Jian Yu, PhD
Associate 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.
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. We understand the role and regulation of proapoptotic proteins, such as the Bcl-2 family, death receptor 5, caspases in the therapeutic response to cancer therapies targeting survival pathways and oncogenic kinases. We recently started exploring molecular switches controlling apoptosis with other forms of cell death, i.e., necrosis and mitotic catastrophe. Using knockout and transgenic mouse models coupled with intestinal stem cell lineage marking and tracing, we have been probing the role of apoptotic and stress responses in intestinal damage, regeneration and carcinogenesis, currently focusing on the p53 and NF-kB pathways. Lastingly, we are engaged in developing small molecules as potential apoptosis-targeted therapies using a multidisciplinary approach. The long term goal of our research is to understand molecular mechanisms of cell death, and identify novel targets and agents for cancer treatment and normal stem cell protection.
A wide variety of approaches are employed in our studies, including molecular and cell biology techniques, engineering somatic knockout and knockin cancer cells, cell imaging, transgenic and knockout mouse models, injury and cancer models, and correlative studies using clinical samples.
Selected PublicationsView Dr. Yu's publications on PubMed
- 1. 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.
- Yu J*, Yue W, Wu B, Zhang L. PUMA Sensitizes Lung Cancer Cells to Chemotherapeutic Agents and Irradiation. Clin Cancer Res. 2006 May 1;12(9):2928-36. * Corresponding author
- 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. Epub 2009 May 4. 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, Wang X, Leibowitz B, Yang W, Zhang L, Yu J. PUMA-mediated apoptosis drives chemical hepatocarcinogenesis in mice. Hepatology, 2011 Oct;54(4):1249-58. doi: 10.1002/hep.24516. PMCID: PMC3184207
- 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. PMID:22751125. 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
- Qiu W, Wang X, Buchanan ME, He K., Sharma R., Zhang L, Wang Q* and Yu J*. ADAR1 is essential for intestinal homeostasis and stem cell maintenance. Cell Death Dis. 2013 Apr 18;4:e599. doi: 10.1038/cddis.2013.125. * Co-corresponding author. PMCID:PMC3641348
- 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
- Yu J. Intestinal stem cell injury and protection during cancer therapy. Transl Cancer Res 2013;2(5):384-396. doi: 10.3978/j.issn.2218-676X.2013.07.03. PMCID: PMC3966653.
- Zhang L, Yu J. Role of apoptosis in colon cancer biology, therapy and prevention. Curr Colorectal Cancer Rep. 2013 Dec;9(4). doi: 10.1007/s11888-013-0188-z. PMCID: PMC3836193.
- Leibowitz BJ, Wei L, Zhang L, Ping X, Epperly M, Greenberger J, Cheng T, Yu J. Ionizing irradiation induces acute hematopoietic syndrome and gastrointestinal syndrome independently in mice. Nature Communications, 2014 Mar 18, doi: 10.1038/ncomms4494. PMID: 24637717