The Functional Genomics Shared Resource (FG) enables Cancer Center members to perform genetic screens in cells in a rapid and effective manner. To this end, FG has established a standard workflow that starts with a feasibility assessment, transfection optimization, assay development, pilot screens, full-scale screening, data analysis, and verification of targets identified. The initial focus of FG has been siRNA screening, and to date FG has undertaken 19 projects addressing questions ranging from basic cancer biology to activity profiling of compounds with therapeutic potential. The individually arrayed siRNA Libraries in the core include a large "human druggable" collection, with 4 individual siRNAs to 7,200 genes, a similar mouse collection, and a variety of focused siRNA libraries targeting kinases, protease, GPCRs, and a Burnham-designed 1,100 gene target "Ubiquitinome" set The latter supports the strong ubiquitin interest group in the Signal Transduction Program. Given the increasing demand and role for functional genomics approaches, after two years of development. Functional Genomics is now proposed as new Shared Resource. During the next funding period, FG plans to enhance its services repertoire to include gain-offunction screening via cDNA over-expression as well as microRNA mimic and functional inhibitor screening capabilities. The facility will also increase gene coverage with a chemically modified siRNA library against the entire human genome, and implement lentiviral-mediated screening methods to be able to address cancer-relevant cells that are difficult to transfect and are out of reach for functional genomics studies using present technology. The Functional Genomics Shared Resource leverages the remarkable resources available in the Center for Chemical Genomics (in which the Chemical Library Screening Shared Resource is located), including liquid handling, automation, multimode plate readers, and high content screening equipment and expertise. In the past year. Dr. Tariq Rana joined Burnham and he serves as the Scientific Director of the FG core. As a renowned leader in the mechanisms of RNA interference (RNAi) and in RNA biology. Dr. Rana's expertise will provide critical guidance for this new Shared Resource. Overall, $99,609 in CCSG support is requested in the first year, representing 20.3% of the total estimated annual operating budget for the Functional Genomics Shared Resource.
The loss-of-function analysis enabled by siRNA screening in Functional Genomics provides an important tool in the mechanistic understanding of gene products that contribute to normal and aberrant cell growth, as well as genes and pathways that modify the response (or resistance) of tumor cells to therapeutic agents. Future gain-of-function studies with cDNA overexpression will complement these results.
|Gong, Xiao-Min; Ding, Yi; Yu, Jinghua et al. (2015) Structure of the Na,K-ATPase regulatory protein FXYD2b in micelles: implications for membrane-water interfacial arginines. Biochim Biophys Acta 1848:299-306|
|Brun, S N; Markant, S L; Esparza, L A et al. (2015) Survivin as a therapeutic target in Sonic hedgehog-driven medulloblastoma. Oncogene 34:3770-9|
|You, Weon-Kyoo; Yotsumoto, Fusanori; Sakimura, Kenji et al. (2014) NG2 proteoglycan promotes tumor vascularization via integrin-dependent effects on pericyte function. Angiogenesis 17:61-76|
|Vargas, Lina M; Leal, Nancy; Estrada, Lisbell D et al. (2014) EphA4 activation of c-Abl mediates synaptic loss and LTP blockade caused by amyloid-? oligomers. PLoS One 9:e92309|
|Volkmann, Niels; Page, Christopher; Li, Rong et al. (2014) Three-dimensional reconstructions of actin filaments capped by Arp2/3 complex. Eur J Cell Biol 93:179-83|
|Bailey, Ann M; Zhan, Le; Maru, Dipen et al. (2014) FXR silencing in human colon cancer by DNA methylation and KRAS signaling. Am J Physiol Gastrointest Liver Physiol 306:G48-58|
|Valencia, Tania; Kim, Ji Young; Abu-Baker, Shadi et al. (2014) Metabolic reprogramming of stromal fibroblasts through p62-mTORC1 signaling promotes inflammation and tumorigenesis. Cancer Cell 26:121-35|
|Northcott, Paul A; Lee, Catherine; Zichner, Thomas et al. (2014) Enhancer hijacking activates GFI1 family oncogenes in medulloblastoma. Nature 511:428-34|
|Kim, H; Claps, G; Moller, A et al. (2014) Siah2 regulates tight junction integrity and cell polarity through control of ASPP2 stability. Oncogene 33:2004-10|
|Finlay, Darren; Vamos, Mitchell; Gonzalez-Lopez, Marcos et al. (2014) Small-molecule IAP antagonists sensitize cancer cells to TRAIL-induced apoptosis: roles of XIAP and cIAPs. Mol Cancer Ther 13:5-15|
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