Jian Yu, PhD
Professor of Pathology
Dr. Yu is a member of the University of Pittsburgh Cancer Institute, an affiliated member of the Division of Experimental Pathology, and a preceptor of the Cellular and Molecular Pathology Graduate Training Program. Dr. Yu holds a secondary appointment as Professor of Radiation Oncology.
Hillman Cancer Center
Research Pavilion Suite 2.26H
5117 Centre Avenue
Pittsburgh, PA 15213
Office Phone: 412-623-7786
- BS - Sichuan University, Chengdu, Sichuan, P.R. China, 1991
- PhD - Johns Hopkins University, 2001
Apoptosis, a form of programmed cell death is used by a multi-cellular organism to selectively remove cells that are no longer needed, damaged or dangerous. Defects in apoptosis contribute to a wide variety of human diseases. My research focuses on the role and regulation of apoptosis in cancer biology and therapy.
Apoptosis evasion is a common feature of human cancer. Work from us and others demonstrates that apoptotic responses are differentially regulated in the normal and cancer cells depending on their genetic background and expression of key apoptotic mediators. Such differences can be exploited to selectively eliminate cancer cells while preserving normal tissues including tissue-specific stem cells. We have previously identified the Bcl-2 family protein PUMA as a critical mediator of apoptosis induced by a wide range of anticancer drugs through both p53-dependent and -independent mechanisms. We are currently exploring the role of additional Bcl-2 family members, death receptors and caspases in the therapeutic responses to anticancer agents via induction of apoptotic and nonapoptotic cell death. On the other hand, excessive cell death plays an important role in intestinal injury and carcinogenesis induced by DNA damage and inflammation via p53-dependent and independent mechanism, which impairs intestinal stem cell function. We are exploring potential regulators and interactions of cell death and the DNA damage response in intestinal stem cell injury and regeneration in vivo.
Based on mechanistic insights from above studies, we have been actively developing novel apoptosis modulators using a multidisciplinary approach combining molecular and cell biology, biochemistry and computer modeling. A wide range of techniques and models are used in our studies, including engineering somatic knockout and knock in cancer cell lines, genetically modified mouse models, mouse and human crypt culture, and clinical samples.
Selected PublicationsView Dr. Yu's publications on PubMed
- Uttam S, Pham HV, LaFace J, Leibowitz B, Yu J, Brand RE, Hartman DJ, Liu Y. Early prediction of cancer progression by depth-resolved nanoscale maps of nuclear architecture from unstained tissue specimens. Cancer Res. 2015 Nov 15;75(22):4718-27. PMID: 26383164. PMCID: PMC4651746.
- He K, Zheng X, Li M, Zhang L, Yu J. mTOR inhibitors induce apoptosis in colon cancer cells via CHOP-dependent DR5 induction upon 4E-BP1 dephosphorylation. Oncogene. 2016 Jan 14;35(2):148-57. Epub 2015 Apr 13. PMID: 25867072. PMCID: PMC4603992.
- Wang Y, Wang X, Flores ER, Yu J, Chang S Y. A Dysfunctional telomeres induce p53-dependent and independent apoptosis to compromise cellular proliferation and inhibit tumor formation. Aging Cell. 2016 Apr 26. PMID: 27113195.
- He K, Chen D, Ruan H, Li X., Tong J, Xu X, Zhang L, Yu J. BRAFV600E-dependent Mcl-1 stabilization leads to Everolimus resistance in colon cancer cells. Oncotarget 2016 June 24. doi: 10.18632/oncotarget.10277. [Epub ahead of print].
- Tong J, Tan S, Zou F, Yu J, Zhang L. (2016) FBW7 mutations mediate resistance of colorectal cancer to targeted therapies by blocking Mcl-1 degradation. Oncogene (In Press).