Photo of Zhi-Min Yuan,   M.D. M.S. Ph.D.

Zhi-Min Yuan, M.D. M.S. Ph.D.

Harvard T.H. Chan School Of Public Health

Harvard T.H. Chan School Of Public Health
Phone: (617) 432-2139

Zhi-Min Yuan, M.D. M.S. Ph.D.

Harvard T.H. Chan School Of Public Health


  • Professor, Genetics and Complex Diseases, Harvard T.H. Chan School Of Public Health
  • Director, John B. Little Center, Harvard T.H. Chan School Of Public Health


Research Abstract

Functional characterization of the p53 pathway has been a major research area of my laboratory for more than 10 years. Apart from the characterization of signals and pathways important for p53 regulation, we’ve also investigated the biological function of p53 under normal and pathological conditions. Our understanding of p53 biology has

reached to the point where we are actively conducting translational research to explore the therapeutic potential of p53.

Our research also involves the DNA damage responses, radiation-induced response in particular. We are interested inelucidation of the signaling mechanisms that regulate cellular response to stress and in examining how stress is converted into intracellular signals that control cell behavior in the context of carcinogenesis. Our long-term goal is to gain a better understanding of the biology of carcinogenesis, which would then allow us to design effective strategies for prevention, early detection, and treatment of cancer.


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  • Gong L, Pan X, Abali GK, Little JB, Yuan ZM. Functional interplay between p53 and Δ133p53 in adaptive stress response. Cell Death Differ 2019. PubMed
  • Molloy ME, Lewinska M, Williamson AK, Nguyen TT, Kuser-Abali G, Gong L, Yan J, Little JB, Pandolfi PP, Yuan ZM. ZBTB7A governs estrogen receptor alpha expression in breast cancer. 2018; 10:273-284. PubMed
  • Williamson AK, Zhu Z, Yuan ZM. Epigenetic mechanisms behind cellular sensitivity to DNA damage. Cell Stress 2019; 2:176-180. PubMed
  • Kuser-Abali G, Gong L, Yan J, Liu Q, Zeng W, Williamson A, Lim CB, Molloy ME, Little JB, Huang L, Yuan ZM. An EZH2-mediated epigenetic mechanism behind p53-dependent tissue sensitivity to DNA damage. Proc Natl Acad Sci U S A 2018; 115:3452-3457. PubMed
  • Gong L, Pan X, Lim CB, de Polo A, Little JB, Yuan ZM. A functional interplay between Δ133p53 and ΔNp63 in promoting glycolytic metabolism to fuel cancer cell proliferation. Oncogene 2018. PubMed
  • Gerarduzzi C, de Polo A, Liu XS, El Kharbili M, Little JB, Yuan ZM. Human epidermal growth factor receptor 4 (Her4) Suppresses p53 Protein via Targeting the MDMX-MDM2 Protein Complex: IMPLICATION OF A NOVEL MDMX SER-314 PHOSPHOSITE. J Biol Chem 2016; 291:25937-25949. PubMed
  • de Polo A, Luo Z, Gerarduzzi C, Chen X, Little JB, Yuan ZM. AXL receptor signalling suppresses p53 in melanoma through stabilization of the MDMX-MDM2 complex. 2016. PubMed
  • de Araujo PR, Gorthi A, da Silva AE, Tonapi SS, Vo DT, Burns SC, Qiao M, Uren PJ, Yuan ZM, Bishop AJ, Penalva LO. Musashi1 Impacts Radio-Resistance in Glioblastoma by Controlling DNA-Protein Kinase Catalytic Subunit. Am J Pathol 2016; 186:2271-8. PubMed
  • Gong L, Pan X, Yuan ZM, Peng J, Chen J. p53 coordinates with Δ133p53 isoform to promote cell survival under low-level oxidative stress. 2016; 8:88-90. PubMed
  • Ha CS, Michalek JE, Elledge R, Kelly KR, Ganapathy S, Su H, Jenkins CA, Argiris A, Swords R, Eng TY, Karnad A, Crownover RL, Swanson GP, Goros M, Pollock BH, Yuan ZM. p53-Based strategy to reduce hematological toxicity of chemotherapy: A proof of principle study. Mol Oncol 2015. PubMed
  • Liu XS, Genet MD, Haines JE, Mehanna EK, Wu S, Chen HI, Chen Y, Qureshi AA, Han J, Chen X, Fisher DE, Pandolfi PP, Yuan ZM. ZBTB7A Suppresses Melanoma Metastasis by Transcriptionally Repressing MCAM. Mol Cancer Res 2015. PubMed
  • Qi M, Ganapathy S, Zeng W, Zhang J, Little JB, Yuan ZM. UXT, a novel MDMX-binding protein, promotes glycolysis by mitigating p53-mediated restriction of NF-κB activity. 2015. PubMed
  • Su H, Ganapathy S, Li X, Yuan ZM, Ha CS. p53-Based Strategy for Protection of Bone Marrow From Y-90 Ibritumomab Tiuxetan. Int J Radiat Oncol Biol Phys 2015. PubMed
  • Liu XS, Little JB, Yuan ZM. Glycolytic metabolism influences global chromatin structure. 2015; 6:4214-25. PubMed
  • Liu XS, Haines JE, Mehanna EK, Genet MD, Ben-Sahra I, Asara JM, Manning BD, Yuan ZM. ZBTB7A acts as a tumor suppressor through the transcriptional repression of glycolysis. Genes Dev 2014; 28:1917-28. PubMed
  • Ganapathy S, Xiao S, Yang M, Qi M, Choi DE, Ha CS, Little JB, Yuan ZM. A low-dose arsenic-induced p53 protein-mediated metabolic mechanism of radiotherapy protection. J Biol Chem 2014; 289:5340-7. PubMed
  • Cai X, Yuan ZM. Stochastic modeling and simulation of the p53-MDM2/MDMX loop. J Comput Biol 2009; 16:917-33. PubMed
  • Wu XL, Gu MM, Huang L, Liu XS, Zhang HX, Ding XY, Xu JQ, Cui B, Wang L, Lu SY, Chen XY, Zhang HG, Huang W, Yuan WT, Yang JM, Gu Q, Fei J, Chen Z, Yuan ZM, Wang ZG. Multiple synostoses syndrome is due to a missense mutation in exon 2 of FGF9 gene. Am J Hum Genet 2009; 85:53-63. PubMed
  • Huang Y, Zhang J, McHenry KT, Kim MM, Zeng W, Lopez-Pajares V, Dibble CC, Mizgerd JP, Yuan ZM. Induction of cytoplasmic accumulation of p53: a mechanism for low levels of arsenic exposure to predispose cells for malignant transformation. Cancer Res 2008; 68:9131-6. PubMed
  • Lopez-Pajares V, Kim MM, Yuan ZM. Phosphorylation of MDMX mediated by Akt leads to stabilization and induces 14-3-3 binding. J Biol Chem 2008; 283:13707-13. PubMed
  • Kawai H, Lopez-Pajares V, Kim MM, Wiederschain D, Yuan ZM. RING domain-mediated interaction is a requirement for MDM2's E3 ligase activity. Cancer Res 2007; 67:6026-30. PubMed
  • Lehtinen MK, Yuan Z, Boag PR, Yang Y, Villén J, Becker EB, DiBacco S, de la Iglesia N, Gygi S, Blackwell TK, Bonni A. A conserved MST-FOXO signaling pathway mediates oxidative-stress responses and extends life span. Cell 2006; 125:987-1001. PubMed
  • Toyoshima M, Shimura T, Adiga SK, Taga M, Shiraishi K, Inoue M, Yuan ZM, Niwa O. Transcription-independent suppression of DNA synthesis by p53 in sperm-irradiated mouse zygotes. Oncogene 2005; 24:3229-35. PubMed
  • Katayama H, Sasai K, Kawai H, Yuan ZM, Bondaruk J, Suzuki F, Fujii S, Arlinghaus RB, Czerniak BA, Sen S. Phosphorylation by aurora kinase A induces Mdm2-mediated destabilization and inhibition of p53. Nat Genet 2003; 36:55-62. PubMed
  • Kawai H, Wiederschain D, Yuan ZM. Critical contribution of the MDM2 acidic domain to p53 ubiquitination. Mol Cell Biol 2003; 23:4939-47. PubMed
  • Wiederschain D, Kawai H, Gu J, Shilatifard A, Yuan ZM. Molecular basis of p53 functional inactivation by the leukemic protein MLL-ELL. Mol Cell Biol 2003; 23:4230-46. PubMed
  • Gu J, Kawai H, Nie L, Kitao H, Wiederschain D, Jochemsen AG, Parant J, Lozano G, Yuan ZM. Mutual dependence of MDM2 and MDMX in their functional inactivation of p53. J Biol Chem 2002; 277:19251-4. PubMed
  • Shimura T, Inoue M, Taga M, Shiraishi K, Uematsu N, Takei N, Yuan ZM, Shinohara T, Niwa O. p53-dependent S-phase damage checkpoint and pronuclear cross talk in mouse zygotes with X-irradiated sperm. Mol Cell Biol 2002; 22:2220-8. PubMed