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, and was endowed as Lawrence-Krause Research Professor in Radiation Oncology in 2019. 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), stem cell property and drug resistance (PNAS 2019b); 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, 2019a).
Dr. Sun has published 228 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.
- 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.
Selected from 228 publications
- The FBXW2-MSX2-SOX2 axis regulates stem cell property and drug resistance of cancer cells. Yin Y, Xie CM, Li H, Tan M, Chen G, Schiff R, Xiong X, Sun Y. Proc Natl Acad Sci U S A. 2019 Oct 8;116(41):20528-20538. doi: 10.1073/pnas.1905973116. Epub 2019 Sep 23. PMID: 31548378 PMCID: PMC6789910 [Available on 2020-03-23] DOI: 10.1073/pnas.1905973116
- LSD1 destabilizes FBXW7 and abrogates FBXW7 functions independent of its demethylase activity. Lan H, Tan M, Zhang Q, Yang F, Wang S, Li H, Xiong X, Sun Y. Proc Natl Acad Sci U S A. 2019 Jun 18;116(25):12311-12320. doi: 10.1073/pnas.1902012116. Epub 2019 May 31. PMID: 31152129 PMCID: PMC6589684 DOI: 10.1073/pnas.1902012116
- The WD40 domain of FBXW7 is a poly(ADP-ribose)-binding domain that mediates the early DNA damage response. Zhang Q, Mady ASA, Ma Y, Ryan C, Lawrence TS, Nikolovska-Coleska Z, Sun Y, Morgan MA. Nucleic acids research. 2019; 47(8):4039-4053.
- FBXW2 suppresses migration and invasion of lung cancer cells via promoting β-catenin ubiquitylation and degradation. Yang F, Xu J, Li H, Tan M, Xiong X, Sun Y. Nature communications. 2019; 10(1):1382.
- The FBXW7-SHOC2-Raptor Axis Controls the Cross-Talks between the RAS-ERK and mTORC1 Signaling Pathways. Xie CM, Tan M, Lin XT, Wu D, Jiang Y, Tan Y, Li H, Ma Y, Xiong X, Sun Y. Cell reports. 2019; 26(11):3037-3050.e4. NIHMSID: NIHMS1026656
- Inhibiting neddylation modification alters mitochondrial morphology and reprograms energy metabolism in cancer cells. Zhou Q, Li H, Li Y, Tan M, Fan S, Cao C, Meng F, Zhu L, Zhao L, Guan MX, Jin H, Sun Y. JCI insight. 2019; 4(4).
- UBE2M Is a Stress-Inducible Dual E2 for Neddylation and Ubiquitylation that Promotes Targeted Degradation of UBE2F. Zhou W, Xu J, Tan M, Li H, Li H, Wei W, Sun Y. Molecular cell. 2018; 70(6):1008-1024.e6. NIHMSID: NIHMS974123
- The β-TrCP-FBXW2-SKP2 axis regulates lung cancer cell growth with FBXW2 acting as a tumour suppressor. Xu J, Zhou W, Yang F, Chen G, Li H, Zhao Y, Liu P, Li H, Tan M, Xiong X, Sun Y. Nature communications. 2017; 8:14002. PubMed [journal] PMID: 28090088 PMCID: PMC5241824
- FBXW7 Facilitates Nonhomologous End-Joining via K63-Linked Polyubiquitylation of XRCC4. Zhang Q, Karnak D, Tan M, Lawrence TS, Morgan MA, Sun Y. Molecular cell. 2016; 61(3):419-433. NIHMSID: NIHMS745172 PubMed [journal] PMID: 26774286 PMCID: PMC4744117
- Blockage of neddylation modification stimulates tumor sphere formation in vitro and stem cell differentiation and wound healing in vivo. Zhou X, Tan M, Nyati MK, Zhao Y, Wang G, Sun Y. Proceedings of the National Academy of Sciences of the United States of America. 2016; 113(21):E2935-44. PubMed [journal] PMID: 27162365 PMCID: PMC4889367
Erbin is a novel substrate of the Sag-βTrCP E3 ligase that regulates KrasG12D-induced skin tumorigenesis. Xie CM, Wei D, Zhao L, Marchetto S, Mei L, Borg JP, Sun Y. The Journal of cell biology. 2015; 209(5):721-37.
PubMed journal] PMID: 26056141 PMCID: PMC4460146
- Inactivation of SAG/RBX2 E3 ubiquitin ligase suppresses KrasG12D-driven lung tumorigenesis. Li H, Tan M, Jia L, Wei D, Zhao Y, Chen G, Xu J, Zhao L, Thomas D, Beer DG, Sun Y. The Journal of clinical investigation. 2014; 124(2):835-46. PubMed [journal] PMID: 24430184 PMCID: PMC3904615
- DEPTOR, an mTOR inhibitor, is a physiological substrate of SCF(βTrCP) E3 ubiquitin ligase and regulates survival and autophagy. Zhao Y, Xiong X, Sun Y. Molecular cell. 2011; 44(2):304-16. NIHMSID: NIHMS328094 PubMed [journal] PMID: 22017876 PMCID: PMC3216641
- SAG/RBX2/ROC2 E3 ubiquitin ligase is essential for vascular and neural development by targeting NF1 for degradation. Tan M, Zhao Y, Kim SJ, Liu M, Jia L, Saunders TL, Zhu Y, Sun Y. Developmental cell. 2011; 21(6):1062-76. NIHMSID: NIHMS328990 PubMed [journal] PMID: 22118770 PMCID: PMC3241850