Assistant Professor, Virginia Tech Carilion Research Institute Assistant Professor, Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine Assistant Professor of Internal Medicine, Virginia Tech Carilion School of Medicine
Program Focus
The overarching research goal of the Dr. Zhi Sheng’s laboratory at the Virginia Tech Carilion Research Institute is to develop new and effective cancer therapies using the following strategies and approaches: (1) Identify new and effective cancer therapeutic targets by dissecting molecular pathways that orchestrate the cell survival and/or death; and (2) Overcome drug resistance in cancer.
Researchers in the Sheng Laboratory are particularly interested in glioblastoma multiforme (GBM). GBM is a lethal and incurable brain cancer, and it often recurs after conventional therapies such as resection, radiation therapy, and chemotherapy. Recent research findings from the Sheng Laboratory indicate that PIK3CB (a catalytic subunit of PI3K) confers a prognostic significance in recurrent GBM. Targeting PIK3CB—but not other PI3K subunits—selectively inhibits cell viability, making this gene a potential therapeutic target for GBM. Ongoing and future research focuses on elucidating the mechanism underlying the selectivity of targeting PI3K in GBM and developing PIK3CB-based therapies tailored to GBM patients with a high risk of recurrence.
By using a large-scale RNA interference screening, Dr. Sheng and his team identified 82 genes (termed autophagy-regulating genes, ARGs) that regulate autophagy in cancer. Of particular interest to the researchers is an ARG named long non-coding RNA 00467, which is an RNA gene with no protein-coding potential. The scientists are currently probing the molecular underpinnings of noncoding RNA-regulated autophagy in cancer and exploring the therapeutic potential of this new autophagy regulatory pathway in antagonizing drug resistance.
Dr. Sheng’s laboratory also collaborates with Dr. Robert Gourdie, who developed the FDA-approved wound-healing drug ACT1 that targets connexin 43. The scientists repurposed ACT1 into a possible treatment to circumvent the resistance of GBM to temozolomide, a DNA alkylating agent used as the front line treatment. Future studies include unveiling the molecular mechanism of temozolomide sensitization by ACT1 and implementing ACT1 treatment into the clinic.
Selected Publications
Guo S, Pridham KJ, Virbasius CM, He B, Zhang L, Varmark H, Green MR, Sheng Z. (2018). A large-scale RNA interference screen identifies genes that regulate autophagy at different stages . Scientific Reports 8 (1) .
Pridham KJ, Varghese RT, Sheng Z. (2017). The Role of Class IA Phosphatidylinositol-4,5-Bisphosphate 3-Kinase Catalytic Subunits in Glioblastoma . Frontiers in Oncology 7 (312) .
Liang Y, Dearnaley WJ, Varano AC, Winton CE, Gilmore BL, Alden NA, Sheng Z, Kelly DF. (2017). Structural analysis of BRCA1 reveals modification hotspot . Science Advances 3 (9) .
Guo S, Pridham KJ, Virbasius CM, He B, Zhang L, Varmark H, Green MR, Sheng Z. (2018). A large-scale RNA interference screen identifies genes that regulate autophagy at different stages. Scientific Reports 8(1).
Pridham KJ, Varghese RT, Sheng Z. (2017). The Role of Class IA Phosphatidylinositol-4,5-Bisphosphate 3-Kinase Catalytic Subunits in Glioblastoma. Frontiers in Oncology 7(312).
Liang Y, Dearnaley WJ, Varano AC, Winton CE, Gilmore BL, Alden NA, Sheng Z, Kelly DF. (2017). Structural analysis of BRCA1 reveals modification hotspot. Science Advances 3(9).