The overall goal of this Program is to develop nucleic acid therapeutics based on a mechanistic understanding of how these molecules modulate gene expression in vitro, and in vivo. The program consists of 4 projects and 2 Cores. Each project will investigate in a critical manner different approaches to, and aspects of, modulating gene expression in mammalian cells. The individual projects, and their Investigators are as follows: Kazuko Nishikura (Wistar Institute)- RNAi mediated squelching of Gene Expression in Mammalian Cells; Stephen Liebhaber (University of Pennsylvania)- RNA Decoys- aCP as a Model for Modulating Gene Expression in Erythroid Cells; Eric Pierce (University of Pennsylvania) and Kyong Yoon (Thomas Jefferson University, Philadelphia, PA)- Mechanisms of Gene Repair and Targeting in Embryonic Stem Cells; and Alan M. Gewirtz (University of Pennsylvania)- Developing Nucleic Acid Therapeutics. The projects are supported by the following Cores: Nucleic Acid Synthesis- Ponzy Lu (University of Pennsylvania)-Director; Administration- A. Gewirtz, Director. Each of the project directors is an established investigator with a substantial interest in the biology of gene expression at the transcriptional and translational levels. Each Project Leader brings to the effort a different expertise, which is non-overlapping and highly complementary. Accordingly, the groups' interactions will be highly synergistic and result in a program, which is truly greater than the sum of its parts. All of the investigators are ultimately interested in translating their laboratory findings into the development of more reliable, and more efficient, molecules for silencing gene expression. It is our belief that such molecules will have an important impact on the diagnosis, and treatment of neoplastic diseases.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Research Program Projects (P01)
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Study Section
Subcommittee G - Education (NCI)
Program Officer
Forry, Suzanne L
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University of Pennsylvania
Internal Medicine/Medicine
Schools of Medicine
United States
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Kini, Hemant K; Kong, Jian; Liebhaber, Stephen A (2014) Cytoplasmic poly(A) binding protein C4 serves a critical role in erythroid differentiation. Mol Cell Biol 34:1300-9
Ji, Xinjun; Wan, Ji; Vishnu, Melanie et al. (2013) ?CP Poly(C) binding proteins act as global regulators of alternative polyadenylation. Mol Cell Biol 33:2560-73
Ji, Xinjun; Kong, Jian; Liebhaber, Stephen A (2011) An RNA-protein complex links enhanced nuclear 3' processing with cytoplasmic mRNA stabilization. EMBO J 30:2622-33
Jin, Shenghao; Zhao, Huiwu; Yi, Yan et al. (2010) c-Myb binds MLL through menin in human leukemia cells and is an important driver of MLL-associated leukemogenesis. J Clin Invest 120:593-606
Deleavey, Glen F; Watts, Jonathan K; Alain, Tommy et al. (2010) Synergistic effects between analogs of DNA and RNA improve the potency of siRNA-mediated gene silencing. Nucleic Acids Res 38:4547-57
Waggoner, Shelly A; Johannes, Gregg J; Liebhaber, Stephen A (2009) Depletion of the poly(C)-binding proteins alphaCP1 and alphaCP2 from K562 cells leads to p53-independent induction of cyclin-dependent kinase inhibitor (CDKN1A) and G1 arrest. J Biol Chem 284:9039-49
Rudnick, Stephen I; Swaminathan, Jyothishmathi; Sumaroka, Marina et al. (2008) Effects of local mRNA structure on posttranscriptional gene silencing. Proc Natl Acad Sci U S A 105:13787-92
Flagler, K; Alexeev, V; Pierce, E A et al. (2008) Site-specific gene modification by oligodeoxynucleotides in mouse bone marrow-derived mesenchymal stem cells. Gene Ther 15:1035-48
Pattanayak, Vikram; Gifford, Lida K; Lu, Ponzy et al. (2008) Observed versus predicted structure of fluorescent self-quenching reporter molecules (SQRM): caveats with respect to the use of ""stem-loop"" oligonucleotides as probes for mRNA folding. RNA 14:657-65
Tang, XinJing; Swaminathan, Jyothishmathi; Gewirtz, Alan M et al. (2008) Regulating gene expression in human leukemia cells using light-activated oligodeoxynucleotides. Nucleic Acids Res 36:559-69

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