Dr. Li Urology Research Laboratory
The Urology Research Laboratory is a subdivision of the Department of Urology at the University of Kansas Medical Center. We conduct basic and translational research related to urological diseases, focusing primarily on human prostate cancers.
About Our Research
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. However, 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. This is called castration-resistant progression or CRPC. The biology at the molecular level for CRPC progression is not currently known or understood.
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 using a 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 agenta 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 that the PI3K/p110β and its downstream targets, AKT and SGK1, are involved in AR transactivation and prostate cancer progression. Based on these findings, we developed a novel p110β-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 start-up 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 five 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
- Determine the molecular mechanisms involved in AR protein stabilization; and
- Develop novel therapeutics using small peptide-based technology; and
- Examine Alternol action on human cancer cells.