Biotechnology/Bioinformatics. Our efforts are aimed at 1) defining the prostate transcriptome, that component of the human genome that is actively utilized or expressed in the prostate; 2) developing database tools that allow for the virtual analyses and comparisons of tissue or cellular transcriptomes, in health and disease. In the latter case, we have designed a database of expressed prostate genes, the Prostate Expression Database (PEDB) that can be used for virtual expression analysis and is available for public use; and 3) developing DNA (and protein) array-based technology for quantitative gene expression measurements.
Biology of Cancer Metastasis. During the process of cancer metastasis, a complex series of events occurs that involves extensive modulation of cell-cell contacts and cell contact with the extracellular matrix. We reported that hevin, a gene previously identified as modulating lymphocyte trafficking through endothelium, is down-regulated in metastatic prostate cancers. We have also recently identified novel members of the Toll-like family of proteins (TIL3 and TIL4), that may also exhibit adhesive properties in addition to their regulatory roles in the immune system.
Biology of Prostate Carcinogenesis. We have used the technologies described above in practical applications for the discovery of novel prostate-specific genes and for the identification of gene expression changes in the progression of prostate cancer. One gene, a novel prostate-specific serine protease with ~40% identity to PSA, is a current focus of our work. The regulatory region of the gene is being studied in order to determine why the expression is prostate-specific and androgen-regulated.
A second effort involves a study of the molecular heterogeneity of prostate cancers through the use of single-cell analyses. Single prostate cancer cells are microdissected from fresh or frozen tissue sections using "patch clamp" techniques. We are currently exploring methods for amplifying the entire complement of mRNA with high-fidelity such that whole cDNA probes can be constructed for use with microarray technology.
Nelson PS, Clegg N, Arnold H, Ferguson C, Bonham M, White J, Hood L, Lin B.
(2002) The program of androgen-responsive genes in neoplastic prostate epithelium. Proc Natl Acad Sci USA. 3;99:11890-5..
Martin DB, Gifford DR, Wright ME, Keller A, Yi E, Goodlett DR, Aebersold R and Nelson PS. (2004). Quantitative Proteomic Analysis of Proteins Released by Neoplastic Prostate Epithelium. Cancer Research 64:1589-94.
Kim TS, Heinlein C, Hackman R, and Nelson PS. (2006) Phenotypic Analysis of Mice Lacking the Tmprss2 protease. Mol Cell Biol. 26(3):965-75.
Bavik C, Coleman I, Dean J, Knudsen B, and Nelson PS. (2006) The gene expression program of prostate fibroblast senescence modulates neoplastic epithelial cell proliferation through paracrine mechanisms. Cancer Res. 55(2):794-802.
Pritchard C, Coil D, Hsu L, and Nelson PS (2006) The Contributions of Normal Variation and Genetic Background to Mammalian Gene Expression. Genome Biology:7(3):R26.