Our laboratory has cloned and characterized the expression of the mRNA encoding prostate-specific membrane antigen (PSMA); sequenced human and mouse PSMA DNA; generated PSMA knockout mice;identified the PSMA enhancer: established it as a peptide carboxypeptidase with preferred substrates of polygammaglutamated folate and N-acetylaspartylglutamate (NAAG).
We observed that PSMA is strongly upregulated in cancer and observed that PSMA is also strongly expressed on all human tumor neovasculature. Our laboratory is examining ways to target PSMA both for therapy and for imaging.
In addition to PSMA as a target for therapy in cancer, PSMA expression has been studied in the brain and is known by neurobiologists as NAALADASE and serves to inactivate the brain peptide NAAG. NAAG has been identified to play a major role in brain function as a ligand for metabotropic glutamate receptor 3 and is related to short-term memory consolidation and other aspects of brain function. Because PSMA (NAALADASE) is the major mechanism of NAAG inactivation, We are working with collaborators to establish the role of PSMA (NAALADASE) using our knockout models for establishing the modulating impact of NAAG function in the CNS.
We are also examining therapeutic approaches to other genito-urinary tumors such as bladder cancer and kidney cancer. In kidney cancer, we are examining the mechanism of action of a recently identified novel plant-based toxin that has a strong specificity for kidney cancer identified as Englerin A.