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Yi Sun (academic)

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Yi Sun
NationalityAmerican
Occupation(s)Biologist, Oncologist
Academic background
EducationM.D.
M.S. I. Biochemistry
Ph.D. in Radiation biology
Alma materJiangxi Medical College
Zhejiang University School of Medicine
University of Iowa
Academic work
InstitutionsInstitute of Translational Medicine of Zhejiang University

Yi Sun (Chinese: 孙毅) is an American scientist of Chinese origin. He is a molecular biologist and oncologist, and his research is focused on how altered protein Ubiquitylation and Neddylation contribute to cancer development. Sun is a Professor Emeritus of Radiation Oncology at the University of Michigan.[1]

Sun is the Qiushi Chair Professor at the second Affiliated Hospital and Institute of Translational Medicine, Zhejiang University School of Medicine in China.[2] He has published over 290 papers in peer-reviewed journals with an H-index of 78 and over 39,000 citations.[3] Sun has been a fellow of the American Association for the Advancement of Science since 2012.[4][5]

Career and education

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In 1982, Sun obtained his M.D. degree at Jiangxi Medical College, Nanchang, China, and continued to Zhejiang University's School of Medicine, where he had his M.S. in biochemistry in 1985.[6] He moved to the United States in 1986 and obtained his PhD in Radiation biology from the University of Iowa in 1989. Sun spent five years at the National Cancer Institute as a post doctoral fellow, later as a senior staff fellow from 1990 to 1995.[6]

Sun then spent 8 years in Parke-Davis/Pfizer as research fellow for cancer target identification and drug discovery in Ann Arbor, Michigan.[1][6] He then joined the faculty of University of Michigan in 2003, and was promoted to full-time professor and Director of the Division of Radiation and Cancer Biology in 2008.[1]

Sun retired in 2020.[1]

Research

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Sun has research expertise in cancer biology, radiation oncology, and translational medicine, specialized in protein ubiquitylation and neddylation, and their role in cancer.

SAG/RBX2 E3 ligase is a validated anti-cancer target

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Sun cloned SAG (Sensitive to Apoptosis Gene), also known as RBX2, as an antioxidant protein, and a RING component of Cullin-RING ubiquitin ligases (CRLs), required for their activities; He and his team discovered that Sag is essential for mouse development, as well as for angiogenesis and apoptosis protection. The team validated SAG as a target for anti-cancer drug discovery by demonstrating its promoting role during tumorigenesis in the lung, prostate, and pancreas; and its overexpression in human cancer tissues with positive correlation to poor survival of cancer patients.[7]

SAG-CRLs regulates many important biological processes via targeting degradation of key proteins

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Sun and his team identified a number of key regulatory proteins as the substrates of CRLs that control a variety of important signal pathways and biological processes, particularly in growth and survival of cancer cells. These substrates include DEPTOR, XRCC4, SHOC2, SKP2, β-Catenin, MSX2, Nf1, c-Jun, IκBα, Erbin, NOXA, ASCT2, and DIRAS-2, as well as procaspase-3, HIF-1α, p27, MFN1, and EGR1. Targeted inhibition of CRLs causes accumulation of the tumor suppressors to inhibit cancer cell growth and cancer development.[8][9][10]

Elucide neddylation function and discover neddylation inhibitors as novel anticancer agents

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Sun and his team showed a cross-talk between two neddylation E2s, and neddylation E2/E3 regulated the functions of immune cells. The team also found that E1 inhibitor MLN4924 sensitizes pancreatic cancer cells to radiation; regulates stem cell proliferation and differentiation; and strikingly suppressed tumorigenesis in the lung and pancreas, triggered by mutant KrasG12D as a single agent. The study in the lung tumorigenesis triggered an intensive collaboration with Takeda Pharmaceutics, Inc., leading to an investigator-initiated Phase II clinical trials of MLN4924 (also known as pevonedistat) plus Docetaxel in patients with previously treated advanced non-small cell lung cancer. In drug discovery side, Sun and his collaborators discovered small molecule inhibitors of neddylation E1, neddylation E2 UBE2F and UBE2M-DCN interactions.[11]

Selected publications

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Tan, M., Zhao, Y., Kim, S. J., Liu, M., Jia, L., Saunders, T. L., Zhu, Y., & Sun, Y. (2011). SAG/RBX2/ROC2 E3 ubiquitin ligase is essential for vascular and neural development by targeting NF1 for degradation. Developmental cell, 21(6), 1062–1076. https://doi.org/10.1016/j.devcel.2011.09.014

Zhao, Y., Xiong, X., & Sun, Y. (2020). Cullin-RING Ligase 5: Functional characterization and its role in human cancers. Seminars in cancer biology, 67(Pt 2), 61–79. https://doi.org/10.1016/j.semcancer.2020.04.003

Li, H., Tan, M., Jia, L., Wei, D., Zhao, Y., Chen, G., Xu, J., Zhao, L., Thomas, D., Beer, D. G., & Sun, Y. (2014). Inactivation of SAG/RBX2 E3 ubiquitin ligase suppresses KrasG12D-driven lung tumorigenesis. The Journal of clinical investigation, 124(2), 835–846. https://doi.org/10.1172/JCI70297

Zhao, Y., Xiong, X., & Sun, Y. (2011). DEPTOR, an mTOR inhibitor, is a physiological substrate of SCF(βTrCP) E3 ubiquitin ligase and regulates survival and autophagy. Molecular cell, 44(2), 304–316. https://doi.org/10.1016/j.molcel.2011.08.029

Zhang, Q., Karnak, D., Tan, M., Lawrence, T. S., Morgan, M. A., & Sun, Y. (2016). FBXW7 Facilitates Nonhomologous End-Joining via K63-Linked Polyubiquitylation of XRCC4. Molecular cell, 61(3), 419–433. https://doi.org/10.1016/j.molcel.2015.12.010

Zhou, W., Xu, J., Tan, M., Li, H., Li, H., Wei, W., & Sun, Y. (2018). UBE2M Is a Stress-Inducible Dual E2 for Neddylation and Ubiquitylation that Promotes Targeted Degradation of UBE2F. Molecular cell, 70(6), 1008–1024.e6. https://doi.org/10.1016/j.molcel.2018.06.002

Zhang, S., You, X., Zheng, Y., Shen, Y., Xiong, X., & Sun, Y. (2023). The UBE2C/CDH1/DEPTOR axis is an oncogene and tumor suppressor cascade in lung cancer cells. The Journal of clinical investigation, 133(4), e162434. https://doi.org/10.1172/JCI162434

References

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  1. ^ a b c d "The Regents of the University of Michigan" (PDF). University of Michigan.
  2. ^ "Yi Sun-Zhejiang University Personal homepage". person.zju.edu.cn.
  3. ^ "Yi Sun". scholar.google.com.
  4. ^ "Historic Fellows | American Association for the Advancement of Science". www.aaas.org.
  5. ^ "U-M leads nation with 19 AAAS fellows". umich.edu. 29 November 2012.
  6. ^ a b c "Sun Yi" (PDF). Retrieved June 4, 2024.
  7. ^ "Yi Sun". Research.com.
  8. ^ Zhou, Q.; Lin, W.; Wang, C.; Sun, F.; Ju, S.; Chen, Q.; Wang, Y.; Chen, Y.; Li, H.; Wang, L.; Hu, Z.; Jin, H.; Wang, X.; Sun, Y. (2022). "Neddylation inhibition induces glutamine uptake and metabolism by targeting CRL3SPOP E3 ligase in cancer cells". Nature Communications. 13 (1): 3034. doi:10.1038/s41467-022-30559-2. PMC 9156729. PMID 35641493.
  9. ^ Chang, Y.; Chen, Q.; Li, H.; Xu, J.; Tan, M.; Xiong, X.; Sun, Y. (2024). "The UBE2F-CRL5ASB11-DIRAS2 axis is an oncogene and tumor suppressor cascade in pancreatic cancer cells". Developmental Cell. 59 (10): 1317–1332.e5. doi:10.1016/j.devcel.2024.03.018. PMID 38574733.
  10. ^ Sun, Y.; Li, H. (2013). "Functional characterization of SAG/RBX2/ROC2/RNF7, an antioxidant protein and an E3 ubiquitin ligase". Protein & Cell. 4 (2): 103–116. doi:10.1007/s13238-012-2105-7. PMC 3888511. PMID 23136067.
  11. ^ Zhang, S.; Yu, Q.; Li, Z.; Zhao, Y.; Sun, Y. (2024). "Protein neddylation and its role in health and diseases". Signal Transduction and Targeted Therapy. 9 (1): 85. doi:10.1038/s41392-024-01800-9. PMC 10995212. PMID 38575611.
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