Research interests in this laboratory focus on molecular mechanisms of hormone action via nuclear receptors and of cytoskeletal associated proteins on proliferation, differentiation, and apoptosis of normal and cancerous prostate cells. Research also emphasizes the study of mechanisms by which naturally occurring and/or synthetic compounds effect the chemoprevention and/or chemotherapy of prostate cancer. Lastly, through molecular biology and proteomic approaches, potentially useful genes will be discovered and used as tools for the detection and treatment of prostate cancer.

Specific Research Topics

1. Androgens, retinoic acids, vitamin C, vitamin E, selenium, and thyroid hormone are essential factors for growth and differentiation of prostatic cells. The promoters of prostate-specific genes are used as models to understand the interactions of these hormones/vitamins via their nuclear receptors regarding the molecular mechanisms controlling gene expression in the prostate and prostate cancer.

2. In collaboration efforts with other laboratories, projects concentrate on the usage of prostate-specific/tumor associated proteins as targets in conjunction with the utility of heat shock proteins for prostate cancer immunotherapy.

3. Several naturally occurring substances, especially phytochemicals and polyunsaturated fatty acids and metabolites, have been investigated for their chemopreventive effects on prostate cancer. In vitro and in vivo systems are used to elucidate the mechanism by which these compounds inhibit the growth of prostate cancer cells.

4. Efforts have been made to develop immunoassays for novel markers (i.e., hK2, PSA variant, and hAG2 ) in order to detect prostate cancer. A panel of more than several tens of specific monoclonal antibodies has been produced and used to select the best pairs of antibodies for immunometric assay of hK2 in patient's serum. Presently, a relatively large scale pre-clinical trial is being performed to determine the efficacy of the assay.

5. Molecular biology (e.g., subtraction cloning and microarray), genomics and proteomics (high resolution 2 dimensional electrophoresis in conjunction with mass spectrometry based amino acid sequencing and software-based analysis) technologies are used in the lab with assistance of Mayo core facilities to discover relevant genes (including novel genes) for prostate cancer. First, the genes discovered can be used to develop more sensitive, more specific, and less invasive means for early detection, diagnosis and management of prostate cancer. Second, through this gene discovery project, specific genes and cellular processing pathways preferentially used in prostate cancer cells may be defined, which, in turn, can be used as targets for cancer prevention and treatment purposes.

6. New cytoskeletal associated proteins have been identified and intensively studied for understaning of cancer progression and metastasis