Jian Yu, PhD
Professor of Pathology

Dr. Yu
Dr. Yu is a member of UPMC Hillman Cancer Center, an affiliated member of the Division of Experimental Pathology, and training faculty of the Cellular and Molecular Pathology Graduate Training Program and Pitt-CMU MSTP training program. Dr. Yu holds a secondary appointment as Professor of Radiation Oncology.

Office Location:
UPMC Hillman Cancer Center
Research Pavilion Suite 2.26H
5117 Centre Avenue
Pittsburgh, PA 15213

Contact Information:
Office Phone: 412-623-7786
Fax: 412-623-7778
Email: yuj2@upmc.edu

Education

  • BS - Sichuan University, Chengdu, Sichuan, P.R. China, 1991
  • PhD - Johns Hopkins University, 2001

Research Expertise

The gastrointestinal epithelium is the fastest renewing tissue in an adult mammal and maintained by tissue specific stem cells. Cell-intrinsic programs and environmental cues regulate intestinal homeostasis and regeneration following injury via coordinated actions of stem cell activation, proliferation, lineage specification to perform highly specialized and vital functions such absorption, secretion and barrier against non-self. Mounting evidence indicates that intestinal stem cell (ISC) dysfunction plays a key role in GI pathology ranging from inflammation, cancer to age-associated diseases. Research in Yu lab elucidates cancer driver-dependent regulation of cell death mechanisms, with the long term goal to identify druggable targets and novel agents to combat GI pathology through cell death manipulation, including selective protection of normal intestinal stem cells and killing of cancer cells. Approaches employed include molecular and cell biology, mouse models, 3D primary intestinal cultures, drug discovery and clinical samples.

Intestinal stem cell protection Damage to intestinal stem cells and their niche leads to acute and chronic GI injury, and increased risk for inflammation and cancer. Our work indicates that excessive cell death associated with DNA damage contributes to intestinal injury and carcinogenesis via both p53-dependent and independent mechanisms. We are exploring novel interactions of cell death, the DNA damage response, and stem cell-niche crosstalk in intestinal injury and regeneration in vivo, and pharmacologic approaches for ISC protection by selectively blocking p53-dependent pathological cell apoptosis and inflammation-induced niche dysregulation.

Colon cancer biology and therapy Resistance to cell death is a common feature of cancer, and linked to cancer initiation, progression and immune evasion. We have previously identified and extensively studied the Bcl-2 family protein PUMA as a critical mediator of apoptosis induced by a wide range of anticancer drugs in colon cancer cells following DNA damage and inhibition of oncogenic kinases. We are currently exploring driver-mediated translation and metabolic addictions to increase immunogenic cell death and therapeutic responses focusing on APC/Myc and RAS/RAF pathways. Related studies include rational combination of agents and biomarker discovery for predicting therapeutic responses.

Awards and Honors

2001 Michael A. Shanoff Research Excellence Award (The top honor in thesis research), Johns Hopkins University School of Medicine
2003 Young Clinical Scientist Award, The Flight Attendant Medical Research Institute
2004 The Hillman Fellow of Innovative Cancer Research
2005 The Alliance for Cancer Gene Therapy Young Investigator Award
2008 University of Pittsburgh Cancer Institute Junior Scholar Award
2010 American Cancer Society Research Scholar Award
2011 University of Pittsburgh Innovator Award

Selected Publications

Complete Listing of Publications (NCBI Biography)

  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)
  2. 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.
  3. 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. PMID:22751125. PMCID:PMC3751796. (Featured in Cell Stem Cell 2: 517-518, 2008 and Nature Biotechnology 26 (7): 777, 2008).
  4. 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.
  5. 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. PMID:24637717. PMCID: PMC4327858.
  6. 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.
  7. 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. PMID: 25858503. PMCID: PMC4392360.
  8. 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. PMID: 25867072. PMCID: PMC4603992.
  9. 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. PMID: 27351224.
  10. Wei L, Leibowitz BJ, Wang X, Epperly M, Greenberger J, Zhang L, Yu J. Inhibition of CDK4/6 protects against radiation-induced intestinal injury in mice. J Clin Invest. 2016 Oct 4. PMID: 27701148. PMCID: PMC5096907. DOI: 10.1172/JCI88410 (Highlighted in Nature Reviews Gastroenterology & Hepatology, doi:10.1038/nrgastro.2016.175)
  11. Li X, Li M, Ruan H, Qiu W, Xu X, Zhang L, Yu J. Co-targeting translation and proteasome rapidly kills colon cancer cells with mutant RAS/RAF via ER stress. Oncotarget. 2017 Feb 7;8(6):9280-9292. PMID: 28030835 PMCID: PMC5354731 DOI: 10.18632/oncotarget.14063
  12. Tong J, Wang P, Tan S, Chen D, Nikolovska-Coleska Z, Zou F, Yu J, Zhang L. Mcl-1 Degradation Is Required for Targeted Therapeutics to Eradicate Colon Cancer Cells. Cancer Res. 2017 May 1;77(9):2512-2521. PMID: 28202514 DOI: 10.1158/0008-5472.CAN-16-3242

(Last updated on 7/1/2017)