The long-term goal of our laboratory is to understand how the antiapoptotic protein survivin and its splice variants (e.g., survivin-2B, survivin-ΔEx3, survivin-3B) play a role in tumorigenesis and cancer progression. Survivin plays critical roles in regulating the cell cycle and mitosis. The prominent expression of survivin appears in all human malignancies, and is low or absent in most normal tissue. This suggests that it would be an ideal target for cancer therapy.
Using cancer cell-based survivin-reporter systems via high throughput screening (HTS) of compound libraries, followed by in vitro and in vivo analyses of HTS-derived hit-lead compounds, we identified a small molecule FL118 and demonstrated that FL118 has significant antitumor activity in several human xenograft tumor animal models. We actively pursue opportunities to translate our laboratory findings to clinics.
Our current research focuses on: the molecular mechanisms of action of FL118, the DMPK profile and potential side effects induced by FL118 treatment. In addition, survivin isoforms perform different functions in distinct subcellular compartments. We characterized several novel survivin splicing variants and we are addressing their functions in cancer development and cancer treatment.
Our lab work is supported by NIH/NCI, DOD and many public or private foundations.