The median survival time of men with prostate cancer that progresses to androgen independence is approximately two years. The goal of our Program is to elucidate the alterations in signal transduction and associated changes in gene expression that underlie prostate progression to the androgen independent state. Our Program brings together productive and experienced investigators at the University of Virginia and the University of Colorado with the complementary expertise needed to fulfill the stated goals. Our team includes experts in basic and clinical aspects of human prostate cancer biology (D. Theodorescu;Colorado), signal transduction and the androgen receptor (B. Paschal;Virginia), and microRNA regulation (A. Dutta;Virginia). Project 1 will determine how hypoxic signals are sensed by post-translational mechanisms and transduced into changes in gene expression that promote prostate cancer progression, including metastasis. Project 2 will use new mouse models to determine how kinases downstream of PI-3 kinase cooperate to drive prostate tumorigenesis. Project 3 will determine how changes in microRNA profiles regulate cell proliferation and prostate cancer progression to androgen independence. The three Projects are supported by three Cores that have a strong track record of providing support for Program members. Core A (Administration;Director, B. Paschal) will enhance productivity by facilitating communication between the Virginia and Colorado sites, and by fulfilling biostatistical needs (Biostatistician, M. Conaway) of the Program. Core B (Transgenic Models and Animal Imaging;Director, David Wotton) is directed by a mouse genetics expert who will develop genetically engineered murine models for prostate tumorigenesis, and assist with xenograft production. Core C (Tissue Analysis;Director, H. Frierson) will perform histological and immunohistochemical analysis of mouse and human prostate. Our team of basic and clinician scientists has a track record of collaboration and a shared vision of defining prostate cancer progression mechanisms. The long-term objective is to translate our understanding of prostate cancer progression mechanisms into the identification of new drug targets and pre-clinical models that recapitulate key aspects of the human disease.
Prostate cancer is the second leading cause of deaths due to cancer in North American men. Our research is designed to explain how prostate cancer progresses to a state that is resistant to current therapies. This knowledge base will enable the design of new therapeutic strategies.
| Kuscu, Canan; Kumar, Pankaj; Kiran, Manjari et al. (2018) tRNA fragments (tRFs) guide Ago to regulate gene expression post-transcriptionally in a Dicer-independent manner. RNA 24:1093-1105 |
| Hao, Yi; Bjerke, Glen A; Pietrzak, Karolina et al. (2018) TGF? signaling limits lineage plasticity in prostate cancer. PLoS Genet 14:e1007409 |
| Yang, Chun-Song; Melhuish, Tiffany A; Spencer, Adam et al. (2017) The protein kinase C super-family member PKN is regulated by mTOR and influences differentiation during prostate cancer progression. Prostate 77:1452-1467 |
| Agarwal, Neeraj; Dancik, Garrett M; Goodspeed, Andrew et al. (2016) GON4L Drives Cancer Growth through a YY1-Androgen Receptor-CD24 Axis. Cancer Res 76:5175-85 |
| Reon, Brian J; Dutta, Anindya (2016) Biological Processes Discovered by High-Throughput Sequencing. Am J Pathol 186:722-32 |
| Kumar, Pankaj; Kuscu, Canan; Dutta, Anindya (2016) Biogenesis and Function of Transfer RNA-Related Fragments (tRFs). Trends Biochem Sci 41:679-689 |
| Sakurai, Kouhei; Reon, Brian J; Anaya, Jordan et al. (2015) The lncRNA DRAIC/PCAT29 Locus Constitutes a Tumor-Suppressive Nexus. Mol Cancer Res 13:828-38 |
| Dillon, Laura W; Kumar, Pankaj; Shibata, Yoshiyuki et al. (2015) Production of Extrachromosomal MicroDNAs Is Linked to Mismatch Repair Pathways and Transcriptional Activity. Cell Rep 11:1749-59 |
| Kumar, Pankaj; Mudunuri, Suresh B; Anaya, Jordan et al. (2015) tRFdb: a database for transfer RNA fragments. Nucleic Acids Res 43:D141-5 |
| Earl, Julie; Rico, Daniel; Carrillo-de-Santa-Pau, Enrique et al. (2015) The UBC-40 Urothelial Bladder Cancer cell line index: a genomic resource for functional studies. BMC Genomics 16:403 |
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