Zhi Sheng, Ph.D.
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
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.
For a more complete listing of Zhi Sheng's publications, visit PubMed.
Education and Training
- University of Massachusetts Medical School: Postdoctoral fellowship, Molecular Cancer Biology
- State University of New York Downstate Medical Center: PhD, Molecular and Cell Biology
- Shanghai Medical College, Fudan University: MS, Biochemistry
- Shanghai Medical College, Fudan University: BS, Forensic Science
- Affiliated Hospital of Anhui Medical University
Pathologist, Department of Pathology
- Anhui Medical University
Lecturer, Department of Pathology
- 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).
- Varghese RT, Lian Y, Guan T, Franck CT, Kelly DF, Sheng Z. (2016). Survival kinase genes present prognostic significance in glioblastoma. Oncotarget.
- Murphy SF, Varghese RT, Lamouille S, Guo S, Pridham KJ, Kanabur P, Osimani AM, Sharma S, Jourdan J, Rodgers CM, Simonds GR, Gourdie RG, Sheng Z. (2016). Connexin 43 Inhibition Sensitizes Chemoresistant Glioblastoma Cells to Temozolomide. Cancer Research 76(1): 139-49.
- Gilmore BL, Winton CE, Demmert AC, Tanner JR, Bowman S, Karageorge V, Patel K, Sheng Z, Kelly DF. (2015). A Molecular Toolkit to Visualize Native Protein Assemblies in the Context of Human Disease. Scientific Reports 5.
- Li T, Murphy S, Kiselev B, Bakshi KS, Zhang J, Eltahir A, Zhang Y, Chen Y, Zhu J, Davis RM, Madsen LA, Morris JR, Karolyi DR, LaConte SM, Sheng Z, Dorn HC. (2015). A New Interleukin-13 Amino-Coated Gadolinium Metallofullerene Nanoparticle for Targeted MRI Detection of Glioblastoma Tumor Cells. Journal of the American Chemical Society 137(24): 7881-8.
- Pohlmann ES, Patel K, Guo S, Dukes MJ, Sheng Z, Kelly DF. (2015). Real-time visualization of nanoparticles interacting with glioblastoma stem cells. Nano Letters 15(4): 2329-35.
- Guo S, Liang Y, Murphy SF, Huang A, Shen H, Kelly DF, Sobrado P, Sheng Z. (2015). A rapid and high content assay that measures cyto-ID-stained autophagic compartments and estimates autophagy flux with potential clinical applications. Autophagy 25.
- Ma L, Shan Y, Bai R, Xue L, Eide CA, Ou J, Zhu LJ, Hutchinson L, Cerny J, Khoury HJ, Sheng Z, Druker BJ, Li S, Green MR. (2014). A therapeutically targetable mechanism of BCR-ABL-independent imatinib resistance in chronic myeloid leukemia. Science Translational Medicine 6(252).
- Sheng Z, Murphy SF, Guo S, Green MR. (2014). A diphtheria toxin negative selection in RNA interference screening. In: Wajapeyee N (Ed.), Cancer Genomics and Proteomics (Methods in Molecular Biology). (pp. 59-72).New York City: Humana Press (Springer).
- Jang HN, Lee M, Loh TJ, Choi S-W, Oh HK, Moon H, Cho S, Hong S-E, Kim DH, Sheng Z, Green MR, Park D, Zheng X, Shen H. (2014). Exon 9 skipping of apoptotic caspase-2 pre-mRNA is promoted by SRSF3 through interaction with exon 8. Biochimica et Biophysica Acta 1839(1): 25-32.