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 demonstrate that apoptotic responses can be 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 various apoptotic regulators including Bcl-2 family members, death receptors and caspases in the therapeutic responses to anticancer agents via induction of apoptotic and nonapoptotic cell death. Another line of our work shows that PUMA-dependent apoptosis plays an important role in the injury of intestinal stem and epithelial cells induced by DNA damage and inflammation. We are further exploring potential interactions of cell death and DNA repair in injury-induced stem regeneration using mouse models.
Based on the mechanistic insights, 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
- Magness ST, Puthoff BJ, Crissey MA, Dunn JC, Henning SJ, Houchen CW, Kaddis JS, Kuo CJ, Li L, Lynch JP, Martin MG, May RJ, Niland JC, Olack B, Qian D, Stelzner M, Swain J, Wang F, Wang J, Wang X, Yan K, Yu J, Wong MH. A multi-center study to standardize reporting and analyses of fluorescence-activated cell sorted murine intestinal epithelial cells. Am J Physiol Gastrointest Liver Physiol. 2013 Oct 15;305(8):G542-51. PMID: 23928185. PMCID: PMC3798732.
- 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. 2013 Aug 21. [Epub ahead of print]. PMID: 23966620. PMCID: PMC3823684.
- Chen, X., Meng, J., Yue, W., Yu, J., Yang, J., Yao, Z. and Zhang, L. (2014) Fibulin-3 suppresses Wnt/β-catenin signaling and lung cancer invasion. Carcinogenesis 2014 Jan 30. [Epub ahead of print]. PMID: 24480807. PMCID: PMC4123641.
- Sun J, Knickelbein K, He K, Chen D, Dudgeon C, Shu Y, Yu J, Zhang L. Aurora Kinase Inhibition Induces PUMA via NF-κB to Kill Colon Cancer Cells. Mol Cancer Ther. 2014 May;13(5):1298-308. doi: 10.1158/1535-7163.MCT-13-0846. Epub 2014 Feb 21. PMID: 24563542. PMCID: PMC4013266.
- 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. PMID: 24637717. PMCID: PMC4327858.
- Chen D, Wei L, Yu J, Zhang L. Regorafenib inhibits colorectal tumor growth through PUMA-mediated apoptosis. Clin Cancer Res. 2014 Jul 1;20(13):3472-84. doi: 10.1158/1078-0432.CCR-13-2944. Epub 2014 Apr 24. PMID: 24763611. PMCID: PMC4079733.
- Chen D, Ming L, Zou F, Peng Y, Van Houten B, Yu J, Zhang L. TAp73 promotes cell survival upon genotoxic stress by inhibiting p53 activity. Oncotarget. 2014 Sep 30;5(18):8107-22. PMID: 25237903. PMCID: PMC4226670.
- 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. PMID: 25368155. 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. Sci Rep. 2015 Apr 10;5:8566. doi: 10.1038/srep08566. PMID: 25858503. [PubMed - in process]
- 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 Apr 13. doi: 10.1038/onc.2015.79. [Epub ahead of print]. PMID: 25867072.2
- Brown MF, Leibowitz BJ, Chen D, He K, Zou F, Sobol RW, Beer-Stolz D, Zhang L, Yu J. Loss of Caspase-3 sensitizes colon cancer cells to genotoxic stress via RIP1-dependent necrosis. Cell Death Dis. 2015 Apr 23;6:e1729. doi: 10.1038/cddis.2015.104. PMID: 25906152.