Message from the Director of Research
"We are the one of the largest urologic research programs in the nation with 7 research laboratories and nearly $4 million in research grants in 2008."
Welcome to Urologic Research at UC Davis! We are the one of the largest urologic research programs in the nation with 7 research laboratories and nearly $4 million in research grants in 2008. We have active basic science, translational and clinical research programs in the areas of prostate, bladder, kidney, and pediatric urological diseases.
The prostate cancer program is the major focus and is aimed to understand the mechanism of castration-resistant prostate cancer (CRPC), to identify molecular targets and to develop therapeutic approaches for CRPC. Androgen regulation is studied in mechanistic detail with regards to aberrant AR activation by kinases and transcription factors, cytokines, intracrine androgens, microRNAs, and coregulations. The focus on androgen receptor signaling pathway and cross-talk with intracellular signaling pathways, particularly tyrosine kinase signaling pathways, has led to identification of several key molecular targets and translation into preclinical and clinical trials. The research programs within the Department created a mutually supportive research environment that fosters exchange and collaboration with Prostate Cancer Program at UC Davis Cancer Center.
In addition to prostate cancer, the urothelial cancer initiative has been established to study bladder cancer molecular profiles. We have an active stem cancer program to investigate both the mechanisms and biological markers involved in cellular development. The studies on induction of human embryonic stem cells into becoming a more specialized cell type, urothelium will gain the potential of being able to regenerate a human organ such as the bladder, and obtain crucial insights into the causes of bladder cancer.
Another research program is focused on the disparities in quality of care for urologic cancers supported by a three-year grant from the Department of Defense to examine data from hundreds of thousands of cancer patients to study patterns of care and their impact on patient outcomes.
Research Highlights and Major Discoveries
- Mechanism of androgen receptor aberrant activation by NF-κB2/p52 in prostate cancer cells (Kung, Evans, Gao; Cancer Res, 2010).
- Aberrant activation of androgen receptor in a new neuropeptide-autocrine model of androgen-insensitive prostate cancer. (Kung, Evans; Cancer Res, 2009)
- Interleukin-6 regulates androgen synthesis in prostate cancer cells (Kung, Evans, Gao; Clin Cancer Res, 2009).
- Unveiled mechanisms of Interleukin-6 action: Interleukin-6 undergoes transition from growth inhibitor associated with neuroendocrine differentiation to stimulator accompanied by androgen receptor activation during LNCaP prostate cancer cell progression (Gao; Prostate, 2007).
- Mechanism of NF-κB2/p52 activation through Stat3 activation of NF-κB p100 processing involves CBP/p300-mediated acetylation (Gao; PNAS, 2006).
- Impairment of the DNA repair and growth arrest pathways by p53R2 silencing enhances DNA damage-induced apoptosis in a p53-dependent manner in prostate cancer cells (Kung, Mudryj, de Vere White; Mol Cancer Res, 2008).
- Discovery of an androgen-regulated miRNA suppresses Bak1 expression and induces androgen-independent growth of prostate cancer cells (Tepper, Evans, Kung, de Vere White; PNAS, 2007).
- Mechanism of inappropriate activation of androgen receptor by relaxin via β-catenin pathway (Tepper, de Vere White, Kung; Oncogene, 2008).
- Discovery of male germ cell-associated kinase, a male-specific kinase regulated by androgen, is a coactivator of androgen receptor in prostate cancer cells (de Vere White, Chen, Tepper, Kung; Cancer Res, 2006).
- A Phase II Trial of the Src-kinase inhibitor AZD0530 in patients with advanced castration-resistant prostate cancer: a California Cancer Consortium Study. (Lara, Evans, Gandara; Anti-Cancer Drugs, 2009).
- Src Family Kinase Oncogenic Potential and Pathways in Prostate Cancer As Revealed By AZD0530. (Kung, Evans; Oncogene, 2008).
- Autophagy Blockade Sensitizes Prostate Cancer Cells towards Src Family Kinase Inhibitors. (Kung, Evans, Lam; Genes & Cancer, 2010).
- Effect of the specific Src family kinase inhibitor saracatinib on osteolytic lesions using the PC-3 bone model. (Gao, Kung, Evans; Mol Cancer Ther, 2010).
- Nrdp1-Mediated regulation of ErbB3 expression by the androgen receptor in androgen-dependent but not castrate-resistant prostate cancer cells. (Ghosh, de Vere White, Tepper, Gandour-Edwards, Carraway; Cancer Res, 2010)
- Bladder wall transplantation--long-term survival of cells: implications for bioengineering and clinical application. (Kurzrock, Tissue Eng Part A, 2010)
- Genome-wide analysis of androgen receptor binding and gene regulation in two CWR22-derived prostate cancer cell lines. (Kung, Ghosh, Mudryj, Endocrine-related Cancers, 2010)
- ERK regulates calpain2 induced AR cleavage to low molecular weight forms in CWR22 relapsed prostate tumor cell lines. (Kung, Ghosh, Mudryj, J. Biol. Chem, 2010)
- Androgen Receptor regulation of Vitamin D receptor in response of castration-resistant prostate cancer cells to 1α-Hydroxyvitamin D5 – a calcitriol analog (Ghosh, Genes and Cancer, 2010)