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 ExpertiseApoptosis (programmed cell death) is a physiological process used by higher eukaryotes to selectively remove cells that are no longer needed, damaged or dangerous. Deregulated apoptosis contributes to a wide variety of diseases. My research focuses on the molecular mechanisms of apoptosis regulation in cancer biology and therapy.
There 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) apoptosis-targeted drug development. Our major focus is the regulation of BH3-only protein such as PUMA in apoptosis induced by cancer therapies targeting survival pathways and oncogenic kinases. We recently started to explore molecular switches controlling distinct apoptotic pathways, and apoptosis with other forms of cell death, i.e., autophagy, necrosis and mitotic catastrophe via mitochondria and bioenergetics. Using mouse models coupled with stem cell lineage marking and tracing, we are probing the role of apoptosis and stress response in intestinal damage, regeneration and carcinogenesis, currently focusing on the p53/PUMA/p21 and IAP/SMAC/NF- B pathways. Lastingly, we are engaged in developing small molecules as potential apoptosis-targeted therapies using cell-based assays as well as computational biology-assisted approaches. The long term goal of our research is to understand the complex role of apoptosis and its regulation, and identify novel targets in cell death pathways 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 cell lines, state-of-art 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
- 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.
- Wu B, Qiu W, Wang P, Yu H, Cheng T, Zambetti GP, Zhang L, Yu J. p53-independent Induction of PUMA Mediates Intestinal Apoptosis in Response to Ischemia Reperfusion. Gut. 2007 May;56(5):645-54.
- Sun Q, Sakaida T, Yue W, Gollin SM, Yu J. Chemosensitization of Head and Neck Cancer Cells by PUMA. Mol Cancer Ther. 2007 Dec;6(12):3180-8. PMID: 18089712.
- 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.
- Ming L, Sakaida T, Yue W, Jha A, Zhang L, Yu J. Sp1 and p73 activate PUMA following serum starvation. Carcinogenesis. 2008 Oct;29(10):1878-84.
- 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. Epub 2009 Jun 2. PMCID: PMC2872079.
- 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.
- 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. Epub 2009 Oct 13. 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. Epub 2009 Dec 7. PMCID: PMC3076086.
- Qiu W, Wang X, Leibowitz B, Liu H, Barker N, Okada H, Oue N, Yasui W, Clevers H, Schoen RE, 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. Epub 2010 Nov 1. * 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. 2010 Nov 4. [Epub ahead of print] * Corresponding author. PMCID: PMC3086011
- 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. Epub 2011 Jan 17. 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. Epub 2011 Apr 1. 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. Epub 2011 Mar 30. 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. 2012 Jul 2. doi: 10.1038/onc.2012.265. PMID: 22751125.
- Sun J, Sun Q, Brown M, Dudgeon C, Chandler J, Xu X, Shu Y, Zhang L and Yu J. The multi-targeted kinase inhibitor Sunitinib induces apoptosis in colon cancer cells via PUMA. PLoS One 2012;7(8):e43158. Epub 2012 Aug 17. PMID: 22912816 PMCID: PMC3422222.
- Qiu W, Liu H, Sebastini A, Sun Q, Wang H, Zhang L, Yu J. An apoptosis-independent role of SMAC in tumor suppression. Oncogene. 2012 Jul 2. 10.1038/onc.2012.265. [Epub ahead of print]. PMID: 22751125.
- Yuan HF, Huang H, Li XY, Guo W, Xing W, Sun ZY, Liang HP, Yu J, Chen DF, Wang ZG, Hao J, Xu X. A Dual AP-1 and SMAD Decoy ODN Suppresses Tissue Fibrosis and Scarring in Mice. J Invest Dermatol. 2012 Dec 6. doi: 10.1038/jid.2012.443. [Epub ahead of print]. PMID: 23223130.
- Spender LC, Carter MJ, O'Brien DI, Clark LJ, Yu J, Michalak EM, Happo L, Cragg MS, Inman GJ. Transforming Growth Factor-β directly induces PUMA during the rapid induction of apoptosis in Myc-driven B-cell lymphomas. J Biol Chem. 2012 Dec 14. [Epub ahead of print] PMID: 23243310.
- Peng R, Tong J, Li H, Yue, B., Zou, F., Yu J. and Zhang, L. Targeting Bax interaction sites reveals that only homo-oligomerization sites are essential for its activation. Cell Death Differ. 2013 May;20(5):744-54. doi: 10.1038/cdd.2013.4. Epub 2013 Feb 8. PMID: 23392123[PubMed - in process]. PMCID: PMC3619242 [Available on 2014/5/1]
- Zheng X, He K, Zhang L, Yu J. Crizotinib induces PUMA-dependent apoptosis in colon cancer cells. Mol Cancer Ther. 2013 Feb 20. [Epub ahead of print]
- 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.