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
Research ExpertiseThere are three major ongoing research areas in the lab: 1) cell death mechanisms in cancer cells, 2) intestinal stem cells in injury and carcinogenesis, and 3) cell death-targeted drug development. I discovered and extensively characterized the p53 target and Bcl-2 family apoptotic member PUMA. My lab has been investigating the role of the intrinsic and extrinsic apoptotic pathways in cancer biology and therapy, as well as crosstalk among apoptosis, necroptosis, and mitochondrial dysfunction triggered by anticancer therapies. We have also been elucidating the survival and killing mechanisms in normal intestinal stem cells (ISCs) during injury, regeneration and carcinogenesis focusing on distinct downstream targets of p53 and NF- B pathways. These mechanistic studies motivated us to pursue the development and discovery of small molecular cell death modulators. Our data indicate that cancer drivers play a key role in the responses to anticancer agents, which can be explored to widen the therapeutic index. The long term goal of our research is to identify novel mechanisms, targets and agents for cancer treatment and normal tissue protection. A wide variety of approaches are employed in our studies, including molecular and cell biology techniques, imaging, somatic knockout and knockin cancer cells, 3D intestinal primary cultures, engineered mouse models, intestinal injury and cancer animal models, computational biology, and correlative studies using clinical samples.
Selected PUBLICATIONS (from 99)View Dr. Yu's publications on PubMed
- Yu J, Zhang L, Hwang PM, Kinzler KW, Vogelstein B. PUMA induces the rapid apoptosis in colorectal cancer cells. Mol. Cell 2001 Mar 30;7(3):673-82. (Featured in Nature Reviews of Molecular Cell Biology 2:319, 2001)
- Yu J, Wang Z, Kinzler KW, Vogelstein B, Zhang L. PUMA mediates the apoptotic response to p53 in colorectal cancer cells. Proc. Natl. Acad. Sci. USA 2003 Mar 100:1931-1936.
- Qiu W, Carson-Walter EB, Liu H, Epperly M, Greenberger JS, Zambetti, GP, Zhang L, Yu J. PUMA regulates intestinal progenitor cell radiosensitivity and gastrointestinal syndrome. Cell Stem Cell. 2008 Jun 5;2(6):576-83. PMCID: PMC2892934
- Ming L, Sakaida T, Yue W, Jha A, Zhang L, and Yu J. Sp1 and p73 activate PUMA following serum starvation. Carcinogenesis. 2008 Oct;29(10):1878-84. PMCID: PMC2722853
- Sun Q, Ming L, Thomas SM, Wang Y, Chen Z, Ferris RL, Grandis JR, Zhang L, Yu J. PUMA mediates EGFR tyrosine kinase inhibitor-induced apoptosis in head and neck cancer cells. Oncogene. 2009 Jun 18;28(24):2348-57. PMCID: PMC2872091
- Qiu W, Carson-Walter EB, Kuan SF, Zhang L, Yu J. PUMA Suppresses Intestinal Tumorigenesis in Mice. Cancer Res. 2009 Jun 15;69(12):4999-5006. PMCID: PMC2872079
- Wang P, Zou F, Zhang X, Li H, Dulak A, Tomko RJ, Lazo JS, Wang Z, Zhang L, Yu J. MicroRNA-21 modulates G2/M checkpoint and cell cycle progression through Cdc25A. Cancer Res. 2009 Oct 15;69(20):8157-65. PMCID: PMC2763324
- Qiu W, Leibowitz B, Zhang L, Yu J. Growth factors protect intestinal stem cells from radiation-induced apoptosis by suppressing PUMA through the PI3K/AKT/p53 axis. Oncogene. 2010 Mar 18;29(11):1622-32. PMCID: PMC3076086
- Qiu W, Wang X., Leibowitz B., Liu H, Barker N, Okada H, Oue N, Yasui W, Clevers H, Schoen R, Yu J *, Zhang L. Chemoprevention by nonsteroidal anti-inflammatory drugs eliminates oncogenic intestinal stem cells via SMAC-dependent apoptosis. Proc Natl Acad Sci U S A. 2010 Nov 16;107(46):20027-32. * Co-corresponding author. PMCID: PMC2993406
- Mustata G, Li M, Zevola N, Bakan A, Zhang L, Epperly M, Greenberger JS, Yu J*, Bahar I. Development of small-molecule PUMA inhibitors for mitigating radiation-induced cell death. Curr Top Med Chem. 2011;11(3):281-90. * Co-Corresponding author. PMCID: PMC308601154.
- Sun Q, Zheng X, Zhang L, Yu J. Smac Modulates Chemosensitivity in Head and Neck Cancer Cells through the Mitochondrial Apoptotic Pathway. Clin Cancer Res. 2011 Apr 15;17(8):2361-72. PMCID: PMC3079009
- Qiu W, Wu B, Wang X, Buchanan M, Regueiro MD, Hartman D, Schoen RE, Yu J, Zhang L. PUMA-mediated intestinal epithelial apoptosis contributes to ulcerative colitis in humans and mice. J Clin Invest. 2011 May 2;121(5):1722-32. doi: 10.1172/JCI42917. PMCID: PMC3083802
- Leibowitz B, Qiu W, Liu H, Cheng T, Zhang L, Yu J. Uncoupling p53 functions in radiation-induced intestinal damage via PUMA and p21. Mol Cancer Res. 2011 May;9(5):616-25. PMCID: PMC3096742
- Qiu W, Liu H, Sebastini A, Sun Q, Wang H, Zhang L, Yu J. An apoptosis-independent role of SMAC in tumor suppression. Oncogene. 2013 May 9;32(19):2380-9. doi: 10.1038/onc.2012.265. Epub 2012 Jul 2. PMCID:PMC3751796
- Zheng X, He K, Zhang L, Yu J. Crizotinib induces PUMA-dependent apoptosis in colon cancer cells. Mol Cancer Ther. 2013 May;12(5):777-86. doi: 10.1158/1535-7163.MCT-12-1146. PMCID:PMC3651803
- He K, Zheng X, Zhang L, Yu J. Hsp90 inhibitors promote p53-dependent apoptosis through PUMA and Bax. Mol Cancer Ther. 2013 Nov;12(11):2559-68. PMCID:PMC3823684
- Leibowitz BJ, Wei L, Zhang L, Ping X, Epperly M, Greenberger J, Cheng T, Yu J. Ionizing irradiation induces acute haematopoietic syndrome and gastrointestinal syndrome independently in mice. Nat Commun. 2014 Mar 18;5:3494. doi: 10.1038/ncomms4494. PMCID: PMC4327858.
- Leibowitz B, Qiu W, Buchanan ME, Zou F, Vernon PV, Moyer MP, Yin X, Schoen RE, Yu J*, Zhang, L*. BID mediate selective killing of APC-deficient cells in intestinal tumor suppression by non-steroidal anti-inflammatory drugs. Proc Natl Acad Sci U S A. 2014 Nov 18;111(46):16520-5. * Co-corresponding author. PMCID: PMC4246283.
- Wang X, Wei L, Cramer J, Leibowitz B, Judge C, Epperly M, Greenberger J, Wang F, Li L, Stelzner M, Dunn J, Martin M, Lagasse E, Zhang L, Yu J. Pharmacologically blocking p53-dependent apoptosis protects intestinal stem cells and mice from radiation. Scientific Reports (2015).
- 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 (2015)
- Brown M, Leibowitz B, Chen D, He K, Zou F, Sobol R, Stolz D, Zhang L, Yu J. Loss of Caspase-3 sensitizes colon cancer cells to genotoxic stress via RIP1-dependent necrosis. Cell Death & Disease (2015)