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SELECTBIO Conferences Academic Screening Workshop 2013

Paul Diehl's Biography

Paul Diehl, Director of Business Development, Cellecta

Dr. Paul Diehl joined Cellecta, Inc. in July 2010 where he applies his 18 years experience in commercial biotechnology and formal background in biochemistry and molecular biology to developing and expanding the company’s commercial and collaborative partnerships and interactions. Prior to joining Cellecta, Dr. Diehl held various marketing and business development positions related to developing, launching, and supporting research focused life science products and technology at B-Bridge International, Arcturus Bioscience, Agilent Laboratories, Display Systems Biotech, and Clontech Laboratories. Dr. Diehl received his B.A. in Biology from LaSalle University in Philadelphia in 1988 and his Ph.D. in Biochemistry from Washington State University in Pullman, WA in 1993. As a graduate student he analyzed the activity of E. coli isocitrate lyase using site-directed mutagenesis.

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Moving Beyond In-vitro Models: Addressing the Challenges of Pooled RNAi Screens in Xenografts

Wednesday, 18 September 2013 at 08:30

Add to Calendar ▼2013-09-18 08:30:002013-09-18 09:30:00Europe/LondonMoving Beyond In-vitro Models: Addressing the Challenges of Pooled RNAi Screens in XenograftsAcademic Screening Workshop 2013 in Baltimore, MA, USABaltimore, MA,

To date, several groups have successfully run genome-wide in vitro RNAi screening using pooled libraries expressing a complex diversity of shRNA molecules. Integral to obtaining reliable and robust results with this technique has been the use of quantitative next generation sequencing to accurately assay hairpin representation levels in the endpoint populations of cells transduced with shRNA library. However, there are significant challenges in adapting the current pooled RNAi screening approaches to more sophisticated cell model systems, such as ex-vivo xenograft models. Our studies tracking the fates of thousands of individually barcoded implanted cells found that xenograft growth is characterized by a small subset of cancer cell sub-clones that ultimately produce the bulk of the resulting tumor mass. This phenomenon significantly impacts the ability to reliably detect shRNA-induced growth inhibition in these systems. To address this problem, we have developed a novel approach to constructing pooled shRNA libraries that enables effective viability screening in systems in which external parameters strongly influence cell growth rates, such as xenograft tumors. We will present preliminary data using this approach, as well as data from more conventional in vitro “drop-out” lethality screens, to identify genes essential for cell proliferation. The results demonstrate that complex pooled shRNA libraries offer an efficient and flexible tool for both in vitro and in vivo screens aimed at discovering potential cancer therapy targets.

Add to Calendar ▼2013-09-17 00:00:002013-09-18 00:00:00Europe/LondonAcademic Screening Workshop 2013Academic Screening Workshop 2013 in Baltimore, MA, USABaltimore, MA,