Part A: RNAi for Functional Genomics Screening Conference header

About This Conference:

Cambridge Healthtech Institute’s eleventh annual conference on RNAi for Functional Genomics Screening will cover the latest in the use of RNA interference (RNAi) screens for identifying and validating new drug targets and exploring unknown cellular pathways. It will cover everything from assay design to data analysis for the use of in vitro and in vivo siRNA (small interfering RNA) and shRNA (short hairpin RNA) screens, in a way that will evoke thought-provoking discussions and inspire collaborations.

Wednesday, October 8

7:00 am Registration and Morning Coffee


8:05 Chairperson’s Opening Remarks

8:15 FEATURED PRESENTATION: Functional RNAi Screens for Cancer in Mice

ElaineFuchsElaine Fuchs, Ph.D., Rebecca C. Lancefield Professor and Investigator, Howard Hughes Medical Institute, Laboratory of Mammalian Cell Biology and Development, The Rockefeller University

Using mouse as a model, Fuchs’ team has made major contributions towards understanding how tissues repair injuries and how abnormalities in stem cell behavior can lead to cancers. Recently, her team developed technology to conduct genome-wide RNAi screens in mice for oncogenic regulators of growth. She’ll discuss the methodology, findings and implications for sifting through the functional significance of hundreds of gene mutations found in human epithelial cancers.

9:00 In vivo Synthetic Lethality Screens to Identify Genetic Dependencies in Patient-Derived Tumor Models

Timothy Heffernan, Ph.D., Senior Associate Director, Target Discovery and Deputy Head, Center for Co-Clinical Trials, Institute for Applied Cancer Science, University of Texas, MD Anderson Cancer Center

Large scale sequencing has uncovered a staggering level of complexity of cancer genomes and made clear that translation of genomic knowledge into effective therapeutics will require systematic approaches to inform on context-specific genetic dependencies. We describe an in vivo synthetic lethality platform that leverages deep coverage shRNA libraries to interrogate genetic dependencies in patient-derived tumor models. We report how this platform has informed novel targets and strategies to overcome drug resistance.

9:30 Applying Pooled RNAi Screens in CD8 T Cells During Viral Infections in Mice

Matthew Pipkin, Ph.D., Assistant Professor, Department of Cancer Biology, Florida Campus, The Scripps Research Institute

Naïve CD8 T cells differentiate into cytotoxic T lymphocytes (CTL) that lyse infected or malignant host cells. Most CD8 T cell-intrinsic factors that regulate this process are unknown. I will present an approach to conduct pooled RNAi screens in antigen-specific CD8 T cells using shRNAmirs in the context of viral infections in mice, as well as identification and validation of some novel players that underlie generation of protective CTL, and mechanistic insight into their function(s).

10:00 Grand Opening Coffee Break in the Exhibit Hall with Poster Viewing


10:45 In vivo Target Validation with Viral Vectors: Translating in vitro Hits to in vivo Functions

Ki Jeong Lee, Ph.D., Principal Scientist, Genome Analysis Unit, Amgen, Inc.

We investigated the in vivo biological roles of cDNAs that were identified through in vitro functional genomic screens or based on expression patterns related to disease states. Recombinant adeno-associated virus (rAAV) was utilized for in vivo gene expression, partly because of its ability to confer long-term gene expression with a single injection. This strategy was also used to further validate hits from in vitro screens and to identify novel drug targets based on in vivo phenotypes.

11:15 Cell-based Screening to Empower Human Genetics: Moving From Gene to Genetic Variant

Heiko Runz, M.D., Director, Human Genetics, Merck Research Laboratories

Sequencing technologies identify a number of potentially disease-relevant variants in the human genome, but our abilities to accurately evaluate which of these variants are of the highest relevance to human health and disease are lagging behind. I will demonstrate how systematic strategies to profile the biological effects of genetic variants by RNAi and cDNA-overexpression in cells can help us to prioritize genetic factors that control blood cholesterol levels and the risk for early-onset risk for early-onset myocardial infarction.

11:45 RNAi Screens for Identification of Rare Genetic Disease Treatments

Chris Gibson, Ph.D., CEO, Recursion Pharmaceuticals

Orphan diseases are increasingly targets of interest for both large and small pharmaceutical companies. A large proportion of orphan diseases are due to loss-of function genetic mutations. As such, RNAi presents an opportunity and a challenge in terms of efficiently modeling a large number of these diseases. A variety of strategies for modeling genetic diseases using RNAi in human cells will be discussed, including highlights of the many challenges associated with working in this space.

Charles River(1)12:15 pm Identification of Novel Anti-Obesity Genes in Primary Human Adipocytes using RNAi Screening

David Fischer, Ph.D., Senior Director, Biological Sciences, BioFocus, a Charles River Company

We sought to identify novel genes implicated in adipose fat reduction by affecting triglyceride hydrolysis and/or increasing the metabolic capacity of the adipocytes. These gene products directly or components in the signaling pathway(s) of these gene products can be used as drug targets for the development of novel targeted anti-obesity therapies. 

12:30 Sponsored Presentation (Opportunity Available)

12:45 Session Break

Sigma_NEW1:00 Luncheon Presentation - The State of CRISPR Technology

Shawn Shafer, Ph.D., Functional Genomics Market Segment Manager, Sigma-Aldrich Emerging Technologies

Since it’s elucidation a mere two years ago, applications for the CRISPR pathway have expanded broadly and rapidly. In this talk, we will review the current state of the technology and look at how CRISPR is being applied to the fields of genome editing, screening, and gene regulation, among other topics.

1:40 Session Break


1:50 Chairperson’s Opening Remarks

Geoffrey A. Bartholomeusz, Ph.D., Assistant Professor and Director, siRNA Core Facility, Department of Experimental Therapeutics, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center

2:00 Relevance of 3D Cell Culture Models and siRNA Screens for Target Identification and Drug Development

Geoffrey A. Bartholomeusz, Ph.D., Assistant Professor and Director, siRNA Core Facility, Department of Experimental Therapeutics, Division of Cancer Medicine, The University of Texas, MD Anderson Cancer Center

3D cell culture models are varied and complex and unlike 2D monolayer cell cultures, replicate certain biological outcomes observed in a tumor microenvironment. The reliability of data generated from 3D cell culture-based studies is dependent on the development of appropriate model. The development of 3D models used in high-throughput screening to address relevant questions in cancer biology will be discussed.

2:30 RNAi Off-Target Effects - Can They Be Used to Our Advantage?

Christian von Mering, Ph.D., Chair, Computational Biology, Institute of Molecular Life Sciences, University of Zurich and Swiss Institute of Bioinformatics

A comparative analysis of several genome-wide RNAi screens has been performed. This enabled the relative quantification of on-target and off-target effects, considering real-life phenotypes in a high-throughput setting. In all cases, the average phenotypic consequence of a given RNAi oligo is dominated by the off-target mechanism, with on-target signals low or completely absent. However, custom-designed oligos focusing exclusively on the off-target mechanism may become promising perturbation reagents, targeting entire pathways instead of single genes.

3:00 Loss-of-Function Genetic Screens to Find Genes Regulating Cell Responses and Identify Potential Drug Targets

Paul Diehl, Ph.D., Director, Commercial Development, Cellecta, Inc.

RNAi-based loss-of-function genetic screens using pooled shRNA libraries have proven to be an efficient way to identify genes responsible for a range of cell responses. However, generating robust results with this technique requires viral-based shRNA libraries with constrained hairpin representation and sequence-optimized barcodes. This presentation will discuss enhancements in genetic screens that enable tracking of distinct clonal cell populations in pooled screens, dropout viability screening in xenograft tumor models, and complementary CRISPR-based approaches to genetic screens.

3:30 Refreshment Break in the Exhibit Hall with Poster Viewing

4:10 Integrating High-Throughput Imaging and Genomics to Identify Drug Combinations in Cancer

Arvind Rao, Ph.D., Assistant Professor, Department of Bioinformatics and Computational Biology, The University of Texas, MD Anderson Cancer Center

High-throughput screening is routinely used to identify the role of RNAi in modulating cellular phenotype as well as to study the effects of therapeutics on diseased cell morphology. A high-throughput kinome siRNA screen was carried out to study their effects on tumor architecture in 3D tumor spheroids. We present a workflow to identify and interpret gene function in such large scale 3D RNAi experiments by analyzing such image-derived data in the context of associated molecular data.

4:40 CARD: A Platform for Comprehensive and Integrative Analysis of RNAi Screen Data

Bhaskar Dutta, Ph.D., Staff Scientist, Laboratory of Systems Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health

Although RNAi screen is widely used, there is no user-friendly application for comprehensive analysis and interpretation of the data. We have developed a web-based application that integrates different existing and novel algorithms associated with screen data analysis, e.g., different normalizations, transformations, common seed analysis, expression filter, RNAiCut, pathway enrichment, network analysis, etc.

5:10 Interactive Breakout Discussion Groups

This interactive session provides conference delegates and speakers an opportunity to choose a specific roundtable discussion group to join. Each group has a moderator to ensure focused discussions around key issues within the topic. This format allows participants to meet potential collaborators, share examples from their work, vet ideas with peers, and be part of a group problem-solving endeavor. The discussions provide an informal exchange of ideas and are not meant to be a corporate or specific product discussion.

Assay Design Considerations for RNAi Screens

Caroline Shamu, Ph.D., Director, ICCB-Longwood Screening Facility, Harvard Medical School
Scott Martin, Ph.D., Team Leader, RNAi Screening, NIH Chemical Genomics Center, National Center for Advancing Translational Sciences, National Institutes for Health

  • Key decision points in assay development for high throughput siRNA screen
  • Evaluating reagents, libraries and assay platforms
  • Recommended strategies for follow-up and validating RNAi on-target performance

Optimizing Data Analysis and Interpretation

Eugen Buehler, Ph.D., Group Leader, Informatics, National Center for Advancing Translational Sciences, National Institutes of Health
Christian von Mering, Ph.D., Chair, Computational Biology, Institute of Molecular Life Sciences, University of Zurich and Swiss Institute of Bioinformatics

  • Data handing tools and best practices
  • Considerations for hit prioritization and validation
  • Tackling off-target effects
  • Avoiding confounding viability and transcription effects


How to Best Utilize 3D Cell Culture-based Screens

Geoffrey A. Bartholomeusz, Ph.D., Assistant Professor and Director, siRNA Core Facility, Department of Experimental Therapeutics, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center
Arvind Rao, Ph.D., Assistant Professor, Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center

  • Design and use of 3D spheroid models 
  • Selecting appropriate 3D cell models for high throughput screening 
  • Standard operation procedures for performing HTS using 3D models 
  • The next generation 3D models using tumor biopsy samples 
  • Image analysis pipelines for 3D 
  • Managing big image data and data mining infrastructures, possibly on the cloud 
  • Integration across biological scale and with genomics data 

6:10 Welcome Reception in the Exhibit Hall with Poster Viewing

7:15 Close of Day

Thursday, October 9

7:30 am Registration and Morning Coffee


8:00 Chairperson’s Opening Remarks

Scott Martin, Ph.D., Team Leader, RNAi Screening, NIH Chemical Genomics Center, National Center for Advancing Translational Sciences, National Institutes for Health

8:10 From Superstar to Washed-Up Delinquent: Is it Time to Abandon RNAi Screening?

Scott Martin, Ph.D., Team Leader, RNAi Screening, NIH Chemical Genomics Center, National Center for Advancing Translational Sciences, National Institutes for Health

“Hits” from RNAi screens have evolved from being treated as mostly true positives to a laundry list of false positives. However, much is understood about the pitfalls of RNAi screening, and when applied with these in mind, the technology delivers. This talk will highlight some fruitful assays, illustrate how understanding the pitfalls improves outcome, and discuss leveraging other technologies to further refine results.

8:40 Multiple Genome-Wide JAK/STAT Cell-Based Screens Reveal a Core, Conserved Functional Pathway

Stephen Brown, Ph.D., Manager, RNAi Facility Screening, Department of Biomedical Science, University of Sheffield

The Sheffield RNAi Screening Facility is the UK’s National Drosophila cell-based functional genomics centre and has recently screened human siRNA libraries. This presentation will talk about the technical challenges of assay development and improvements we have implemented to our approaches. Specifically, I will focus on the JAK/STAT pathway and what impact our screening practices have had on three genome-wide JAK/STAT screens.

9:10 RNAi is Dead, Long Live RNAi: Reinventing the RNAi Screening Workflow

Samuel Hasson, Ph.D., Principal Investigator, Neuroscience, Pfizer, Inc.

As some contemplate the impending demise of RNAi with the rapid maturation of genome editing technologies, now is the time to rethink RNAi-based functional genomics. New systematic methodologies that embrace the rampant off-target effects can strengthen the utility and effectiveness of RNAi screening. By enhancing the screening workflow with seed-profiling, reagent multiplicity, c911 controls, and a genome editing-powered RNAi “breakout”, the platform can evolve in a changing landscape.

9:40 Coffee Break in the Exhibit Hall with Poster Viewing

10:30 siRNA Screening for Drug Target Identification: Synthetic Lethal Genes and Optimal Drug Combinations

Carla Grandori, M.D., Ph.D., Research Associate Member, Human Biology Division, Fred Hutchinson Cancer Research Center

To overcome the challenge of identifying cancer drug targets, in particular for undruggable oncogenes, we have employed a unique platform of high-throughput siRNA screening that combines use of isogenic cell systems, cancer cell lines and primary cancer cultures with an integrated genomic approach for hit selection. Results to validate novel targets across different cancer types will be presented suggesting that despite tissue specific programs and concurrent genetic changes, certain MYC-synthetic lethal interactions are shared among tissues.

11:00 A High-Content Screen of an Arrayed cDNA Library for Modulators of Adipogenic Differentiation

Patrick Collins, Ph.D., Senior Scientist, Genome Analysis Unit, Amgen, Inc.

We screened an arrayed cDNA library in a mouse mesenchymal stem cell line to identify proteins with an effect on adipogenesis. Images of stained cells were analyzed and dozens of features extracted. A variety of multiparametric analyses identified clones for further study by imaging and highly multiplexed gene expression analysis. The screen revealed modulators of adipogenesis, as well as a variety of phenotypes providing broader insight into mesenchymal stem cell biology.

11:30 Enjoy Lunch on Your Own

1:00 pm Plenary Keynote Program 

Chas BountraChas Bountra, Ph.D., Professor of Translational Medicine & Head, Structural Genomics Consortium, University of Oxford

Martin TolarMartin Tolar, M.D., Ph.D., Founder, President & CEO, Alzheon, Inc.

Andrew L. Hopkins, Andrew L. Hopkins, D.Phil, FRSC, FSB, Chair of Medicinal Informatics and SULSA Research Professor of Translational Biology, Division of Biological Chemistry and Drug Discovery, College of Life Sciences, University of Dundee

2:45 Refreshment Break in the Exhibit Hall with Poster Viewing

3:45 Close of Conference

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2014 Discovery on Target Brochure  

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The exhibit hall was sold out in 2013, so please contact us early to reserve your place. To customize your sponsorship or exhibit package for 2014, contact:

Jon Stroup
Business Development Manager

2014 Discovery On Target CAG 



October 8 – 9

Targeting Epigenetic Readers and
Chromatin Remodelers

Targeting the Ubiquitin Proteasome System  

Big Data Analytics and Solutions  

GPCR-Based Drug Discovery  

RNAi for Functional Genomics Screening
– Part 1

Protein-Protein Interactions as Drug Targets  

Antibodies Against Membrane Protein Targets
– Part 1

October 9 – 10

Targeting Histone Methyltransferases and Demethylases  

Screening Drug Transporter Proteins  

Maximizing Efficiency in Discovery  

GPCR-Targeted Therapeutics  

Genome Editing for Functional Genomics
Screens – Part 2

Cancer Metabolism  

Antibodies Against Membrane Protein Targets
– Part 2


October 7

Next Generation Histone Deacetylase Inhibitors  


October 7

SC1: Designing Scalable Software Systems for Big Data Analytics  

SC2: Approaches for Biologically-Relevant Chemical Diversity  

SC3: Setting Up Effective RNAi Screens: From Design to Data to Validation  

SC4: Targeting Protein-Protein Interactions  

SC5: GPCR Structure-Based Drug Discovery  

SC6: Advances in Metagenomic Drug Discovery for New Anti-Infective Agents  

SC7: Targeting of GPCRs with Monoclonal Antibodies  

SC8: A Primer to Gene Editing: Tools and Applications  

SC9: Introduction to Targeted Covalent Inhibitors  

October 9

SC10: Setting Up Effective Functional Screens Using 3D Cell Cultures  

SC11: Integration of BDDCS and Extended Clearance Principles  

SC12: Introduction to Allosteric Modulators and Biased Ligands of GPCRs  

SC13: Introduction to Drug Metabolism