Description:

Please join the Department of Pharmacology for a Works-in-Progress presentation by Xianpeng Liu and Andrey Ugolkov. 

Xianpeng Liu, Ph.D. - Postdoctoral Fellow, Kiyokawa Lab

"Function of the non-canonical ubiquitin activating enzyme UBA6 in breast cancer"

Ubiquitination plays critical roles in many diseases including cancer. The function of ubiquitin activating enzyme E1 in breast cancer is unknown. Our preliminary data revealed unexpected function of UBA6 in breast cancer. We also applied our novel Orthogonal-Ubiquitin-Transfer (OUT) technology in profiling E1-specific targets in HEK293 cells. This proteome-wide screen revealed overlapping yet distinctive substrate pools of ubiquitination initiated by UBA6 and UBA1, indicating differential functions of two E1s. Our ongoing work in UBA6 conditional knockout mice and the identification of the key UBA6-specific targets functioning in tumorigenesis and/or progression will provide more clues in the treatment of breast cancer.

Andrey Ugolkov, M.D., Ph.D. - Research Associate Professor, Center for Developmental Therapeutics

"GSK-3 inhibitor 9-ING-41 enhances genotoxic therapy of GBM leading to cure from intracranial brain tumor"

Glycogen Synthase Kinase-3 (GSK-3) has been identified as a potential therapeutic target for the treatment of GBM. We found that treatment with GSK-3 inhibitor 9-ING-41 in combination with the DNA alkylator CCNU significantly increased CCNU anti-tumor activity against orthotopic glioblastoma xenografts. The treatment with CCNU+9-ING-41 resulted in “apparent cure” for all mice with intracranial GBM6 and GBM12 tumors, as supported by histological evaluation that revealed a complete absence of cancer cells in mouse brain. Our results suggest that 9-ING-41, a novel clinical drug candidate, enhances the efficacy of genotoxic therapy for human GBM, and warrants consideration for clinical evaluation.