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 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 cues from the microenvironment regulate intestinal renewal under hemostasis, as well as regeneration following injury. This is achieved via highly coordinated proliferation and lineage specification to carry out vital functions such absorption, secretion, and barrier against non-self. Mounting evidence indicates that intestinal stem cell (ISC) dysfunction impairs regeneration and leads to chronic inflammation, dysbiosis, cancer and other age-associated diseases. Research in Yu lab elucidates cancer driver-dependent regulation of cell death and regeneration, with the long-term goal to identify novel targets and agents to combat GI injury and cancer through the "normalization" of stem cell-niche interactions. We use a multidisciplinary and team approach, including molecular and cell biology, mouse models, patient derived organoids and xenografts, clinical samples, systems biology, and drug discovery.

Intestinal stem cell protection Damage to intestinal stem cells and the barrier "niche" increases the risk of cancer and poor therapeutic response. We showed that excessive cell death with persistent DNA damage leads to intestinal injury and carcinogenesis. Cell death and DNA damage repair coordinate ISC regeneration upon injury through a complex crosstalk with the niche, immune cells, and the gut microbiota. We are mechanistically dissecting these highly spatial and temporal interactions to identify novel targets and agents to facilitate intestinal regeneration. We identified p53-dependent apoptosis and STING-dependent Type 1 Interferon response as novel targets to improve intestinal regeneration upon chemoradiation.

Colon cancer biology and therapy Drivers such as mutant KRAS/BRAF, Wnt/Myc activation, and chromosomal instability (CIN) are strongly linked to progression, therapy resistance, and immune evasion in colon cancer. We have previous identified and extensively studied the Bcl-2 family protein PUMA as a critical mediator of drug-induced apoptosis. However, the mechanisms underlying cell death and antitumor immunity remain poorly understood. We are currently exploring proteostress as a therapeutic vulnerability in mutant KRAS colon cancers through the induction of immunogenic cell death (ICD). We hope to develop rationale drug combinations and biomarkers to aid subtype stratification and response prediction.

We are always looking for motivated students and fellows to join. If you share the passion, please contact Dr. Yu.

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

Publications

NCBI My Bibliography
https://www.ncbi.nlm.nih.gov/myncbi/jian.yu.1/bibliography/public/

Google Scholar (135 articles, over 23,000 citations, H-index 66)
https://scholar.google.com/citations?user=PfNbw24AAAAJ&hl=en

  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. PMID: 11463391. Featured by 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. PMID: 12574499.
  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. Featured by Cell Stem Cell 2: 517-518, 2008 and Nature Biotechnology 26 (7): 777, 2008.
  4. 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. *Co-corresponding author. PMID: 21041628.
  5. 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.
  6. 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. Featured by Nature Reviews Gastroenterology & Hepatology, doi:10.1038/nrgastro.2016.175
  7. Leibowitz BJ, Yang L, Wei L, Buchanan ME, Rachid M, Parise, RA, Beumer JH, Eiseman JL, Schoen RE, Zhang L, Yu J. Targeting p53-dependent stem cell loss for intestinal chemoprotection. Sci Transl Med. 2018 Feb 7;10(427). PMID: 29437148. Featured by Science 359: 6376, 2018, and Faculty 1000.
  8. Han Y, Peng Y, Fu Y, Cai C, Guo C, Liu S, Li Y, Chen Y, Shen E, Long K, Wang X, Yu J*, Shen H*, Zeng S*. MLH1 Deficiency Induces Cetuximab Resistance in Colon Cancer via Her-2/PI3K/AKT Signaling. Adv Sci (Weinh). 2020 Jul;7(13):2000112. *Co-corresponding author. PMID: 32670759.
  9. Ruan H, Li X, Xu X, Leibowitz BJ, Tong J, Chen L, Ao L, Xing W, Luo J, Yu Y, Schoen RE, Sonenberg N, Lu X, Zhang L, Yu J. eIF4ES209 phosphorylation licenses myc- and stress-driven oncogenesis. Elife. 2020 Nov 2;9. PMID: 33135632. Dataset. https://doi.org/10.5061/dryad.tb2rbnzxm
  10. Leibowitz BJ, Guangyi Zhao G, Liang Wei L, Ruan H, Michael Epperly M, Chen L, Xinghua Lu X, Greenberger JS, Zhang L, Yu J. Interferon Beta drives Intestinal Regeneration after Radiation. Sci Adv. 2021 Oct 8;7(41):eabi5253. doi: 10.1126/sciadv.abi5253. PMID: 34613772. Dataset. https://doi.org/10.5061/dryad.pvmcvdnm2

(Last updated on 11/16/2021)