Yi Sun

Yi Sun, MD, PhD

Lawrence-Krause Research Professor of Radiation Oncology
Director of Cancer Biology Division

Med Sci I, Room 4424B
1301 Catherine St
Ann Arbor, MI 48109-5637



Dr. Yi Sun received his medical training in China in the early 80s and obtained his PhD at the University of Iowa in 1989. He received his postdoctoral training at the National Cancer Institute (USA) in the1990s. Following 8 years at Parke-Davis/Pfizer as a research fellow, he joined the faculty of University of Michigan in 2003 and was promoted to full professor in 2008. He was elected as a Fellow of the American Association for the Advancement of Science in 2012.

Dr. Sun has over 30 years of cancer research experience. His laboratory is mainly focused on validation of Cullin-RING ubiquitin ligase (CRL) as a promising cancer target for anti-cancer drug discovery. Since his cloning in 1999 of SAG (Sensitive to Apoptosis Gene) (MCB, 1999), also known as RBX2, a RING component of SCF (Skp1-Cullins-F box proteins) E3 ubiquitin ligase, Dr. Sun’s laboratory has studied this key molecule, including its stress responsiveness, biochemical activity, and its roles in embryonic development and tumorigenesis, along with studies on SAG-associated F-box proteins, including β-TrCP, FBXW7 and FBXW2. Specifically, we characterized several biologically significant proteins as novel substrates of SAG-SCF E3 ligase, including procaspase-3 (Neoplasia, 2006); c-Jun (Cancer Res, 2007); HIF-1α (Oncogene, 2008); p27 (Carcinogenesis, 2008); IκBα (JCB, 2007, Free Rad Biol Med, 2010); NOXA (Clinic Cancer Res, 2010, 2017); DEPTOR (Mol. Cell, 2011); NF1 (Dev. Cell, 2011); Erbin (JCB, 2015), XRCC4 (Mol Cell, 2016), MFN1 (JCI Insight, 2019), SHOC2 (Cell Reports, 2019), b-Catenin (Nat Commun. 2019), and MSX2 (PNAS, 2019). We also used conditional knockout mouse models to study the role of Sag in KrasG12D-induced tumorigenesis in the lung (JCI, 2014); the skin (JCB, 2015), and prostate tumorigenesis induced by Pten-loss (Mol Cancer, 2016).  Most recently, we found that inhibition of protein neddylation would regulate stem cell proliferation and differentiation (PNAS, 2016), reprogram energy metabolism (JCI Insight, 2019) and inhibit cilia formation (Protein & Cell, 2019); FBXW2 regulates growth and migration/invasion of lung cancer cells (Nat Commun. 2017, 2019); negative cross-talk between two neddylation E2s UBE2M and UBE2F (Mol. Cell, 2018); and negative cross-talk between RAS and mTORC1 signals, controlled by FBXW7 (Cell Reports, 2019); FBXW7 mediates early DNA damage response (NAR, 2019); and LSD1 promotes FBXW7 degradation (PNAS, 2019).

Dr. Sun has published 222 peered reviewed scientific papers and review articles. His work has been continuously supported by the National Cancer Institute (NCI). Dr. Sun has served as editorial board member of 7 scientific journals and several NCI study section review panels. Dr. Sun has been invited to present his work at numerous national and international meetings.

Areas of Interest

  • Cullin-RING ligase (CRL) and its RING component, SAG, in tumorigenesis and development of targeted cancer therapy
  • Protein neddylation in tumorigenesis and discovery of small molecule inhibitors for targeted cancer therapy.

Clinical Interests

  • Phase II clinical trials with MLN4924+Doceltaxol for the treatment of stage IV lung cancer.

Honors & Awards

  • 2018: Co-recipient of Dr. Clyde and Helen Wu Award in International Understanding, offered by the Wu Family China Center for Health Initiatives at the Columbia University, Vagelos College of Physicians and Surgeons 
  • 2012: Fellow, The American Association for the Advancement of Science


  • PhD, University of Iowa, 1989


  • 1R01 CA156744, (PI: Sun), 05/01/2011-03/31/2021, National Institutes of Health, The role of FBXW2 as a novel tumor suppressor that cross-talks with oncogenic βTrCP and SKP2, Role: Principal Investigator.
  • 1R01-CA-200651, 06/01/2016-05/31/2021, National Institutes of Health, Targeting the APC/Cdc20 E3 ubiquitin ligase for chemoradiation sensitization, Role: Co-Investigator.

Published Articles via PubMed

Published Articles or Reviews

Selected from 222 publications

  • Yang, F., Xu, J., Li, H., Tan, M., Xiong, X., and Sun, Y.: FBXW2 suppresses migration and invasion of lung cancer cells via promoting ubiquitylation and degradation of β-catenin. Nat. Communications, 2019 March 27, 10:1382 | https://doi.org/10.1038/s41467-019-09289-5.
  • Lan, H., Tan, M., Zhang, Q., Li, H., Xiong, X. and Sun, Y.: LSD1 destabilizes FBXW7 and inhibits FBXW7 activity independent of its demethylase activity. Proc Natl Acad Sci USA 2019 May 31. pii: 201902012. doi: 10.1073/pnas.1902012116.
  • Zhou, Q., Li, H., Li, Y., Tan, M., Fan, S., Cao, C., Meng, F., Zhu, L., Zhao, L., Guan, M.-X., Jin, H., and Sun, Y.: Inhibiting neddylation modification alters mitochondrial morphology and reprograms energy metabolism in cancer cells. JCI Insight. 2019 Jan 22. pii: 121582. doi: 10.1172/jci.insight.121582.
  • Xie, C., Tan, M., Lin, X., Wu, D., Jiang, Y., Tan, Y., Li, H., Ma, Y., Xiong, X., and Sun, Y.: The FBXW7-SHOC2-Raptor axis controls the cross-talks between the RAS/ERK and mTORC1 signaling pathways. Cell Reports. 2019;26(11):3037-3050.e4. doi: 10.1016/j.celrep.2019.02.052.
  • Zhou W, Xu J, Tan M, Zhang J, Li H, Li H, Wei W, and Sun, Y: UBE2M is a stress-inducible dual E2 for neddylation and ubiquitylation that promotes targeted degradation of UBE2F. Mol Cell 70: 1008–1024, 2018.
  • Xu J, Zhou W, Chen G, Li H, Zhao Y, Liu P, and Sun, Y: The βTrCP-FBXW2-SKP2 axis regulates lung cancer cell growth with FBXW2 acting as a novel tumor suppressor.  Nature Communs.  Jan 16; 8:14002. doi: 10.1038/ncomms14002, 2017.
  • Zhang Q, Karnak D, Tan M, Lawrence TS, Morgan MA, Sun Y: FBXW7 facilitates non-homologous end-joining via K63-linked polyubiquitylation of XRCC4. Mol Cell. 61: 419-433, 2016. (http://dx.doi.org/10.1016/j.molcel.2015.12.010).
  • Zhou, X. Tan, M., Nyati, M., Zhao, Y., Wang, G.X., and Sun, Y.: Blockage of neddylation modification stimulates tumor sphere formation in vitro, and stem cell differentiation and wound healing in vivo. Proc. Natl. Acad. Sci. USA. 2016 May 24;113(21): E2935-44. doi: 10.1073/pnas.1522367113. PMID:27162365.
  • Xie, C. M., Wei, D., Zhao, L., Marchetto, S., Mei, L., Borg, J.-P., and Sun, Y.: Erbin is a novel substrate of Sag-βTrCP E3 ligase that regulates KrasG12D-induced skin tumorigenesis. J. Cell Biol, 209: 721-737, 2015.
  • Li H, Tan M, Jia L, We, D, Zhao Y, Chen G, Xu J, Zhao L, Thomas D, Beer DG, and Sun Y: Inactivation of SAG/RBX2 E3 ubiquitin ligase suppresses KrasG12D-driven lung tumorigenesis.  J Clin Invest. 124:835-846, 2014.
  • Zhao, Y, Xiong, X, and Sun Y: DEPTOR, an mTOR inhibitor, is a physiological substrate of SCFβTrCPE3 ubiquitin ligase and regulates survival and autophagy. Mol Cell. 44: 304-316, 2011.
  • Tan M, Zhao Y, Kim S, Liu M, Jia L., Saunders T, Zhu Y, and Sun Y: SAG/RBX2/ROC2 E3 ubiquitin ligase is essential for vascular and neural development by targeting NF1 for degradation. Dev Cell. 21:1062-76, 2011. 

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