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High-content analysis (HCA) provides the ability to study many cellular features simultaneously and has the power to revolutionize drug discovery, especially as it is applied to more physiologically relevant models. Complex biological pathways may be explored, drug efficacy predicted, and ultimately, attrition rate reduced; however, challenges remain as these complex assays push the field forward. Cambridge Healthtech Institute’s High-Content Analysis conference will cover applications of HCA in preclinical drug discovery, challenges of the high-content screening environment, and HCS in immuno-oncology.


Final Agenda

Wednesday, June 20

11:00 am Registration Open (America Foyer)

11:45 Enjoy Lunch on Your Own

12:20 pm Dessert and Coffee Break in the Exhibit Hall with Poster Viewing (America Ballroom)


1:00 PLENARY KEYNOTE SESSION
Essex South

2:30 Refreshment Break in the Exhibit Hall with Poster Viewing (America Ballroom)

PHENOTYPIC DRUG DISCOVERY APPROACHES
Essex North East

3:10 Chairperson’s Opening Remarks

Regis Doyonnas, PhD, Senior Principal Scientist, Primary Pharmacology Group, High Content Screening Lead, Worldwide R&D, Pfizer

3:15 The Phenomics Discovery Initiative (PDi): Recruiting and Translating Academic Disease-Predictive Biology into the Pharma Drug Discovery Pipeline

Denise_BarraultDenise Barrault, PhD, Executive Director, National Phenotypic Screening Centre

Academic and clinical communities carry out vast amounts of novel biological research, which is underexploited and lacks the rigour and purpose for effective translation. At the National Phenotypic Screening Centre (NPSC) we have formed a public-private consortium called the Phenomics Discovery Initiative (PDi) that allows the pre-competitive de-risking of phenotypic assays for development, screening and validation. PDi leverages NPSC’s world class facilities, industry standard operation and extensive global networks to crowdsource and develop the best biology.

3:45 Image and Flow Cytometry-Based High-Content Phenotypic Screenings in Drug Discovery

Regis_DoyonnasRegis Doyonnas, PhD, Senior Principal Scientist, Primary Pharmacology Group, High Content Screening Lead, Worldwide R&D, Pfizer

High disease relevance in cell-based assays is one of the most important goals in phenotypic assay development. Opportunities and challenges to combine patient-derived, disease-specific cells with high-content screening technologies with the aim of finding new targets and new drugs will be discussed during this presentation. 

4:15 Phenotypic Screening of Small Molecule Enhancers of Basal Autophagy: HCS and New Informatics Tools

Rafael_FernandezRafael Fernandez, PhD, Principal Scientist, Pharmacology, Merck Research Laboratories

An annotated collection of 6,000 tool compounds was used in a pilot screen to identify inducers of basal cellular autophagy. Using a frozen-in-time, high-content imaging approach to identify autophagosomes, multiple hit classes were identified based on mono- and multi-parametric and machine learning data analytics.

 

 4:45 Agnostic Approaches for Drug Discovery

Thierry_DorvalThierry Dorval, PhD, HCS Group Leader, Institut de Recherches Servier

High-content screening provides an extremely powerful way to multiplex readouts from biological experiments in a high throughput way, generating statistically robust results. Screening and assay development could benefit from this approach to have better understanding of the biology and a more robust characterization of the selected hits during screening campaign. However, there is a need for adapted tools to visualize and automatically support decision. The presentation will cover what we have developed to address this aspect at Servier’s group

5:15 Q&A with the Speakers

5:45 Close of Day and Dinner Short Course Registration*

*Separate registration required.

Thursday, June 21

7:30 am Registration Open (America Foyer) and Morning Coffee (Foyer)

SCREENING OF IPSC-DERIVED NEURONS
Essex North East

8:00 Chairperson’s Remarks

Christopher Untucht, PhD, Senior Scientist, Head of Cell Imaging Platform, Neuroscience Discovery Core Technologies, AbbVie Deutschland GmbH & Co. KG

8:05 HCS Neurite Outgrowth Assay Using iPSC-Derived Neurons

Christopher_UntuchtChristopher Untucht, PhD, Senior Scientist, Head of Cell Imaging Platform, Neuroscience Discovery Core Technologies, AbbVie Deutschland GmbH & Co. KG

Human induced pluripotent stem cell (hiPSC) derived neuronal cells are a promising source to fill the unmet need for human cells in preclinical drug discovery. Screening for compounds that affect growth and function of neurites is of particular interest for the discovery of treatment opportunities in the area of neurodegenerative diseases such as Alzheimer’s Disease (AD) and Multiple Sclerosis (MS). Neurite outgrowth displays a scalable and quantifiable mechanism demonstrating the dynamic response of neurons to effectors from the environment.

8:35 Phenotypic Screening of hiPSC-Derived Neuronal Networks Using Multielectrode Arrays

Deborah_PreDeborah Pre, PhD, Scientist, Conrad Prebys Center for Chemical Genomics, Sanford Burnham Prebys Medical Discovery Institute

Neurological disease modeling and drug discovery efforts would greatly benefit from human cell-based platforms to study neuronal networks and synaptic plasticity. Using human induced pluripotent stem cell (hiPSC)-derived neurons, we have developed a multielectrode array (MEA) assay in multi-well formats that recapitulates physiologically relevant synchronized bursting properties sensitive to shifts in excitation/inhibition balance. We will discuss use of this assay for compound screening and modeling of synaptic plasticity.

9:05 Q&A with the Speakers 

9:35 Find Your Table and Meet Your Moderator

9:40 Interactive Breakout Discussion Groups

This session features various discussion groups that are led by a moderator/s who ensures focused conversations around the key issues listed. Attendees choose to join a specific group and the small, informal setting facilitates sharing of ideas and active networking.

How to Design Machine Learning Models to Automatically Identify Biological Mechanisms

Greg Johnson, PhD, Scientist & Machine Learning Specialist, Allen Institute for Cell Science

  • Data representation
  • Model architecture
  • Designing an objective function

Challenges in Phenotypic, Target Agnostic Drug Discovery

Jesus Medina, PhD, Manager, Medicinal Chemistry, GlaxoSmithKline

  • Key challenges in cell-based phenotypic drug discovery efforts
  • Early assessment of the validity and viability of hits obtained from screens
  • What aspects of phenotypic drug discovery are the most advantages in drug discovery

10:20 Coffee Break in the Exhibit Hall with Poster Viewing (America Ballroom)

HIGH-CONTENT SCREENING IN IMMUNO-ONCOLOGY AND BIOLOGICS DRUG DISCOVERY & DEVELOPMENT
Essex North East

11:00 Chairperson's Remarks

Shane Horman, PhD, Research Investigator III, Genomic Institute of the Novartis Research Foundation

11:05 An Ultra HTS 3D Assay Platform for Enhancing T-Cell-Mediated Tumor Killing

Shane_HormanShane Horman, PhD, Research Investigator III, Genomic Institute of the Novartis Research Foundation

Overcoming tumor-mediated immunosuppression and enhancing cytotoxic T-cell activity within the tumor microenvironment are two central goals of immuno-oncology (IO) drug discovery initiatives. However, exploratory assays involving immune components are often plagued by low-throughput and poor clinical relevance. Here we present a novel ultra-high-content assay platform for interrogating T-cell-mediated killing of 3D tumor spheroids that yields multi-parametric, clinically-relevant data and can be employed kinetically for the discovery of novel IO therapeutic agents.

11:35 Image-Based Antibody Internalization Assays in Biologics Drug Development

Joern_HopkeJoern Hopke, PhD, Senior Research Investigator, Sanofi Biologics Research

In recent years, pharmaceutical drug discovery has increasingly focused on biologics and therapeutic antibodies in particular. Biologics research and development depend on the functional and mechanistic characterization of those antibodies. Their cellular internalization is a key feature that needs to be empirically determined, as it is either a desired or unwanted attribute, depending on the required mode of action. Utilizing high content imaging instrumentation and analysis, we have adopted a wide variety of strategies to interrogate antibody internalization.

12:05 pm High-Content Imaging to Enable Biologics Drug Discovery

Lorraine_IrvingLorraine Irving, PhD, Research Scientist, MedImmune

Biologic drugs, which include monoclonal antibodies, recognise their target molecules with high specificity. To facilitate the identification of new biologic candidate drugs at Medimmune, functional high content imaging (HCI) assays are being applied throughout the biologics drug discovery process. Disease relevant HCI assays enable new target identification, functional lead selection, mechanistic studies and affinity/dose modelling predictions. PerkinElmer Opera and Molecular Devices Image Xpress Micro HCI systems are routinely used.

 

12:35 Networking Luncheon in the Exhibit Hall with Poster Viewing (America Ballroom)

ORGANOID-BASED HIGH-CONTENT SCREENING
Essex North East

1:55 Chairperson’s Remarks

Shay Soker, PhD, Professor, Institute for Regenerative Medicine, Wake Forest School of Medicine

2:00 Tumor Organoids and Patient-Derived Tumor Organoids for Drug Discovery and Personalized Medicine in Gastrointestinal Cancer

Daniel_LaBarberaDaniel V. LaBarbera, PhD, Associate Professor, Drug Discovery and Medicinal Chemistry; Director, High-Throughput Screening and Chemical Biology Core Facility, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado


2:30 Multi-Tissue Interactions in an Integrated Three-Tissue Organ-on-a-Chip Platform

Shay_SokerShay Soker, PhD, Professor, Institute for Regenerative Medicine, Wake Forest School of Medicine

Organoid and organ-on-a-chip technologies are rapidly advancing towards deployment for drug and toxicology screening applications. Few engineered model systems, including the growing variety of organoid and organ-on-a-chip platforms, have so far reflected the interactive nature of the human body. To address this challenge, we have developed an assortment of bioengineered tissue organoids and tissue constructs that are integrated in a closed circulatory perfusion system, facilitating inter-organ responses. We describe a multi organ-on-a-chip system.

COMPLEX CELLULAR MODELING WITH HIGH-CONTENT ANALYSIS
Essex North East

3:00 Machine Learning of the Assembly Instructions of a Cell

Timothy Majarian, Associate Computational Biologist, Broad Institute of MIT

An important challenge enabled by the growth in microscope technologies is to be able to combine information from diverse images into comprehensive models of cell organization, rather than to just describe or compare images. Methods have been described for creating generative models of cells, and recent progress has been made on a critical remaining challenge: learning how the spatiotemporal distribution of each component depends upon those of other components.

3:30 The Allen Institute for Cell Science: Building an Integrated Cell

Greg_JohnsonGreg Johnson, PhD, Scientist & Machine Learning Specialist, Allen Institute for Cell Science

Understanding the organization of the cell is an underlying goal of the Allen Institute for Cell Science. Here, we present two conditional models of subcellular localization that allow for the prediction of unobserved structures, learned directly from fluorescence images. We demonstrate our models generalize to a wide range of subcellular localization patterns and allow for a probabilistic interpretation of this organization. This project forms the foundation for further work the prediction of cell organization and behaviors.

4:00 Close of Conference