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Functional Genomics Screening Strategies

 

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Cambridge Healthtech Institute’s 10th annual conference will cover the latest in the use of chemical genomics tools, cDNA overexpression assays and the potential use of micro RNA (miRNA) and long non-coding RNAs for identifying and validating drug targets, exploring unknown cellular pathways, and for performing translational studies such as, biomarker discovery, drug modifier screens and more.

TUESDAY, OCTOBER 2


Exploring Diverse Applications

1:30 pm Chairperson’s Remarks

Scott Martin, Ph.D., Team Leader, RNAi Screening, NIH Chemical Genomics Center

1:40 Synergistic Application of RNAi Screening, Next-Generation Sequencing and Expression Profiling to Biomarker Discovery

Namjin Chung, Ph.D., Senior Research Investigator, Applied Genomics, Bristol-Myers Squibb Co.

Discovery of genomic biomarkers has been driven largely by expression profiling of responder and non-responder patients. While this has proven a powerful approach, it often requires a large number of clinical samples, which can be costly and time consuming. Recent advances in RNAi screening and next-gen sequencing technologies enable a synergistic application of the three genomics technologies to the discovery of predictive biomarkers. By illustrating a recent oncology project at BMS, I will demonstrate the concept and feasibility of this approach, and how it can compliment conventional expression profiling approaches.

2:10 A Global RNAi Screen Identifies Novel Chemosensitizer and Chemoresistant Oncology Targets Leading to Combination Therapies and Markers of Drug Resistance

Attila Seyhan, Ph.D., Senior Biomarker Discovery and Development Leader, formerly at Translational Immunology, Biotherapeutics Clinical R&D, Pfizer, Inc.

We undertook a genome-wide pooled lentiviral shRNA screen to identify novel targets with neratinib, a tyrosine kinase inhibitor of the ErbB receptor family, currently in Phase III trials. We discovered novel genes and pathways whose inhibition selectively impaired or enhanced the viability of cancer cells in the presence of sub-effective or lethal concentrations of neratinib. This led to the development of combination paclitaxel or cytarabine treatments and potential patient selection genetic biomarkers.

2:40 A Genome-Wide Screen for Novel Genes Involved in Sensitisation to Histone Deacetylase Inhibitors

Kaylene Simpson, Ph.D., Head, Victorian Centre for Functional Genomics, Cancer Genetics, Peter MacCallum Cancer Centre, Australia

The pan histone deacetylase inhibitor (HDACi), vorinostat, has achieved remarkable clinical success but certain patients remain unresponsive. We have screened genome-wide protein coding and miRNA targets to elucidate vorinostat resistance mechanisms to identify novel genes that sensitize cells to vorinostat-induced apoptosis.

3:10 Refreshment Break in the Exhibit Hall with Poster Viewing

3:45 Genomic Platforms to Generate Unbiased Responder and Treatment Hypotheses for Oncology Translational Research

Jing Li, Ph.D., Director of Genomics Screening, Discovery and Pre-clinical Science, Merck Research Laboratories

It is becoming clear that, to be successful, cancer treatments must be tailored to individual patients based on specific genetic drivers of tumor growth. Several pre-clinical platforms, including synthetic lethal screens (SLS) and matrixed compound screen in large panel of cancer cell lines are designed to address these specific issues. This presentation will discuss how these platforms are complementary to each other and how they facilitate oncology translational research by generating treatment and responder hypotheses.

ACellecta4:15 Discovery of Cancer Drug Targets Using RNAi Screening with Pooled Lentiviral shRNA Libraries

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

Phenotypic loss-of-function RNAi screens with complex lentiviral-based shRNA expression libraries enables simultaneous screening of several thousand target genes to identify those that regulate specific cellular responses and often indicate new therapeutic targets. Properly constructed pooled shRNA libraries with constrained hairpin representation optimized for HT sequencing produce robust results. The presentation will show examples of screens from in vitro and in vivo models using both “drop-out” viability and positive “rescue” selections.

4:45 Comprehensive Analysis of Host Factors Modulating HIV-1 Replication Using Multiple RNAi Libraries

Abraham Brass, M.D., Ph.D., Assistant Professor, Department of Microbiology and Physiology Systems, University of Massachusetts Medical School

To produce an integrated map of HIV-host interactions we screened multiple RNAi libraries using a HeLa-cell based high-content imaging platform. This effort confirmed and extended previous screening efforts by demonstrating the essential roles of the mediator complex, nuclear pore complex, and the conserved-oligomeric-Golgi complex, in HIV infection. We also newly identified the THO complex (THOC), which couples transcription to mRNA export, as being required for HIV replication. Different THOC components scored across multiple screens, revealing the presence of false negatives and the value of large scale integrated genetic efforts. This strategy represents a useful approach towards identifying candidate genes by overcoming some of the hurdles confronting functional genomics.

Cyto Pathfinder5:15 siRNA Screening using Solid Phase Transfection

Alun McCarthy, Ph.D., CSO, CytoPathfinder Inc.
CytoPathfinder’s proprietary accelerators significantly enhance solid-phase transfection. This technology allows efficient and cost-effective siRNA screening, and facilitates studies difficult to carry out by other methods, such as knockdowns in hard-to-transfect cells (e.g. primary neurons) and double knockdowns.  miRNA and iPS cell applications are being developed.

5:30 End of Day



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PREMIER SPONSOR 

Cellecta 

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SPONSORSHIPS & EXHIBITS 

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
781-972-5483
jstroup@healthtech.com 

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