New assays for drug development: During my second postdoctoral fellowship at Boston Children’s Hospital, Harvard Medical School, I focused on finding new ways to target late stage/aggressive prostate cancer. Despite recent diagnostic and therapeutic advances, prostate cancer continues to occur with both high incidence and significant mortality in the male Western population. In spite of this fact, few new therapeutic targets outside of the androgen receptor axis have been identified. Lately, I have identified Antizyme Inhibitor (AZIN1) as a new target for advanced prostate cancer. I further describe novel tools and approaches to target this molecule. Whereas silencing AZIN1 is a potential therapeutic strategy, the development of small molecule inhibitors of the AZIN1 function could have even greater efficacy and broader clinical utility. To date, however, no efforts have been reported toward developing small molecule inhibitors of this attractive pathway. Fluorescence resonance energy transfer (FRET) assay, one of the most advanced and desirable method with extensive application range, performs assays to directly detect the oligomerization state and potential molecular interactions. I have developed and optimized a selective FRET assay that will identify small molecules that inhibit antizyme-AZIN1 binding. Ablation of AZIN1 activity could provide an innovative approach to extend the lives of patients suffering from advanced prostate cancer and improve their quality of life as now they have limited treatment options.
Selected Publication:
- Ghalali A, Rice JM, Kusztos A, Jernigan FE, Zetter BR, Rogers MS. Developing a novel FRET assay, targeting the binding between Antizyme-AZIN. Sci Rep. 2019 Mar 15;9(1):4632.