physiological state ofcells through the simultaneous analysis of multiple cellular parameters in thecontext of an intact biological system. This course will cover the key features ofHCS/A technologies and the best approaches to using these technologies forphenotypic cell-based screening.Instructor: Anthony M. Davies, Ph.D., Director, Irish National Center forHigh-Content Screening and Analysis (INCHA)Tuesday evening, October 29, 6:00-9:00 PMSC4 Dinner Expert ThinkTankHow to Meet the Need for Physiologically-RelevantAssays?Moderator: Lisa Minor, Ph.D., President, In Vitro Strategies, LLCPanelists:Anne Bang, Ph.D., Director, Cell Biology, Sanford-Burnham Medical ResearchInstituteAnthony M. Davies, Ph.D., Director, Irish National Center for High-ContentScreening and Analysis (INCHA)Marina Fitzek, Associate Principal Scientist, Discovery Sciences, AstraZenecaAaron Morris, Ph.D., Lab Head, Cancer Biology, Sanofi OncologyMichelle Palmer, Ph.D., Director, Discovery and Preclinical Research, BroadInstituteCaroline Shamu, Ph.D., Lecturer, Systems Biology and Director, ICCB-Longwood, Harvard Medical SchoolD. Lansing Taylor, Ph.D., Director, University of Pittsburgh Drug DiscoveryInstitute and Allegheny Foundation; Professor, Computational and SystemsBiology, University of PittsburghFor a detailed description of the ExpertThinkTank please visitwww.FASTCongress.com.FEATURED SPEAKERSKaren J.L. Burg, Ph.D.Hunter Endowed Chair and Professor of Bioengineering, Clemson UniversityD. Lansing Taylor, Ph.D.Director, University of Pittsburgh Drug Discovery InstituteSteve Ludbrook, Ph.D.Section Head, Screening and Compound Profiling, GlaxoSmithKlineAaron Morris, Ph.D.Lab Head, Cancer Biology, Sanofi Oncology*A separate registration is required to attend a short course.
  3. 3. 3Functional Analysis & Screening Technologies CongressCHI offers comprehensive sponsorship packages which include presentationopportunities, exhibit space and branding, as well as the use of the pre and post-show delegate lists. Customizable sponsorship packages allow you to achieve yourobjectives before, during, and long after the event. Signing on early will allow you tomaximize exposure to qualified decision-makers!Agenda PresentationsShowcase your solutions to a guaranteed, highly-targeted audience. Packageincludes a 15 or 30-minute podium presentation within the scientific agenda, exhibitspace, on-site branding and access to cooperative marketing efforts by CHI.Breakfast & Luncheon PresentationsOpportunity includes a 30-minute podium presentation. Boxed lunches aredelivered into the main session room, which guarantees audience attendance andparticipation. A limited number of presentations are available for sponsorship andthey will sell out quickly. Sign on early to secure your talk!Invitation-Only VIP Dinner/Hospitality SuiteSponsors will select their top prospects from the conference pre-registration list for anevening of networking at the hotel or at a choice local venue. CHI will extend invitationsand deliver prospects. Evening will be customized according to sponsor’s objectives i.e.:• Purely social• Focus group• Reception style• Plated dinner with specificconversation focusExhibitExhibitors will enjoy facilitated networking opportunities with high-level conferencedelegates. Speak face-to-face with prospective clients and showcase your latestproduct, service, or solution.*Inquire about additional branding opportunities!Looking for additional ways to drive leads to your sales team?CHI can help!We offer clients numerous options for custom lead generation programs to addresstheir marketing and sales needs, including:• Web Symposia• Whitepapers• Market Surveys • Podcasts• And More!To customize your participation at this event, please contact:Ilana Quigley – Business Development Manager781-972-5457 | iquigley@healthtech.comSponsorship,Exhibit,andLead Generation OpportunitiesFlight discounts and car rental discounts areavailable.Visit our website for more details.Hotel &Travel InformationConference Venue and Hotel:Le Méridien Cambridge-MIT20 Sidney StreetCambridge, MA 02139Phone: 617-577-0200Discounted Room Rate: $249 s/dDiscounted Cut-off Date: October 7, 2013Please visit our conference website or callthe hotel directly to reserve your sleepingaccommodations. Identify yourself as aCambridge Healthtech Institute conferenceattendee to receive the discounted room rate.Reservations made after the cut-off date orafter the group room block has been filled(whichever comes first) will be accepted on aspace-andrate-availability basis. Rooms arelimited, so please book early.Why Stay at Le Méridien Cambridge–MIT?Le Méridien Cambridge-MIT, recipientof the 2013 TripAdvisor Certificate ofExcellence award, is an easy taxi ridefrom Logan Airport and boasts a primelocation – midway between historic Bostonand Harvard Square, both just a shorttrain ride away. Elegant guest rooms offercomplimentary wireless Internet to allconference attendees. Restaurants andthe MIT Museum are both just steps fromthe hotel. You’ll appreciate being close toall Boston has to offer – museums, history,shopping, the arts, and the home of the RedSox, Fenway Park!Media PartnersMedia Sponsors: Lead Sponsoring Publications:Web Partners:Sponsoring Publications:Sponsoring Organizations:
  4. 4. FASTCONGRESS.com4Monday, October 287:30 am Main Conference Registration and Morning CoffeeEngineering 3-D Systems8:15 Chairperson’s Opening Remarks»»Keynote PresentationS8:25TalkTitle to be AnnouncedLinda Griffith, Ph.D., Professor, Biological and Mechanical Engineering,Massachusetts Institute of Technology9:05 Designing aTunable 3-D Heterocellular Breast CancerTissueTest SystemKaren J.L. Burg, Ph.D., Hunter Endowed Chair and Professor ofBioengineering, Director, Institute for Biological Interfaces of Engineering,Clemson UniversityThe viability of a tissue-engineered product relies on cell-biomaterialinteraction and the design of an appropriate 3-D microenvironment.This presentation will highlight examples showing the importance ofmicroenvironment in influencing cellular behavior and will describe howone can purposefully tune this cell-material “handshake.” The potential ofspecialized 3-D cellular systems in personalized medicine will be discussed.9:45Tissue Engineering in Magnetic Levitation 3-DimensionalCulture SystemMikhail Kolonin, Ph.D., Associate Professor, John S. Dunn Research Scholar,Jerold B. Katz Distinguished Professor in Stem Cell Research,The BrownFoundation Institute of Molecular Medicine Center for Stem Cell andRegenerative Medicine, University ofTexas Health Science Center at HoustonWe present an application of 3-D levitation tissue culture system based onmagnetic nanoparticles to modeling white adipose tissue. We demonstrateefficient differentiation of mesenchymal progenitors into adipocytes achievedin parallel with endothelial cells organizing into vessel-like structures in 3-Dorganoids termed “adipospheres.” This magnetic levitation approach, enablingthe retention and self-organization of cell types composing a tissue in vivo,may provide advantages for quick and simple simulation of organs, cells ofwhich are difficult to maintain in conventional culture systems.10:15 Coffee Breakorgan short session: Lung Model applications10:30 An Engineered Model of the Airways with All PrimaryHuman CellsSonia Grego, Ph.D., Senior Scientist, Center for Materials and ElectronicTechnologies, RTI InternationalMicrofluidic systems enable biomimetic cell cultures for more physiologically-relevant models of human organs such as the lung. The lung is a primarysite of exposure to environmental insults and pathogens as well as anattractive drug delivery route. Microfluidic lung models often use immortalcell lines, which are conveniently maintained in culture but lack many of themorphological and functional characteristics of the original tissue. We havedeveloped a biomimetic multicellular 3-D model of the human conductingairways including all primary lung cells. Primary cells are recognized as theclosest in vitro representation of the tissue physiology. Our engineeredcellular construct enables novel studies of therapeutics and viral infections.11:00 Development of EngineeredTrachea-Lung Constructs:The New Respiratory Models to Study Lung Development,Physiology, Pathology orToxicologyJoan Nichols, Ph.D., Professor, Internal Medicine, Division of InfectiousDiseases, University of Texas Medical BranchTraditional cell culture assays to examine toxicity or pathogenicity in 2-Dsystems are flawed due to: 1) dependency on immortalized cell lines whichdo not adequately reflect biology and response of primary human cells, 2)reliance on single-cell systems that fail to recognize cell-cell interactions withthe microenvironment and 3) reliance on artificial 2-dimensional monolayersfor modeling complex diseases. Development of good in vitro human tissuemodels would help to bridge the gap in our current knowledge of lungresponses, as well as provide a better understanding of lung development,physiology and pathology. A benefit of our current in vitro lung model is thathypotheses generated from review of data from human disease studies canbe tested directly in engineered human tissue models. We are currently usingcomplex 3-D models to examine cell-based responses, physiologic functions,pathologic changes related to development of lung disease and lung fibrosis.11:30 Next-Generation Bioengineered 3-D HumanTissue-Equivalent Platform System to Validate High-Volume VaccineProductionThomas J. Goodwin, Ph.D., Disease Modeling and Tissue AnaloguesLaboratory, NASAAn advanced 3-D regenerative tissue-equivalent disease modeling anddetection system for most major human organs has been developed using aNASA platform. Normal human cells, tissue-engineered to grow in bioreactorssimulating aspects of microgravity, serve as a platform to identify progenitorcell and organoid cellular interactions, modulations in gene expression andcellular differentiation. This technology validates longitudinal DNA and RNAviral proliferation, genomics and host proteomic inflammatory responses. Thehuman lung epithelial cell construct mimics human respiratory epitheliumincluding polarization, tight junctions, desmosomes, microvilli, functionaltissue markers and maintains a long-term viral infective state without loss ofcellular function. This model is a paradigm shift for high-volume production ofvirus for vaccine production.12:00 pm Luncheon Presentation(Sponsorship Opportunity Available)or Lunch onYour Own3-D Model Systemsto ComprehendHealth vs. Disease States1:30 Chairperson’s Opening RemarksEngineering Functional 3-DTissue ModelsOctober28-29 Engineering Functional 3-DTissue ModelsNew Dimensions in Drug Discovery and DevelopmentSecond AnnualCompared to traditional cell-based assay monolayers, three-dimensional (3-D) models more closely mimic native tissues. 3-D tissue modelsprovide a means for systematic, repetitive and quantitative investigation of drugs, serving as platforms for screening of drugs as well aspharmacokinetic and pharmacodynamic analysis of drugs. That said, creating the more biologically relevant third dimension of tissue modelsrequires a multidisciplinary approach and multidisciplinary expertise. Cambridge Healthtech Institute’s Second Annual Engineering Functional3-DTissue Models meeting weaves together engineers, biologists and pharmacologists. As with any model, each specialty provides insightsinto the complete system advancing drug discovery and development, from designing the bioreactors, to engineering the 3-D models, tostudying healthy versus diseased states, to utilizing drug screening assays.
  5. 5. Functional Analysis & Screening Technologies Congress 51:35 3-D IntestinalTissue ModelsJohn March, Ph.D., Associate Professor, Biological and EnvironmentalEngineering, Cornell University2:05 Speaker to be Announced2:35 From iPSC to 3-D Skin Equivalents: Dynamic Platforms toStudy Human DiseaseJonathan Garlick, DDS, Ph.D., Professor, Oral Pathology, Sackler School ofGraduate Biomedical Sciences, Tufts University3:05 Refreshment Break in the Exhibit Hall with Poster ViewingCustomized 3-D Cell Cultures and Assays ShowcaseAll agree that 3-D cell models that are morphologically and functionallysimilar to native tissue hold the potential to improve in vitro cell-basedassays. However, it is important to note that there is no one-size-fits-allsolution; each cell type requires a different environment and differentassays to screen them. This session showcases companies that aredriving cell culture and screening assays into the new dimension ofstudying health vs. disease and drug response.4:00 Sponsored Presentation Sponsored bySpeaker to be Announced4:20-5:00 Sponsorship Opportunities AvailableContact: Ilana Quigley(781) 972-5457 | iquigley@healthtech.com5:00 Welcome Reception in the Exhibit Hall with Poster Viewing6:00-9:00 Dinner Short Course* (see page 2 for details)SC2: Automating a 3-D Culture Screening Laboratory:Meeting the ChallengesInstructors to be Announced*Separate registration requiredTuesday, October 297:30 am Breakfast Presentation (Sponsorship OpportunityAvailable) or Morning Coffee3-D Models for Drug Screening8:30 Chairperson’s Opening Remarks8:35Tissue Models of Disease andTheir Potential for High-Throughput ScreeningVictoria M. Virador, Ph.D., Staff Scientist, Center for Cancer Research,National Cancer Institute, NIHA standard, simplified in vitro three-dimensional tissue model will be aninvaluable tool for mimicking the biology of living tissues, studying thecomplexity added by disease and testing drug candidates.Thanks to fruitfulcollaborations between biologists, physicists and engineers, cell-based assaysare expanding into the realm of tissue analysis. Accordingly, three-dimensional(3-D) micro-organoid systems will play an increasing role in drug testing andtherapeutics over the next decade. Nevertheless, important hurdles remainbefore these models are fully developed for high-throughput screening (HTS).Modeling 3-D tissues to mimic in vivo architecture remains a major challenge.I will highlight recent breakthroughs in the field of tissue bioengineering aimedat enhancing the success of drug candidates through preclinical optimization. Ifocus on three-dimensional models by tissue or organ type with an emphasison how faithful the model is to tissue architecture and functionality, and thenI explore models that are most amenable to high-throughput screening withemphasis on detection platforms and data modeling. As technology advancesto provide novel 3-D methods of HTS analysis, so do their potential pitfalls.9:05 Alginate-Based 3-D Cell Culture System as an in vitroTumorModel for Anticancer StudiesMandip Sachdeva, Ph.D., Professor, College of Pharmacy and PharmaceuticalSciences, Florida A&M UniversityThree-dimensional (3-D) in vitro cultures are recognized for recapitulating thephysiological microenvironment and exhibiting high concordance with in vivoconditions. We have developed an alginate-based scaffold as an in vitro tumormodel for anticancer drug screening and to track nanoparticle penetration.NSCLC stem cells were developed as 3-D in vitro tumor models. The effect ofanticancer drugs/nanoparticles were studied and compared with parental cellsand stem cell monolayer cultures. The effect of anticancer drugs on apoptosisinduction and other antiapoptotic markers were also studied and comparedwith the 2-D cell culture systems.9:35 Inhibition of KRAS-DrivenTumorigenicity by Interruptionof an Autocrine Cytokine CircuitAmir Aref, Ph.D., Research Fellow, Cancer Biology, Dana-Farber CancerInstitute, Harvard Medical SchoolModels for disease processes are critical for improving understanding anddeveloping new therapeutics. Microfluidic assays provide unique capabilitiesfor mimicking the local microenvironment in terms of multiple cell types andfor controlling and monitoring chemical gradients and cellular interactions.We present a new model to simulate the epithelial-mesenchymal transition,a critical stage in metastatic cancer, and use it to examine differences in drugresponse between 2-D and 3-D, monoculture and co-culture. These studiesreveal this approach’s potential in identifying new drug targets that mightprevent metastatic disease.10:05 Coffee Break in the Exhibit Hall with Poster Viewing10:45 Bioengineering Functional HumanTrabecular MeshworkOutflow Systems for Anti-Glaucoma Drug ScreeningYubing Xie, Ph.D., Assistant Professor, College of Nanoscale Science andEngineering, University at Albany-SUNYGlaucoma is the leading cause of irreversible blindness, resulting from elevatedintraocular pressure (IOP).The current unmet need in the field is a proper invitro model system that can be used to study outflow physiology and identifyIOP-lowering agent. Based on our patented technology, we have successfullydemonstrated the feasibility of recreating functional human trabecularmeshwork (HTM) on micropatterned, porous scaffolds and performing outflowstudies and drug testing using the bioengineered HTM. Our results show thatbioengineered HTM exhibited in vivo-like morphology, expression of HTMmarkers, outflow characteristics and drug responsiveness.This in vitro HTMmodel system provides a new avenue for understanding HTM physiology andpharmaceutical screening of anti-glaucoma therapeutics.11:15 Drug Uptake and Diffusion in 3-D Multicellular MicrotissuesJeffrey Morgan, Ph.D., Professor, Medical Science and Engineering andCo-Director, Center for Biomedical Engineering, Brown UniversityMy lab has developed an easy-to-use format for the formation of scaffold-free multicellular spheroids. We’ve devised new algorithms to quantitativelystudy 3-D drug transport in vitro. We are investigating the role of drug effluxtransporters, such as P-glycoprotein (Pgp), and the effects of inhibitors ofPgp on the 3-D uptake and diffusion of drugs through the multiple cell layersof a spheroid. Some inhibitors of Pgp also inhibit gap junctions, an activitynot previously reported for these drugs. Multicellular spheroids are bettermimics of the in vivo environment because their cell density is closer to thatof real tissues and they better replicate the in vivo barriers to drug uptake anddiffusion.This 3-D model is useful for many cell types like cancer cell lines,stem cells and human cells. Drug uptake and diffusion are key for efficacy andpotential toxicity of all drugs.The audience will learn of a new 3-D technology,new algorithms to quantitatively study 3-D drug transport in vitro and neweffects of well-known drugs that can only be uncovered with a 3-D system.11:45TalkTitle to be AnnouncedMichael Atkinson, Ph.D., Coordinator and Leader of Workpackage 01, Instituteof Radiation Biology, German Research Center for Environmental Health,Technical University Munich3-D tumor spheroids have been used as relevant biological modelsfor oncology drug discovery for many years. However, aside fromchemotherapeutic interventions, these 3-D models are also highly valuabletools for emulating radiotherapy in vitro. In the presentation, the noveluse of tumor co-culture spheroids for assessing combined chemo- andradiotherapeutic intervention will be illustrated. High-content analyticalreadouts are used to discriminate between the different cell populations inthe 3-D microtissues to quantify the therapeutic impact on them.12:15 pm Close of Engineering Functional 3-DTissueModels Meeting
  6. 6. FASTCONGRESS.com6October28-29 Phenotypic Drug DiscoveryPhenotypic Drug DiscoveryMaximizing Information in Early Drug Discovery for Better Target and Drug SelectionInauguralMonday, October 287:30 am Main Conference Registration and Morning CoffeeAdvantage of Phenotypic Drug Discovery8:15 Chairperson’s Opening Remarks8:30The Contribution of Mechanistic Understanding toPhenotypic Screening for First-in-Class MedicinesDavid C. Swinney, Ph.D., CEO, Institute for Rare and Neglected DiseasesDrug Discovery (iRND3)The level of mechanistic understanding required for drug discovery is a centralfeature of most strategies. Paradoxically, an understanding of mechanismis not required for regulatory approval. Recent analysis of how medicineswere discovered showed that some mechanistic understanding was used toselect starting points in the majority of successful phenotypic drug discoveryprograms. It was concluded that mechanism takes on different connotationsdepending on context and perspective, and that a target need not be theexclusive definition of mechanism.8:55 Integrating NovelTechnologies to Identify Small Moleculesthat DriveTranslational Research andTherapeuticsMichelle Palmer, Ph.D., Director, Discovery and Preclinical Research,Broad Institute9:20 Systematic Repositioning of Drugs Using PhenotypicScreening DataMark Hurle, Ph.D., Senior Investigator, Bioinformatics and ComputationalBiology, GlaxoSmithKlineComputational analysis of phenotypic screening data is often geared towardanalysis of results from a single screen, identifying targets via annotation ofthe compounds hit. Hits are also commonly defined via change in a singlemeasurable. By utilizing large numbers of screens and/or measurables,commonalities between targets and phenotypes can be detected. Twoexamples will be discussed: Connectivity Map, which utilizes genome-wideexpression data, and CRUSH (Compound Repositioning Using ScreeningHits), which analyzes high-throughput and focused screening data.These pipelines lead to repositioning of compounds and targets againstadditional diseases.9:45 Coffee BreakHigh-Content Analysis10:15The Role of HCA in Quantitative Systems PharmacologyD. Lansing Taylor, Ph.D., Director, University of Pittsburgh Drug DiscoveryInstitute and Allegheny Foundation; Professor, Computational and SystemsBiology, University of Pittsburgh10:40 High-Content and High-Definition Screenings IdentifiedStem Cell RegulatorsSheng Ding, Ph.D., William K. Bowes, Jr. Distinguished Investigator,Gladstone Institutes; Professor, Pharmaceutical Chemistry, UCSFRecent advances in stem cell biology may make possible new approachesfor treatment of a number of diseases. A better understanding of molecularmechanisms that control stem cell fate/function as well as an improved abilityto manipulate them is required. Toward these goals, we have developed andimplemented high-content and high-definition cell-based screens of chemicallibraries to identify and further characterize small molecules that can controlstem cell fate in various systems. This talk will provide latest examples ofdiscovery efforts in my lab that have advanced our ability and understandingtoward controlling stem cell fate.11:05 A One-Step High-Content Imaging Assay to MonitorApoptosis and Cell Cycle State in Mammalian CellsCaroline Shamu, Ph.D., Lecturer, Systems Biology and Director,ICCB-Longwood, Harvard Medical School11:30 Sponsored Presentations (Opportunities Available. Contact IlanaQuigley at 781-972-5457 or iquigley@healthtech.com.)12:00 pm Luncheon Presentation: Sponsored byThe BioMAP® Platform of Primary Human CellSystems for Phenotypic Drug Discovery andDevelopment – Lessons LearnedEllen L. Berg, Ph.D., General Manager and Scientific Director, BioSeek,a division of DiscoveRxThe BioMAP® platform of primary human cell-based disease models hasbeen used since 2004 by companies, academics and the government toprofile small molecules, natural products and biologics. From this experience,we have developed guidelines and best practices for the use of these assaysin phenotypic drug discovery. Key applications that will be presented includethe use of this platform to identify compounds that are more likely to progressin development and for deconvolution of compound mechanisms of action.Phenotypic Screening inPhysiologically-Relevant Models1:30 Chairperson’s Opening Remarks1:35 Phenotypic Screening and Profiling in IncreasinglyPhysiologically-Relevant ContextsAnne Carpenter, Ph.D., Director, Imaging Platform, Broad InstituteShantanu Singh, Ph.D., Postdoctoral Researcher, Broad InstituteOur laboratory works with dozens of collaborators worldwide to designand execute large-scale microscopy-based experiments to identify causesand potential cures of disease. Physiologically-relevant model systems areincreasingly being used in this work, including co-cultures of two different celltypes to better mimic functional tissue and whole organisms such as Caenorhabditis elegans to study entire organ systems. Machine-learning approaches,in some cases guided by biologists’ intuition, have been successfully used tomeasure subtle phenotypes in these complex model systems.2:00 Expanding the Use of Primary Cell Systems in HitIdentification and Compound ProfilingSteve Ludbrook, Ph.D., Section Head, Screening and Compound Profiling,GlaxoSmithKlineThe current focus on translationally-aligned drug discovery approaches,together with significant technology improvements, offers the potential toaccelerate the uptake of primary cell screening systems in the drug discoveryprocess. Examples of primary cell systems will be described, encompassingthe increased usage of phenotypic assays in specific program critical pathactivities, but also primary screening activities for hit identification, with theaim of improving translation from the screening plate to the diseased patient.Phenotypic screening (aka classical pharmacology) has been historically used in drug discovery. While technological developments have made the prevalenceof target-based screening more popular, statistical analysis shows that a disproportionate number of first-in-class drugs with novel mechanisms of actioncome from phenotypic screening. Cambridge Healthtech Institute’s Inaugural Phenotypic Drug Discovery meeting will address the advantages of phenotypicscreening vs. target-based screening, and focus on assay development, selection of physiologically-relevant models and subsequent target identification.
  7. 7. Phenotypic Drug DiscoveryFunctional Analysis & Screening Technologies Congress 72:25 Human Induced Pluripotent Stem Cells and Patient SpecificCell-Based Disease Models for Drug DiscoveryAnne Bang, Ph.D., Director, Cell Biology, Sanford-Burnham Medical ResearchInstitutePatient-specific primary cells and human induced pluripotent stem cells(hiPSC) could aid in the development of clinically useful compounds. Weused patient cells to develop a phenotypic assay for muscular dystrophy andconducted a high-content screen with the goals of identifying early treatmentcandidates. In addition, using hiPSC derived neurons, we performed a high-content screen for compounds that modulate neurite growth. We will discussour high-content screening results and development of hiPSC based models.2:50 Sponsored Presentation (Opportunity Available. Contact IlanaQuigley at 781-972-5457 or iquigley@healthtech.com.)3:05 Refreshment Break in the Exhibit Hall with Poster Viewing4:00 Identifying Cardioprotectants of an Ischemia-ReperfusionModel in iPSC-Derived CardiomyocytesSiobhan Malany, Ph.D. Chemical Biology Team Leader, Sanford-BurnhamMedical Research InstituteSmall molecules that protect cardiac cells from ischemia-reperfusionmediated death would potentially limit heart damage during heart attack.We have developed a 1536-well high-throughput phenotypic acute cell-based model of ischemia and reperfusion injury in human iPSC-derivedcardiomyocytes (iCells). Hydrogen peroxide treatment simulates the oxidativestress of reperfusion and 2-deoxy-D-glucose simulates the metabolic stress ofischemia. We screened known drug collections for their ability to protect iCellsagainst cell death in a viability assay to better understand pathways involved.4:25 HCS to Discover RNATherapeutics for Heart FailureMark Mercola, Ph.D., Professor, Bioengineering, UCSD; Professor andDirector, Muscle Development and Regeneration Program, Sanford-BurnhamMedical Research InstituteThere is an urgent need for therapies that reverse the course of ventriculardysfunction in heart failure, which is a leading cause of morbidity andmortality. Our research is focused on developing high-content screeningassays and instrumentation to discover targets and screen for moleculesactive in cardiac regeneration and cardiomyocyte contractility. HCS thatincorporates static and kinetic (live imaging) endpoints were used to developa potential RNA therapeutic for heart failure that targets a clinically validatedprotein and shows efficacy in a mouse model.5:00 Welcome Reception in the Exhibit Hall with Poster Viewing6:00-9:00 Dinner Short Course* (see page 2 for details)SC3: Introduction to High-Content Phenotypic ScreeningInstructor: Anthony M. Davies, Ph.D., Director, Irish National Centerfor High-Content Screening and Analysis (INCHA)*Separate registration requiredTuesday, October 297:30 am Breakfast Presentation (Sponsorship Opportunity Available)or Morning CoffeeChemical Genomics8:30 Chairperson’s Opening Remarks8:35 Coincidence Biocircuits for the Interrogation of ComplexChemical LibrariesJames Inglese, Ph.D., National Center for AdvancingTranslational Sciences, NIHHigh-throughput screening, a mainstay of pharmaceutical drug discovery, usesmicro-volume assays to interrogate chemical libraries. Reporter gene assays,well-suited for HTS, can offer a wealth of cellular pathways to target; however,existing designs are prone to numerous reporter-based artifacts exacerbatedby the use of complex chemical libraries such as natural product extracts.Through evaluating the basis of these ‘off-pathway’ effects we have devisedan approach to improve the fidelity and efficiency of reporter gene-based HTS.9:00 Chemogenomics Library Screen Reveals a Novel Mechanismfor Modulating ApoE Levels in the BrainFabien Vincent, Ph.D., Associate Research Fellow, Assay Development andPharmacology, PfizerA strong genetic link exists between the ApoE4 genotype and Alzheimer’sDisease (AD). A loss of function hypothesis is gaining credence andaccordingly mechanisms leading to increased production and secretion ofApoE in the brain may be therapeutically beneficial. A proprietary librarytermed the Chemogenomics Library was designed for the purpose ofidentifying novel targets and mechanisms using phenotypic screening.The screen revealed HDAC inhibition as a novel mechanism for enhancedApoE secretion. Importantly, oral administration of HDAC inhibitor MS275to mice led to a significant increase in ApoE levels in both plasma and thehippocampus, thus validating this novel mechanism in vivo.9:25 Chemical Genetics Reveals a Kinase-Independent Role forProtein Kinase R in PyroptosisErik Hett, Ph.D., Senior Scientist, MedChem, PfizerFormation of the inflammasome, a scaffolding complex that activatescaspase-1, is important in numerous diseases. Pyroptotic cell death inducedby anthrax lethal toxin (LT) is a model for inflammasome-mediated caspase-1activation. We discovered 7-desacetoxy-6,7-dehydrogedunin (7DG) in aphenotypic screen as a small molecule that protects macrophages fromLT-induced death. Using chemical proteomics, we identified protein kinaseR (PKR) as the target of 7DG and show that RNAi knockdown of PKRphenocopies treatment with 7DG. Further, we show that PKR’s role in ASCassembly and caspase-1 activation induced by several different inflammasomestimuli is independent of PKR’s kinase activity.9:50 Sponsored Presentation (Opportunity Available. Contact IlanaQuigley at 781-972-5457 or iquigley@healthtech.com.)10:05 Coffee Break in the Exhibit Hall with Poster ViewingCase Studies in Phenotypic Drug Discovery10:45 Phenotypic Screening for Lipid Droplet ModulatorsZhuyin (Julie) Li, Ph.D., Biology Team Leader, Division of Pre-ClinicalInnovation, National Center for Advancing Translational Sciences, NIHIntracellular lipid droplets are associated with many dysfunctions such asobesity, coronary artery disease, fatty liver disease, and infectious diseases.There are limited medical interventions that could be used to treat theseconditions. We have developed a lipid droplet accumulation phenotypicassay using embryonic Drosophila S3 cells, and utilized the assay to conductaquantitative HTS against 400K compounds. Many hits found from thescreening demonstrated efficacy in mammalian cells as well.11:10 Inhibition of the c-Myc Oncoprotein with a Naturally-Occurring Compound and Its AnalogsEdward Prochownik, M.D., Ph.D., Director, Oncology Research, Children’sHospital of PittsburghMost cancers deregulate the c-Myc (Myc) oncoprotein, which sustainstumor proliferation. This bHLH-ZIP transcription factor interacts with anotherbHLH-ZIP protein, Max, to regulate transcription. We have developed smallmolecule Myc-Max disruptors (“Myc compounds”) that inhibit tumor cellproliferation although poor pharmacokinetics limit their in vivo efficacy. Wehave now identified a promising, naturally-occurring Myc compound andgenerated several analogs with improved activity while eliminating a highlyreactive chemical group, thus improving specificity. These analogs are highlybio-available, well-tolerated and possess significant anti-tumor effects.11:35 From Phenotypic Screening to Mechanism of Action:WhatDoes theToolbox Look Like?Monica Schenone, Ph.D., Research Scientist, Broad InstituteAs the biopharmaceutical industry moves from target-based into phenotypicscreening of small molecules, elucidating mechanism of action (MoA) iscrucial. However, determining the MoA of small molecules identified fromphenotypic screens remains a challenge. The tool box for target identificationincludes direct biochemical methods, genetic interactions and computationalinference. In many cases, combinations of approaches may be required tofully understand mechanisms of small-molecule action.12:00 pm Close of Phenotypic Drug Discovery Meeting
  8. 8. FASTCONGRESS.com8Screening and FunctionalAnalysis of 3-D ModelsOctober29-30 Screening and FunctionalAnalysis of 3-D ModelsComplex Cellular Models Predictive of Human Response to Improve Early Decision MakingInauguralTuesday, October 2912:00 pm Main Conference RegistrationCompound Characterization with 3-D Models1:30 Chairperson’s Opening Remarks1:35 Application of Clonogenic 3-D Assays in High-ThroughputScreening and Compound Optimization/CharacterizationAaron Morris, Ph.D., Lab Head, Cancer Biology, Sanofi OncologyThe ability to grow in an anchorage-independent manner is a hallmark ofcancer cells. A 3-dimensional clonogenic growth assay in soft agar leveragesthis phenotype for assessment of cancer-signaling dependencies. We haveperformed a 3-D multi-cell line parallel phenotypic high-throughput screenwith our proprietary compound collection to identify pathways, targets andchemical matter with selective anti-tumor activity. This 3-D soft agar assay hasbeen further optimized to support hit-to-lead optimization efforts and a fullrange of MoA characterization studies.2:00 High-Throughput 3-D Cell Culture for Drug Discovery andHumanToxicologyJonathan Dordick, Ph.D., Isermann Professor of Chemical and BiologicalEngineering, and Vice President for Research, Rensselaer Polytechnic InstituteThe need for increased knowledge of drug candidates at early stages ofdiscovery is driving the development of new, high-throughput, and high-content technologies. The centerpiece of our approach involves the use of aminiaturized three-dimensional mammalian cell culture platform that consistsof 500-1,000 individual cell cultures on a microscope-size slide “biochip.” Abroad range of human and animal cells have been used on the chip platform,including primary cells and transformed cell lines from multiple tissues, aswell as human and animal stem cells. Furthermore, many assays that aretraditionally performed in well plates can be adapted to the high-throughput3-D cell culture chip.2:25 Development Challenges with 3-DTumor Spheroid Cultureand Endpoint Measurements Relevant to Drug ScreeningMartina Fitzek, Associate Principal Scientist, Discovery Sciences, AstraZenecaThe pharmaceutical industry faces increasing pressure to deliver noveldifferentiated products to fulfill unmet medical needs. We have seen atrend towards increased interest in the use of physiologically-relevantsystems applied to drug screening campaigns. Emerging techniques inthe 3-D culture area can position cells in an environment which offers thepotential for measuring more relevant functional responses. We will describeour experience using different techniques to generate tumor cell-derivedspheroids and the methods we have applied to measure their properties.The presentation will be an assessment of the potential benefits and thechallenges that need to be overcome to successfully exploit the morephysiologically-relevant properties of tumor spheroids and implications forfuture drug screening.2:50 Sponsored Presentations (Opportunities Available. Contact IlanaQuigley at 781-972-5457 or iquigley@healthtech.com.)3:20 Refreshment Break in the Exhibit Hall with Poster ViewingHigh-Content Analysis of 3-D Models4:15 Development of a Novel Reversible Cell Scaffold (RCS)System for Use with High-Content Imaging PlatformsAnthony M. Davies, Ph.D., Director, Irish National Center for High-ContentScreening and Analysis (INCHA)In this presentation we will for the first time showcase a completely novelsystem of cell culture permitting cells to be first grown in 3-D and thenharvested as required. This system has been specifically designed for usewith HCS/A imaging platforms, automated liquid handling and HTS. Unlikeany other 3-D assay systems currently used, our technology does not relyupon solid gel matrices, scaffolds, micro-patterned surfaces or hanging dropassay systems to achieve reproducible cancer spheroid growth. Indeedmany of the inherent technical issues surrounding these technologies areavoided by utilizing this novel 3-D culture technology. This reversible cellscaffold system comprises of two individual components: (i) a low-viscosityliquid support/scaffold; and (ii) an agent that deactivates the scaffold,permitting sedimentation of cellular structures under gravity, permitting eitherhigh-content imaging in situ or recovery for further analysis such as geneexpression or biochemical analysis. This system of suspension/deactivationhas been used to great effect in both high-content imaging and subsequentgene expression studies.4:40 3-D Models of Metastatic CancerTargetingTumor-InitiatingCells via High-Content AnalysisDaniel V. LaBarbera, Ph.D., Assistant Professor, Pharmaceutical Sciences,Skaggs School of Pharmacy and Pharmaceutical Sciences, University ofColoradoIn vitro 3-D models, particularly multicellular tumor spheroids (MCTS), offera systems biology approach to bridge information from molecular target and2-D cell-based screening, with in vivo models, to improve the predictability ofdrug discovery. We will discuss our current research with 3-D models usingfluorescent reporter models, suitable for high-content imaging drug discovery.Specifically, we will describe methods to measure local (single-cell) and global(entire MCTS) changes after small molecule treatment targeting drug resistantinvasive phenotypes of cancer.5:05 Rapid and Automated Multidimensional FluorescenceMicroscopy Profiling of 3-D Human Breast CulturesSylvain Costes, Ph.D., Principal Investigator, Cancer and DNA DamageResponse, Lawrence Berkeley National LaboratoryThree-dimensional (3-D) tissue culture provides a physiologically-relevantmicroenvironment for testing cancer therapies. Response to therapiesmeasured in 3-D cultures correlates better with patient response than classic2-D screenings. However, biological measurements in 3-D culture are slowand difficult due to 3-D image acquisition and analysis. By combining samplesmearing techniques with high-throughput 2-D scanning, we introducean experimental protocol allowing accurate and rapid quantification of 3-Dcultures. Multiple 3-D imaging features integrated into hierarchical clusteringclassification show promising results.While more informative than cell-free biochemical assays, monolayer or suspension cell culture HTS assays still fail to accurately reflect the human cellularmicroenvironment.There is a need for physiologically-relevant cellular models for drug screening and functional analysis that provide high predictive value for clinicalefficacy and safety of compounds.The three-dimensional cell culture models mimic the human tissue microenvironment and provide more accurate information forcompound and target selection, thereby reducing late-stage attrition. Cambridge Healthtech Institute’s Inaugural Screening and Functional Analysis of 3-D Modelsmeeting will explore the use of 3-D models to profile compound action and predict toxicity and efficacy.The meeting will cover assay development using 3-D cellularmodels, high-content analysis and imaging of 3-D models, and applications of screening 3-D models for compound profiling and target discovery/validation.
  9. 9. Functional Analysis & Screening Technologies Congress 96:00-9:00 Dinner ExpertThinkTank* (see page 2 for details)SC4: How to Meet the Need for Physiologically-Relevant Assays?Moderator: Lisa Minor, Ph.D., President, In Vitro Strategies, LLCPanelists:Anne Bang, Ph.D., Director, Cell Biology, Sanford-Burnham MedicalResearch InstituteAnthony M. Davies, Ph.D., Director, Irish National Center for High-ContentScreening and Analysis (INCHA)Marina Fitzek, Associate Principal Scientist, Discovery Sciences, AstraZenecaAaron Morris, Ph.D., Lab Head, Cancer Biology, Sanofi OncologyMichelle Palmer, Ph.D., Director, Discovery and Preclinical Research,Broad InstituteCaroline Shamu, Ph.D., Lecturer, Systems Biology and Director, ICCB-Longwood, Harvard Medical SchoolD. Lansing Taylor, Ph.D., Director, University of Pittsburgh Drug DiscoveryInstitute and Allegheny Foundation; Professor, Computational and SystemsBiology, University of Pittsburgh*Separate registration requiredWEDNEsday, October 307:30 am Breakfast Presentation (Sponsorship Opportunity Available)or Morning CoffeeFunctional Analysis andTargetID/Validation with 3-D Models8:25 Chairperson’s Opening Remarks8:30 Functional Analysis ofTherapeutic Antibodies Usingex vivoTumor SpheroidsMitchell Ho, Ph.D., Chief, Antibody Therapy Section, Laboratory of MolecularBiology, National Cancer Institute, NIHTumor microenvironments present significant barriers to antibody therapy.We established ex vivo tumor spheroids to study molecular mechanismsof antibody drug resistance. The tumor spheroids may prove invaluable foridentifying potential targets in addition to providing an innovative platform foranalyzing therapeutic antibodies. We compared the global gene expressionprofiles of spheroids and monolayers and identified genes specific to the3-D biological structure of mesothelioma. An update on generation of humansingle-domain antibodies for cancer therapy will also be discussed.8:55Third Dimension:The Future of RNAi-DrivenTargetIdentification in CancerGeoffrey A. Bartholomeusz, Ph.D., Assistant Professor and Director, siRNACore Facility, Department of Experimental Therapeutics, Division of CancerMedicine, University of Texas MD Anderson Cancer Center3-D spheroid cell cultures, unlike 2-D monolayer cell cultures, demonstrateproperties that are highly co-related to tumors. The ease at which spheroidmodels can be applied in high-throughput screens has resulted in therealization of their importance to address relevant questions in tumorbiology. We are developing 3-D spheroid cell culture models to be used inhigh-throughput screening, and the design of one such model for targetidentification utilizing high-throughput RNAi screens will be discussed.9:20 Identification ofTherapeuticTargets in 3-Dimensional Patient-DerivedTumor Spheroids with Cancer Stem Cell CharacteristicsFredika M. Robertson, Ph.D., Professor, Experimental Therapeutics, Center forTargeted Therapy; Director, Translational Therapeutics Laboratory, University ofTexas MD Anderson Cancer CenterTumor cells isolated from breast cancer patients with metastatic diseasemanifested by pleural effusion spontaneously form 3-D tumor aggregatesthat retain characteristics of tumor initiating cells/cancer stem cells. Thispresentation will discuss the use of a combination of analytical platformsincluding high-content live-cell imaging, confocal microscopy, flow cytometry,and histological approaches for phenotypic analysis of tumor spheroidsthat serve as surrogates of metastasis. These approaches provide us withpowerful tools to identify those patients who may benefit from inclusioninto clinical trials for new therapeutics under development. The use of theseapproaches to identify specific signaling pathways and molecular drivers ofdisease progression will also be discussed.9:45 A 3-D Culture-Based siRNA ScreeningTool for SecretoryEpithelium CancerTargetsNathalie Picollet-D’Hahan, Ph.D., Senior Researcher, iRTSV/Biomics, CEAGenetic screening is certainly one of the most powerful approaches to gaininsights into gene function and complex biological processes. However, it isbecoming evident that functional genomics screens need to be performedin a more physiologically-relevant environment provided by a 3-D context.We propose to combine two technological innovations, both in microfluidic-generated 3-D cultures and parallelized lens-less imaging to perform 3-DRNAi-based HTS and to characterize new biomarkers in prostate cancer. Weemployed silencing RNAs (siRNA), targeting kinase-related genes to identify3-D-specific effectors of prostate acini morphogenesis and polarity.10:10 Sponsored Presentation (Opportunity Available. Contact IlanaQuigley at 781-972-5457 or iquigley@healthtech.com.)10:25 Coffee Break in the Exhibit Hall with Poster ViewingComplex Models ofTumor Microenvironment11:15 Engineering 3-D in vitroTumor Models of AntineoplasticDrug Resistance: Use of Malignant Spheroids and Non-MalignantAccessory Cells from the Metastatic MicroenvironmentEugen Dhimolea, Ph.D., Research Fellow, Medical Oncology, Dana FarberCancer Institute, Harvard Medical SchoolTo model the composition and architecture of metastatic lesions and toaddress the role of the local metastatic microenvironment in the drugresistance exhibited by disseminated cancers, we assembled heterotypic invitro 3-D tissue cultures comprised of malignant cells growing in dispersedformat vs. growing as spheroids, and in the presence vs. absence of non-malignant accessory cells from organs frequently targeted by metastaticdisease. We assessed the pathophysiological relevance of these models bytesting the activity of more than 100 FDA-approved antineoplastic drugs. Thespheroid morphology significantly decreased the efficacy for several classesof conventional DNA-damaging (e.g. anthracyclins) agents as well as recentlyestablished targeted therapies (e.g. kinase inhibitors), while being associatedwith increased cell-killing activity of others. Our 3-D co-culture systemprovides a practical and clinically-relevant experimental system to study themechanisms of metastatic microenvironment-related drug resistance and toscreen for biologically active compounds that circumvent it.11:40Tumor-Microenvironment-on-Chip (TMOC)Bumsoo Han, Ph.D., Associate Professor, Mechanical and BiomedicalEngineering, Purdue UniversityTargeted delivery of therapeutic and imaging agents to tumors withoutnon-specific accumulation at normal tissues can significantly improve thetreatment and diagnosis of cancers. Nanotechnology recently enabledvarious functional nanoparticles as vehicles for targeted delivery. However,it is extremely challenging to optimize their design and configuration usingtraditional cell culture and animal models. In order to address this challenge,a new in vitro model was developed to simulate the complex 3-D tumormicroenvironments relevant to the transport of nanoparticles.12:05 pmThree-Dimensional Melanoma Models: From Screeningto Skin ReconstructsAdina Vultur, Ph.D., Staff Scientist, Wistar InstituteThe melanoma field has seen unprecedented clinical successes in the last fewyears; however, tumor heterogeneity and plasticity indicate the requirementfor an arsenal of therapeutic strategies to overcome advanced disease. Wefocus our efforts on investigating genetically-distinct melanoma subgroupsusing high-throughput 3-D screening assays (with and without a supportmatrix) and increasingly complex preclinical models from normal human skinreconstructs to patient-derived xenografts. Our melanoma model pipeline hasalready allowed us to identify compounds and targets with limited activity inthe 2-D setting, but with potential in vivo.12:30 Close of Screening and Functional Analysis of 3-D ModelsMeeting
  10. 10. FASTCONGRESS.com10Physiologically-Relevant CellularTumor Models for Drug DiscoveryOctober29-30Physiologically-Relevant CellularTumor Models for Drug DiscoveryIn vitro Models of Tumor Microenvironment for New Cancer Target and Drug DiscoveryTuesday, October 2912:00 pm Main Conference RegistrationComplexTumor Models for Phenotypic Assays1:30 Chairperson’s Opening Remarks1:35 A Quantitative and Reproducible High-ThroughputPhenotypic-Based Angiogenesis Assay as a Primary Screenfor Angiogenesis InhibitorsMohanraj Dhanabal, Ph.D., Group Leader, Lead DiscoveryTechnology,EMD SeronoAngiogenesis, the formation of new blood vessels from the pre-existingmicrovasculature, is among the key events for many physiological andpathological processes. We describe an angiogenesis assay system that allowsrapid and reliable quantification of three-dimensional vessel formation in-vitroin a miniaturized format using (BD Matrigel™) onto 384 plates. Such platformis used for screening compounds in a 384-well plate format to a High ContentScreening. Finally, we used this to screen more compounds during the drugdiscovery and development process, which led us to the identification andprioritization of compounds with potent antiangiogenic activity.2:00 BioDynamic Imaging ofThree-Dimensional Drug Response inSpheroids and CancerTissueDavid Nolte, Ph.D., Professor, Physics, Purdue UniversityBioDynamic Imaging is a new form of three-dimensional functional imaging. Itdetects intracellular motions that act as a suite of biomarkers and provides anendogenous form of image contrast inside living tissue. Heterogeneous three-dimensional drug response affecting diverse intracellular motions is mappedout in real time after application of drugs. Delayed penetration, internal hypoxia,quiescent cell populations, and differential responses are captured. Correlationof the dynamic signatures with conventional high-content analysis providesinsight into the mechanistic origins of the dynamic images.2:25 A Chemical Biology Approach to Identify New MicrotubulesDynamics RegulatorsLaurence Lafanechère, Ph.D., CNRS Research Director, Department of CellDifferentiation andTransformation, Institut Albert BonniotThe emergence of tumor resistance to conventional microtubule-targeting drugsrestricts their clinical use. Using a cell-based assay that recognizes microtubulepolymerization status to screen for chemicals that interact with regulators ofmicrotubule dynamics, we identified Pyr1, a cell permeable inhibitor of LIMKinase, which is the enzyme that phosphorylates and inactivates the actindepolymerizing factor cofilin. Pyr1 reversibly stabilized microtubules, blockedactin microfilament dynamics, and inhibited cell motility in vitro. Pyr1 inhibitionof LIM Kinase caused a microtubule stabilizing effect, which was independentof any direct effects on the actin cytoskeleton.Thus, LIM Kinase functions as asignaling node that controls both actin and microtubule dynamics. In addition,Pyr1 retained its activity in multidrug resistant cancer cells that were resistantto conventional microtubule targeting agents. It is also effective in animals,where it delays tumors formation while showing a good tolerability.Thus, Pyr1is a “first in class” LIMK inhibitor, showing efficacy on mice tumor models.Our results show that LIMK, which is an emerging target for cancer therapy, isindeed a targetable enzyme for cancer treatment.2:50 Sponsored Presentations (Opportunities Available. Contact IlanaQuigley at 781-972-5457 or iquigley@healthtech.com.)3:20 Refreshment Break in the Exhibit Hall with PosterViewingOrganotypic Co-CultureTumor Models4:15 4-D Co-Culture Models of Breast Cancer forTarget IdentificationRay Mattingly, Ph.D., Professor, Pharmacology, Wayne State UniversityWe have developed 3-D coculture models that we term MAME (mammaryarchitecture and microenvironment engineering).These MAME models includetumor cells cocultured with a variety of other elevant subtypes, includingmyoepithelial cells, tumor-associated fibroblasts and macrophages, andendothelial cells of blood and lymphatic origin. Proteolysis can be imagedand quantified using a live-cell assay of the degradation of fluorescently-quenched collagens. Extension of these models into 4-D (3-D plus time)demonstrates processes such as development of positive feedback loopsbetween the cocultured cells, invasion of tumor cells into the angiogenic andlymphangiogenic networks, and allows identification of targets through profilingof cytokine production and responses.4:40 A Stromal-Based 3-D Co-Culture Model for ChemotherapySensitivityTestingOmar S. Aljitawi, M.D., Assistant Professor, Internal Medicine, University ofKansas Medical CenterThe discrepancy in leukemic cell responses to chemotherapy in vivo,compared to in vitro, is partly related to the interactions of leukemic cells withthe 3 dimensional (3-D) bone marrow (BM) stromal microenvironment. Wedescribe an in vitro model that we have developed to investigate the effectsof chemotherapy on leukemic cell lines co-cultured with human BM stromalcells in 3-D.This novel model provides an opportunity to study leukemic cellresponses to chemotherapy in 3-D.5:05 Micropatterned Surfaces for the Study of Cancer andEndothelial Cell Interactions with Hyaluronic AcidSharon Gerecht, Ph.D., Associate Professor, Chemical and BiomolecularEngineering, Johns Hopkins UniversityHyaluronic acid (HA) has been implicated in cellular interactions that areassociated with cancer progression. Functional HA surfaces were developedto study interactions between cancer cells and HA. A similar surface patterningapproach was used to create HA regions next to fibronectin in two- andthree- dimensional settings to study the interactions between cancer andendothelial cells.The ability to observe the dynamic interactions of cancer cellsand angiogenesis within HA–rich microenvironment will improve fundamentalunderstanding towards therapeutic targets.InauguralTraditional drug screening relies on monolayer cell culture, which is not always predictive of natural physiological state.This is especially problematic in cancer drugdiscovery, where simple cell cultures are not predictive of a complex tumor microenvironment that consists of various cell types that interact in three-dimensionalstructures. As the cost of drug development rises, there is increasing pressure for more predictive in vitro models for functional analysis and compoundcharacterization. Cambridge Healthtech Institute’s Inaugural Physiologically-Relevant CellularTumor Models for Drug Discovery meeting will focus on the latestadvances in 3-D cellular tumor models and complex co-culture systems for functional analysis studies and compound screening/characterization.• Your poster will be available to 150+ 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• Please visit www.FASTcongress.com for poster instructions and deadlinesGain Further Exposure:Present a Poster and Save $50
  11. 11. 11Functional Analysis & Screening Technologies Congress6:00-9:00 Dinner ExpertThinkTank* (see page 2 for details)SC4: How to Meet the Need for Physiologically-Relevant Assays?Moderator: Lisa Minor, Ph.D., President, In Vitro Strategies, LLCPanelists:Anne Bang, Ph.D., Director, Cell Biology, Sanford-Burnham MedicalResearch InstituteAnthony M. Davies, Ph.D., Director, Irish National Center for High-ContentScreening and Analysis (INCHA)Marina Fitzek, Associate Principal Scientist, Discovery Sciences, AstraZenecaAaron Morris, Ph.D., Lab Head, Cancer Biology, Sanofi OncologyMichelle Palmer, Ph.D., Director, Discovery and Preclinical Research, BroadInstituteCaroline Shamu, Ph.D., Lecturer, Systems Biology and Director, ICCB-Longwood, Harvard Medical SchoolD. Lansing Taylor, Ph.D., Director, University of Pittsburgh Drug DiscoveryInstitute and Allegheny Foundation; Professor, Computational and SystemsBiology, University of Pittsburgh*Separate registration requiredWednesday, October 307:30 am Breakfast Presentation (Sponsorship Opportunity Available)or Morning CoffeeFunctional Analysis andTargetID/Validation with 3-D Models8:25 Chairperson’s Opening Remarks8:30 Functional Analysis ofTherapeutic Antibodies Using ex vivoTumor SpheroidsMitchell Ho, Ph.D., Chief, Antibody Therapy Section, Laboratory of MolecularBiology, National Cancer Institute, NIHTumor microenvironments present significant barriers to antibody therapy.We established ex vivo tumor spheroids to study molecular mechanismsof antibody drug resistance. The tumor spheroids may prove invaluable foridentifying potential targets in addition to providing an innovative platform foranalyzing therapeutic antibodies. We compared the global gene expressionprofiles of spheroids and monolayers and identified genes specific to the3-D biological structure of mesothelioma. An update on generation of humansingle-domain antibodies for cancer therapy will also be discussed.8:55Third Dimension:The Future of RNAi-DrivenTargetIdentification in CancerGeoffrey A. Bartholomeusz, Ph.D., Assistant Professor and Director, siRNACore Facility, Department of Experimental Therapeutics, Division of CancerMedicine, University of Texas MD Anderson Cancer Center3-D spheroid cell cultures, unlike 2-D monolayer cell cultures, demonstrateproperties that are highly co-related to tumors. The ease at which spheroidmodels can be applied in high-throughput screens has resulted in therealization of their importance to address relevant questions in tumorbiology. We are developing 3-D spheroid cell culture models to be used inhigh-throughput screening, and the design of one such model for targetidentification utilizing high-throughput RNAi screens will be discussed.9:20 Identification ofTherapeuticTargets in 3-Dimensional Patient-DerivedTumor Spheroids with Cancer Stem Cell CharacteristicsFredika M. Robertson, Ph.D., Professor, Experimental Therapeutics, Center forTargeted Therapy; Director, Translational Therapeutics Laboratory, University ofTexas MD Anderson Cancer CenterTumor cells isolated from breast cancer patients with metastatic diseasemanifested by pleural effusion spontaneously form 3-D tumor aggregatesthat retain characteristics of tumor initiating cells/cancer stem cells. Thispresentation will discuss the use of a combination of analytical platformsincluding high-content live-cell imaging, confocal microscopy, flow cytometry,and histological approaches for phenotypic analysis of tumor spheroidsthat serve as surrogates of metastasis. These approaches provide us withpowerful tools to identify those patients who may benefit from inclusioninto clinical trials for new therapeutics under development. The use of theseapproaches to identify specific signaling pathways and molecular drivers ofdisease progression will also be discussed.9:45 A 3-D Culture-Based siRNA ScreeningTool for SecretoryEpithelium CancerTargetsNathalie Picollet-D’Hahan, Ph.D., Senior Researcher, iRTSV/Biomics, CEAGenetic screening is certainly one of the most powerful approaches to gaininsights into gene function and complex biological processes. However, it isbecoming evident that functional genomics screens need to be performedin a more physiologically-relevant environment provided by a 3-D context.We propose to combine two technological innovations; both in microfluidic-generated 3-D cultures and parallelized lens-less imaging to perform 3-DRNAi-based HTS and to characterize new biomarkers in prostate cancer. Weemployed silencing RNAs (siRNA), targeting kinase-related genes to identify3-D-specific effectors of prostate acini morphogenesis and polarity.10:10 Sponsored Presentation (Opportunity Available. Contact IlanaQuigley at 781-972-5457 or iquigley@healthtech.com.)10:25 Coffee Break in the Exhibit Hall with Poster ViewingComplex Models ofTumor Microenvironment11:15 Engineering 3-D in vitroTumor Models of AntineoplasticDrug Resistance: Use of Malignant Spheroids andNon-Malignant Accessory Cells from the MetastaticMicroenvironmentEugen Dhimolea, Ph.D., Research Fellow, Medical Oncology, Dana FarberCancer Institute, Harvard Medical SchoolTo model the composition and architecture of metastatic lesions and toaddress the role of the local metastatic microenvironment in the drugresistance exhibited by disseminated cancers, we assembled heterotypic invitro 3-D tissue cultures comprised of malignant cells growing in dispersedformat vs. growing as spheroids; and in the presence vs. absence of non-malignant accessory cells from organs frequently targeted by metastaticdisease. We assessed the pathophysiological relevance of these models bytesting the activity of more than 100 FDA-approved antineoplastic drugs. Thespheroid morphology significantly decreased the efficacy for several classesof conventional DNA-damaging (e.g. anthracyclins) agents as well as recentlyestablished targeted therapies (e.g. kinase inhibitors), while being associatedwith increased cell-killing activity of others. Our 3-D co-culture systemprovides a practical and clinically-relevant experimental system to study themechanisms of metastatic microenvironment-related drug resistance and toscreen for biologically active compounds that circumvent it.11:40Tumor-Microenvironment-on-Chip (TMOC)Bumsoo Han, Ph.D., Associate Professor, Mechanical and BiomedicalEngineering, Purdue UniversityTargeted delivery of therapeutic and imaging agents to tumors withoutnon-specific accumulation at normal tissues can significantly improve thetreatment and diagnosis of cancers. Nanotechnology recently enabledvarious functional nanoparticles as vehicles for targeted delivery. However,it is extremely challenging to optimize their design and configuration usingtraditional cell culture and animal models. In order to address this challenge,a new in vitro model was developed to simulate the complex 3-D tumormicroenvironments relevant to the transport of nanoparticles.12:05 pmThree-Dimensional Melanoma Models: From Screeningto Skin ReconstructsAdina Vultur, Ph.D., Staff Scientist, Wistar InstituteThe melanoma field has seen unprecedented clinical successes in thelast few years; however, tumor heterogeneity and plasticity indicate therequirement for an arsenal of therapeutic strategies to overcome advanceddisease. We focus our efforts on investigating genetically-distinct melanomasubgroups using high-throughput 3-D screening assays (with and withouta support matrix) and increasingly complex preclinical models from normalhuman skin reconstructs to patient-derived xenografts. Our melanoma modelpipeline has already allowed us to identify compounds and targets withlimited activity in the 2-D setting, but with potential in vivo.12:30 Close of Physiologically-Relevant CellularTumor Models forDrug Discovery Meeting
  12. 12. Additional registration detailsEach registration includes all conferencesessions, posters and exhibits, foodfunctions, and access to the conferenceproceedings link.Handicapped Equal Access: In accordancewith the ADA, Cambridge HealthtechInstitute is pleased to arrange specialaccommodations for attendees withspecial needs. All requests for suchassistance must be submitted in writingto CHI at least 30 days prior to the startof the meeting.To view our Substitutions/Cancellations Policy, go tohttp://www.healthtech.com/regdetailsVideo and or audio recording of any kindis prohibited onsite at all CHI events.Receive a FREE eNewsletter by signing upat chimediagroup.comThe latest industry news, commentary and highlights from Bio-IT WorldInnovative management in clinical trialsA series of diverse reports designed tokeep life science professionals informedof the salient trends in pharmaceuticaltechnology, business, clinical development,and therapeutic disease markets.For a detailed list of reports, visitInsightPharmaReports.com, or contactRose LaRaia, rlaraia@healthtech.com,+1-781-972-5444.Barnett is a recognized leader in clinicaleducation, training, and reference guidesfor life science professionals involved inthe drug development process. For moreinformation, visit barnettinternational.com.Cambridge Healthtech Associates™(CHA™) leverages its extensive networkand unique collaborative model inconsulting, technology evaluationsand community-based communicationservices to help clients in the lifesciences industry commercialize andpenetrate the marketplace to increaserevenue. Visit www.chacorporate.com.Pricing and Registration InformationMULTIPLE CONFERENCE PRICING – Best VaLue! Academic, Government,(Includes access to 2 conferences, excludes short courses) Commercial Hospital-affiliatedEarly Registration Discount until August 2, 2013 $2199 $1099Advance Registration Discount until September 20, 2013 $2399 $1199Registrations after September 20, 2013 and on-site $2599 $1299SINGLE CONFERENCE PRICING(Includes access to 1 conference, excludes short courses)Early Registration Discount until August 2, 2013 $1399 $649Advance Registration Discount until September 20, 2013 $1599 $729Registrations after September 20, 2013 and on-site $1799 $799Monday, October 28 - Tuesday, October 29 Tuesday, October 29 - Wednesday, October 30Engineering Functional 3-D Tissue Models Screening and Functional Analysis of 3-D Models Phenotypic Drug Discovery Physiologically-Relevant Cellular Tumor Models for Drug DiscoverySHORT COURSE PRICING(Includes access to short courses only)Single Short Course $595 $295Two Short Courses $895 $495Three Short Courses $1095 $595Sunday, October 27 SC1: Scaffolds: Bridging the Gap Between2-D and 3-DMonday, October 28 SC3: Introduction to High-ContentPhenotypic ScreeningMonday, October 28 SC2: Automating a 3-D Culture ScreeningLaboratory: Meeting the ChallengesTuesday, October 29 SC4: Expert ThinkTank: How to Meet theNeed for Physiologically-Relevant Assays?Conference DiscountsDrug Safety Executive Council (DSEC)- Discount ($50 off)Members of the DSEC community will receive a $50 discount off the conference registration. Our records must indicate you are a member.NGS Leaders- Discount ($50 off)Members of the NGS Leaders community will receive a $50 discount off the conference registration. Our records must indicate you are a member.Poster Submission- Discount ($50 off)Poster abstracts are due by September 27, 2013. Once your registration has been fully processed, we will send an email containing a uniquelink allowing you to submit your poster abstract. If you do not receive your link within 5 business days, please contact jring@healthtech.com. *CHI reserves the right to publish your poster title and abstract in various marketing materials and products.REGISTER 3 ­- 4th IS FREE: Individuals must register for the same conference or conference combination and submit completed registration form togetherfor discount to apply.Additional discounts are available for multiple attendees from the same organization. For more information on group rates contactDavid Cunningham at +1-781-972-5472If you are unable to attend but would like to purchase the Functional Analysis & Screening Technologies Congress CD for $750 (plus shipping), please visit FASTCongress.com. Massachusetts delivery will include sales tax.How to Register: FASTCongress.comreg@healthtech.com • P: 781.972.5400 or Toll-free in the U.S. 888.999.6288Please use keycodeSCN Fwhen registering!Cambridge Healthtech Institute250 First Avenue, Suite 300, Needham, MA 02494www.healthtech.com  •  Fax: 781-972-5425

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