Department：Cancer Institute
Medical School：University of Iowa, USA
Academic Rank：Qiushi Chair Professor
Co-investigator on a Phase II clinical trial of pevonedistat plus docetaxel in patients with previously treated advanced non-small cell lung cancer.
Alice Hamilton Award for Scientific Excellence, National Institute for Occupational Safety and Health (NIOSH), 2000
Fellow, American Association for the Advancement of Science, 2012
Co-recipient of Dr. Clyde and Helen Wu Award in International Understanding by the Wu Family China Center for Health Initiatives at the Columbia University, Vagelos College of Physicians and Surgeons, 2018
Lawrence-Krause Research Professor in Radiation Oncology, University of Michigan, 2019
Qiushi Chair Professor, The Second Affiliated Hospital and Institute of Translational Medicine, Zhejiang University School of Medicine, China, 2020-present
Lawrence-Krause Research Professor in Radiation Oncology, 2019-2020
Director, Division of Radiation and Cancer Biology, Department of Radiation Oncology, University of Michigan, USA
Professor and Dean, Institute of Translational Medicine, Zhejiang University, China, 2014-2018
Professor with tenure, Radiation and Cancer Biology Division, Department of Radiation Oncology, University of Michigan, USA, 2008-2020
Director, Division of Radiation and Cancer Biology, Department of Radiation Oncology, University of Michigan, USA, 2008-2020
Associate Professor with tenure, Radiation and Cancer Biology Division, Department of Radiation Oncology, University of Michigan, USA, 2006-2008
Associate Professor, Radiation and Cancer Biology Division, Department of Radiation Oncology, University of Michigan, USA, 2003-2006
Research Fellow, Cancer Molecular Sciences, Pfizer Global Research & Development, Ann Arbor Laboratories, USA, 2002-2003
Associate Research Fellow, Department of Molecular Biology, Parke- Davis, Ann Arbor, MI and Cancer Molecular Sciences, Pfizer Global Research & Development, Ann Arbor Laboratories, USA, 1998-2002
Senior Research Associate, Department of Cancer Research, Parke-Davis, Ann Arbor, MI and Department of Molecular Biology, USA, 1995-1998
Senior Staff Fellow, Cell Biology Section, Laboratory of Viral Carcinogenesis, National Cancer Institute, USA, 1992-1994
Dr. Sun has broad research experience and expertise in cancer biology and mouse genetics. 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, his laboratory 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), -Catenin (Nat Commun. 2019), and MSX2 (PNAS, 2019b). His lab 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), in prostate tumorigenesis induced by Pten-loss (Mol Cancer, 2016), and in angiogenesis (Dev Cell, 2011, Oncogene 2014). Most recently, his lab 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 established himself as one of international leaders in the field of cullin-RING ligase and protein neddylation.
Areas of Interest
1) Cullin-RING ligase (CRL) and its RING component, SAG, in tumorigenesis and development of targeted cancer therapy
2) Protein neddylation in tumorigenesis and discovery of small molecule inhibitors for targeted cancer therapy.
Clinical Interest
Phase II clinical trials with MLN4924+Doceltaxol for the treatment of stage IV lung cancer.
Zhao Y*, Xiong X, Sun Y*. Cullin-RING Ligase 5: Functional Characterization and Its Role in Human Cancers. Semin Cancer Biol. 2020 Apr 22;S1044-579X(20)30085-7.
Qiao Y., Yang, F., Xie, T., Du, Z., Zhong, D., Qi, Y., Li, Y., Li, W., Lu, Z., Rao, J., Sun, Y.,* and Zhou, M.*. Engineered algae: a novel oxygen-generating system for effective cancer treatment. Science Advances 6: eaba5996 20 May 2020. (*Co-corresponding authors).
Yin Y, Xie CM, Li H, Tan M, Chen G, Schiff R, Xiong X, Sun Y*. The FBXW2-MSX2-SOX2 axis regulates stem cell property and drug resistance of cancer cells. Proc Natl Acad Sci U S A. 2019 Oct 8;116(41):20528-20538.
Mao H, Tang Z, Li H, Sun B, Tan M, Fan S, Zhu Y, Sun Y*. Neddylation inhibitor MLN4924 suppresses cilia formation by modulating AKT1. Protein Cell. 2019 Oct;10(10):726-744.
Lan H, Tan M, Li H, Xiong X, Sun, Y*. LSD1 destabilizes FBXW7 independent of its demethylase activity via promoting FBXW7 self-ubiquitylation for proteasomal and lysosomal degradation. Proc. Natl. Acad. Sci. USA. 2019 Jun 18;116(25):12311-12320.
Yang F, Xu J, Li H, Tan M, Xiong X, Sun Y*. FBXW2 suppresses migration and invasion of lung cancer cells via promoting ubiquitylation and degradation of β-catenin. Nature Communications. 2019 Mar 27;10(1):1382.
Xie CM, Tan M, Lin XT, Wu D, Jiang Y, Tan Y, Li H, Ma Y, Xiong X, Sun Y*. The FBXW7-SHOC2-Raptor axis controls the cross-talks between the RAS-ERK and mTORC1 signaling pathways. Cell Reports 2019 Mar 12;26(11):3037-3050.e4.
Zhou Q, Li H, Li Y, Tan M, Fan S, Cao C, Zhu L, Zhao L, Guan M-X, Jin H, Sun Y*. Inhibiting neddylation modification alters mitochondrial morphology and reprograms energy metabolism in cancer cells. JCI Insight. 2019 Feb 21;4(4). pii: 121582.
Zhang, Q., Mady, A.S.A., Ma, Y., Ryan, C., Lawrence, T.S., Nikolovska-Coleska, Z., Sun, Y.*, and Morgan, M.A.*: The WD40 domain of FBXW7 is a poly(ADP-ribose)-binding domain that mediates the early DNA damage response. Nucleic Acids Res. 2019 May 7, 47(8):4039-4053. (*Co-corresponding authors).
Zhou W, Xu J, Tan M, Zhang J, Li H, Li H, Wei W, Sun Y*. UBE2M is a stress-inducible dual E2 for neddylation and ubiquitylation that promotes targeted degradation of UBE2F. Mol Cell. 2018 Jun 21;70(6):1008-1024.e6.
Zhou, H., Lu, J., Liu L., Bernard, D., Yang, C.-Y., Chinnaswamy, K., Layton, S., Jeanne Stuckey, J., Yu, Q., Zhou, W., Pan, Z., Sun, Y., and Wang, S.: A potent small-molecule inhibitor of the DCN1-UBC12 interaction that selectively blocks cullin 3 neddylation. Nat Communs. 2017 Oct 27;8(1):1150.
Zhou W, Xu J, Li H, Xu M, Chen ZJ, Wei W, Pan Z, Sun Y*. Neddylation E2 UBE2F promotes the survival of lung cancer cells by activating CRL5 to degrade NOXA via the K11 linkage. Clinical Cancer Res. 2017 Feb 15;23(4):1104-1116.
Xu J, Zhou W, Yang F, Chen G, Li H, Zhao Y, Liu P, Li H, Tan M, Xiong X, Sun Y*. The β-TrCP-FBXW2-SKP2 axis regulates lung cancer cell growth with FBXW2 acting as a tumour suppressor. Nature Communications 2017 Jan 16; 8:14002.
Zhang Q, Karnak D, Tan M, Lawrence TS, Morgan MA, Sun Y*. FBXW7 facilitates nonhomologous end-joining via K63-linked polyubiquitylation of XRCC4. Mol. Cell, 2016(61): 419-433.
Zhou X, Tan M, Nyati M, Zhao Y, Wang GX, 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.
Role of Neddylation-Cullin RING ligases in lung inflammation-carcinoma transformation and to discover small molecule targeting inhibitors for lung cancer therapy. Funding Source: National Key R&D Program of China.
FBXW7-LSD1 non-degradable binding regulates DNA damage repair and lung tumorigenesis. Funding Source: National Natural Science Foundation of China.
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