Zhi Sheng, Ph.D.
Breaking down cancer’s resistance
Why are some cancers immune to conventional therapies?
Dr. Zhi Sheng’s laboratory explores new and effective cancer therapies by dissecting molecular pathways that orchestrate cell survival and/or death and overcoming drug resistance in cancer.
Sheng and his researchers are particularly focused on glioblastoma multiforme, a lethal and incurable brain cancer that often recurs after conventional therapies such as resection, radiation therapy, and chemotherapy. Recent research findings from the Sheng Laboratory indicate that targeting the enzyme PIK3CB (a catalytic subunit of PI3K) selectively inhibits cell viability, making this gene a potential therapeutic target for Glioblastoma. The lab’s ongoing and future research aims to elucidate the mechanism underlying the selectivity of targeting PI3K in glioblastoma and developing 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 (the body’s cleaning out of damaged cells) 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 glioblastoma 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.
- Assistant Professor, Fralin Biomedical Research Institute at VTC
- Assistant Professor, Department of Internal Medicine, School of Medicine
Sheng KL, Pridham KJ, Sheng Z, Lamouille S, Varghese RT. (2019). Functional Blockade of the Small GTPase RAN Inhibits Glioblastoma Viability. Frontiers in Oncology 8: 662.
Liang Y, Dearnaley WJ, Alden NA, Solares MJ, Gilmore BL, Pridham KJ, Varano AC, Sheng Z, Alli E, Kelly DF. (2019). Correcting Errors in the BRCA1 Warning System. DNA Repair 73: 120-128.
Varghese RT, Young S, Pham LC, Liang Y, Pridham KJ, Guo S, Murphy SF, Kelly DF, and Sheng Z. (2018). Casein Kinase 1 Epsilon Regulates Glioblastoma Cell Survival. Scientific Reports 8(1).
- Pathologist, Department of Pathology, Affiliated Hospital of Anhui Medical University
- Lecturer, Department of Pathology, Anhui Medical University
- University of Massachusetts Medical School: Postdoctoral fellowship, Molecular Cancer Biology
- State University of New York Downstate Medical Center: Ph.D., Molecular and Cell Biology
- Shanghai Medical College, Fudan University: M.S., Biochemistry
- Shanghai Medical College, Fudan University: B.S,. Forensic Science