Dr. Dean Bacich received his Ph.D. at the University of Adelaide in Australia. He subsequently trained at Memorial Sloan Kettering Cancer Center, NY as a post-doctoral fellow in the laboratory of Dr. William Fair M.D. and Dr. Warren (Skip) Heston, Ph.D. Dr. Bacich continued his train at the Cleveland Clinic when Dr. Heston’s lab was recruited there. In 2002 he was recruited to an independent faculty position at the University of Pittsburgh as an Assistant Professor in the Department of Urology. In 2014, Dr. Bacich was recruited to the Department of Urology at the UT Health San Antonio as an Associate Professor.
Ph.D., University of Adelaide, Australia (1997)
BS, University of Adelaide, Australia (1989)
Dr. Bacich’s research focuses on prostate cancer, specifically the prostate cancer antigen, Prostate Specific Membrane Antigen (PSMA), which is a unique folate hydrolase that is highly expressed in prostate cancer and is an independent marker of prostate cancer aggression. He has demonstrated that PSMA gives cells a growth advantage in physiological levels of folate, as well as demonstrating that moderate expression of PSMA is sufficient to drive prostate carcinogenesis, and follow this finding up by demonstrating that inhibiting the enzymatic activity of PSMA, neutralizes its tumor-initiating activity. My lab also demonstrated that both folate levels and PSMA inhibitors are able to modify the ability of PSMA expressing cells to invade in vitro.
The folate hydrolase activity spurred his interest in the effect of folate on prostate cancer initiation and progression. This area of research is particularly relevant, given the requirement for folate for cancer cell division as well as it being required for genomic stability and methylation reactions, thus it can have positive or negative consequences depending on the stage of cancer, and yet patient intake of folate can be easily modified by dietary modification. As prostate cancers almost universally express high levels of PSMA, we hypothesized that prostate tumors were able to take up higher levels of circulating folate and that this would allow a tumor cell lacking growth regulation to proliferate more quickly. We found that our patients had a wide range of fasting serum folates, varying more than 20 fold. In addition, when we examined their tumors, we found that those in the highest quintiles for serum folate had tumors that were proliferating on average 6 times as fast as tumors from men in the lowest quintile for serum folate. These findings led oncologist to advise their patients taking folic acid supplements to stop doing so, and were part of the report by the New Zealand government that affected their policy decision regarding folic acid fortification of the NZ diet. These findings were made by my lab, working closely with my colleague Denise O’Keefe and her laboratory.
While PSMA clearly plays an important role in prostate cancer, in the neuroscience field it was known by another name: Naaladase. This refers to its enzymatic activity using n-acetyl-aspartyl-glutamate (NAAG) as a substrate. NAAG is a major neuroprotective peptide and the third-most prevalent neurotransmitter found in the mammalian nervous system. I developed the PSMA knockout mice and examined the role of PSMA/Naaladase in response to stroke and nerve crush injury, finding that when PSMA is absent, mice recover much faster from these injuries than wild-type mice, and implicating PSMA inhibition as a therapeutic target for a wide array of neurologic damage. Additionally, we have demonstrated that mice lacking the PSMA gene or wild-type mice given PSMA inhibitors enhance memory in a novel object recognition test. We are currently using these mice to examine the role PSMA has on nerve damage during bladder dysfunction during diabetes.