Zhi Sheng, PhD
Assistant Professor, VTC Research Institute
Assistant Professor, Biomedical Sciences and Pathobiology, College of Veterinary Medicine at Virginia Tech
Research Program Summary
Glioblastoma, a lethal and incurable brain cancer, often recurs after conventional therapies such as resection, radiation therapy, and chemotherapy, possibly because cancer stem cells in glioblastoma (termed as glioma stem cells) are spared by these treatments. Chronic myeloid leukemia (CML) is characterized by a fusion tyrosine kinase BCR-ABL sufficient and necessary for malignant transformation in CML. Imatinib (Gleevec or STI571) that inhibits BCR-ABL kinase activity is currently the first-line therapy in CML. Nevertheless, many patients relapse after a period of treatment, possibly because of the drug resistance exhibited by leukemic stem cells. Therefore, new therapies should specifically aim at eradicating cancer stem cells. Autophagy, apoptosis, necrosis, mitotic catastrophe, and senescence are forms of cell death critical for homeostasis in normal tissues. They are often misregulated in cancer stem cells and contribute to therapeutic resistance, however. The research in my laboratory aims to elucidate the molecular mechanisms by which cell death is misregulated in cancer stem cells of glioblastoma or CML. Genome-wide RNA interference screen is a novel functional high-throughput screening approach widely used in studying cancer genetics. Many new oncogenes or tumor suppressor genes have been identified using such a screen. My laboratory will use this approach to address several critical questions in cancer research: (1) autophagy regulation in glioblastoma or CML; (2) regulation of mitotic catastrophe in glioblastoma; (3) therapeutic resistance in glioblastoma and CML; and (4) development of novel therapeutics to eradicate cancer stem cells.
Education and Training
- 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
- University of Massachusetts Medical School
- Zhang H, Peng C, Hu Y, Li H, Sheng Z, Chen Y, Sullivan C, Cerny J, Hutchinson L, Higgins A, Miron P, Zhang X, Brehm MA, Li D, Green MR, Li S. (2012). The Blk pathway functions as a tumor suppressor in chronic myeloid leukemia stem cells. Nat Genet.
- Den RB, Kamrava M, Sheng Z, Werner-Wasik M, Dougherty E, Martinucchi M, Lawrence YR, Hegarty S, Hyslop T, Andrews DW, Glass J, Friedman DP, Green MR, Camphausen K, Dicker AP. (2012). A phase I study of the combination of sorafenib with temozolomide and radiation therapy for the treatment of primary and recurrent high-grade gliomas. Int. J Radiat. Oncol. Biol. Phys.
- Sheng Z, Ma L, Green MR. (2011). The BCR-ABL oncoprotein suppresses autophagy through transcriptional regulation of mTOR expression by activating transcription factor 5. Blood, 118(10):2840-2848.
- Sheng Z, Li L, Zhu LH, Smith TW, Demers A, Ross AH, Moser RP, and Green MR. (2010). A genome-wide RNA interference screen reveals an essential CREB3l2-ATF5-MCL1survival pathway in malignant glioma with therapeutic implications. Nat. Med, 16:671-677.
- Sheng Z, Evans KS, and Green MR. (2010). An activating transcription factor 5-mediated survival pathway as a target for cancer therapy. Oncotarget, 1(6):457-460.
- Sheng Z, Wang S, and Green MR. (2009). Transcription and signaling pathways involved in BCR-ABL-mediated misregulation of 24p3 and 24p3R. EMBO J, 28:866-876.