Common prostatic diseases include prostate cancer, benign prostatic hyperplasia (BPH) and prostatitis. These diseases are a cause of significant mortality and morbidity. Prostate specific antigen (PSA) is released at increased levels into the blood early in the development of these diseases and therefore is widely used for screening, diagnosing and monitoring of prostate cancer. However, PSA has clinical limitations as a screen for prostatic diseases due to its low sensitivity and specificity. There is an urgent need for information about the causes of individual variation in serum PSA levels. The long term goal of this KO1 proposal is to prepare Dr. Mubiru for an independent career focused on the development of NHP models and tools for the study of PSA biology. Dr. Mubiru is a dual-trained veterinarian/scientist with DVM, MS and PhD degrees. He has been involved in the development of transgenic mice as well as in identifying biomarkers for prostate cancer. Dr Mubiru will acquire skills in molecular and population genetics as they relate to prostatic diseases. Dr. J. Rogers, a geneticist and genomics expert will serve as his mentor. Dr. Leach, a Professor in the Dept. of Cellular and Structural Biology at UTHSCSA will serve as co-mentor. Dr. Mubiru will specifically study the prostate of two nonhuman primate species (baboon, rhesus) maintained at the Southwest Foundation for Biomedical Research (SFBR). Our hypothesis is that 1) nonhuman primate species are the best animal models to study PSA biology, 2) serum PSA levels in nonhuman primates are genetically determined, 3) factors relating to adiposity and obesity affect serum PSA concentration.
The specific aims of this proposal are i) study the anatomy and histology of the prostate of the baboon and rhesus, ii) investigate the influence of age and genetics on variation in PSA among these two species, iii) identify DNA polymorphisms in both the promoter regions of the PSA gene and exon 1 of the androgen receptor gene and assess the influence of these polymorphisms on variation in serum PSA levels, iv) investigate the relationship between obesity and its related phenotypes on one hand and serum PSA levels on the other.
The aims of this proposal will be addressed using multidisciplinary approaches and through collaborative studies.
