My research focuses on elucidating two nuclear receptors (NRs), vitamin D receptor (VDR) and Testicular receptor 4 (TR4) and their ligand-induced signals for their impacts on the prostate, bladder cancer, and other hormone-related diseases by utilizing biochemical/molecular approaches and genetically engineered animal models.
In the vitamin D projects, we focus on two areas. (1) The first is the chemotherapy and chemopreventive effects of vitamin D on urologically-related cancers, including prostate cancer and bladder cancer. We applied molecular approaches and cell and mice carcinogenesis models to study the underlying molecular mechanisms by which vitamin D/VDR inhibits prostate and bladder carcinogenesis. (2) The second is investigating the impacts of the vitamin D/VDR signal to the response of non-muscle invading bladder cancer to intravesical Bacillus Calmette-Guerin (BCG) immunotherapy in experimental models. In order to dissect VDR in different cellular compartments to mediate anti-tumor activity as well as immune response, tissue-specific VDR knockout mice are being established in my laboratory.
TR4 belongs to the NR superfamily that controls a broad range of biologic programs. Via knockout mice studies, we discover TR4 roles in anti-aging and anti-prostate cancer which reinforce the strong correlation between aging and prostate cancer for which peak incidence and mortality rates occur in the older population. Dysfunction of TR4, including gene mutations and abnormal nucleocytoplasmic translocation found in human prostate cancer compromises TR4 protective effects, thereby promoting cancer. Many directions, such as identifying the upstream modulators, dissecting the TR4-mediated signaling pathways, and analyzing TR4 gene/protein profile from cancer patients are ongoing. Our ultimate goal is to design preventive and/or therapeutic approaches that exploit the responsible factors or pathways to stop or slow down prostate cancer progression, as well as to retard other aging-related diseases.