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.

Public Health Relevance

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.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Research Program Projects (P01)
Project #
Application #
Study Section
Special Emphasis Panel (ZCA1-RPRB-O (J1))
Program Officer
Mohla, Suresh
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Virginia
Schools of Medicine
United States
Zip Code
Dey, Bijan K; Pfeifer, Karl; Dutta, Anindya (2014) The H19 long noncoding RNA gives rise to microRNAs miR-675-3p and miR-675-5p to promote skeletal muscle differentiation and regeneration. Genes Dev 28:491-501
Yan, Chao; Liu, Degang; Li, Liwei et al. (2014) Discovery and characterization of small molecules that target the GTPase Ral. Nature 515:443-7
Zhang, Y; Kim, J; Mueller, A C et al. (2014) Multiple receptor tyrosine kinases converge on microRNA-134 to control KRAS, STAT5B, and glioblastoma. Cell Death Differ 21:720-34
Negishi, Masamitsu; Wongpalee, Somsakul P; Sarkar, Sukumar et al. (2014) A new lncRNA, APTR, associates with and represses the CDKN1A/p21 promoter by recruiting polycomb proteins. PLoS One 9:e95216
Kumar, Pankaj; Anaya, Jordan; Mudunuri, Suresh B et al. (2014) Meta-analysis of tRNA derived RNA fragments reveals that they are evolutionarily conserved and associate with AGO proteins to recognize specific RNA targets. BMC Biol 12:78
Bettegowda, Chetan; Sausen, Mark; Leary, Rebecca J et al. (2014) Detection of circulating tumor DNA in early- and late-stage human malignancies. Sci Transl Med 6:224ra24
Dancik, Garrett M; Owens, Charles R; Iczkowski, Kenneth A et al. (2014) A cell of origin gene signature indicates human bladder cancer has distinct cellular progenitors. Stem Cells 32:974-82
Nickerson, Michael L; Dancik, Garrett M; Im, Kate M et al. (2014) Concurrent alterations in TERT, KDM6A, and the BRCA pathway in bladder cancer. Clin Cancer Res 20:4935-48
Floyd, Desiree Hunt; Zhang, Ying; Dey, Bijan K et al. (2014) Novel anti-apoptotic microRNAs 582-5p and 363 promote human glioblastoma stem cell survival via direct inhibition of caspase 3, caspase 9, and Bim. PLoS One 9:e96239
Sun, D; Layer, R; Mueller, A C et al. (2014) Regulation of several androgen-induced genes through the repression of the miR-99a/let-7c/miR-125b-2 miRNA cluster in prostate cancer cells. Oncogene 33:1448-57

Showing the most recent 10 out of 42 publications