Research Team | Dr. Benyi Li
Urology Research Laboratory
The Urology Research Laboratory is a subdivision of the Department of Urology at KU Medical center. We are conducting basic and translational research related to Urological diseases, mainly focusing on human prostate cancers.
Prostate cancer is the most commonly diagnosed cancer and the second leading cause of cancer related deaths among American men. If treated during the time it is confined to the prostate, it is curable with definitive therapy but currently there is no known cure for metastatic prostate cancer. Progression can be delayed but not halted or reversed. Presently, metastatic cancer can be treated by androgen suppression that only delays the time to progression, but eventually the cancer will become resistant and no longer respond to treatment (so called castration-resistant progression or CRPC). It is not fully known about the biology at the molecular level for CRPC progression.
The etiology of prostate tumorigenesis and CRPC relapse may have various molecular causes, but in each scenario, the androgen receptor (AR) expression is maintained. Recent studies from our group and others demonstrated that AR-dependent signaling is required for prostate cancer development in early stage and CRPC progression in late stage. We also demonstrated that removing AR protein by small interference RNA (siRNA) technique caused a profound apoptotic cell death in AR-native prostate cancer cells regardless of their androgen dependency, demonstrating the essential role of the AR in cellular survival of prostate cancers. Systemically delivered AR silencing agent by nanoparticles eradicated prostate cancer xenografts in nude mice, which provides a new hope for metastatic prostate cancer patients although further clinical testing is needed.
The goal of Dr Li’s laboratory is to uncover the mechanisms responsible for cancer development and progression at a molecular level, and subsequently to develop novel therapeutic approaches for effective treatment. In the past several years we have identified the PI3K/p110 and its downstream targets AKT and SGK1 are involved in AR transactivation and prostate cancer progression. Based on these findings, we developed a novel p110-specific inhibitor BL140 to treat metastatic prostate cancers. Currently the project is ongoing at the preclinical stage. In addition, a small peptide strategy has been developed to trigger AR protein degradation in prostate cancer cells. A startup biotech company “ARtide Therapeutics LLC” was established to commercialize this small peptide technology.
The natural compound Alternol was purified from a fungi fermentation. We demonstrated that Alternol triggers ROS-dependent apoptotic cell death preferentially in malignant but not benign cells. We also identified 14 cellular proteins that are the Alternol-interacting proteins including 5 metabolic enzymes. Recently we determined that the metabolic enzyme XDH/XO is responsible for Alternol-induced ROS accumulation in prostate cancer cells. Further investigation is ongoing to fully elucidate Alternol action on human cancer cells.
Our research directions are:
- Determination of the molecular mechanisms involved in AR protein stabilization; and
- Development of novel therapeutics using small peptide-based technology; and
- Examination of Alternol action on human cancer cells.