Xiaodong Wang
王晓东
Born1963 (age 60–61)
Wuhan, Hubei
China[1]
NationalityAmerican[2]
EducationBeijing Normal University (BSc)
University of Texas Southwestern Medical Center (PhD)
AwardsEli Lilly Award in Biological Chemistry
NAS Award in Molecular Biology
Shaw Prize in Life Science and Medicine
Richard Lounsbery Award
King Faisal International Prize in Medicine
Xiaodong Wang
Known forResearch of programmed cell death by apoptosis and necroptosis
Scientific career
FieldsBiochemistry
InstitutionsEmory University
University of Texas Southwestern Medical Center
Howard Hughes Medical Institute
National Institute of Biological Sciences, Beijing
BeiGene
ThesisStudies on the process of mammalian precursor messenger RNA splice site selection (1991)
Doctoral advisorRichard A. Padgett
Xiaodong Wang
Traditional Chinese王曉東
Simplified Chinese王晓东

Xiaodong Wang (born 1963) is a Chinese-American biochemist best known for his work with apoptosis, one of the ways through which cells kill themselves.

Early life and education

Wang was born in Wuhan, China in 1963, and was raised in Xinxiang, Henan by his grandparents. His family was relatively well-educated. His grandfather was a high school English teacher, his grandmother a primary school teacher, and his great uncle a biology professor. His primary and secondary coincided with the Cultural Revolution, and he only started high school in 1978 at a top high school in Henan.[1][3]

He entered the Beijing Normal University in 1980,[1] majoring in biology, and completed 4 years later.[4] His undergraduate thesis supervisor, Shaobai Xue, introduced him to cell biology and biochemistry, and prompted him to pursue postgraduate studies in biochemistry.[1]

Through the government-sponsored Chinese-US Biochemistry Examination and Application (CUSBEA) program, the biochemistry counterpart to CUSPEA, Wang went to the University of Texas Southwestern Medical Center in 1985 for his PhD.[1] The CUSBEA program was initiated by the biochemist Ray Wu at Cornell University and lasted from 1982 to 1989.[5][6] He graduated in 1991.[4]

Career

After obtaining his PhD, Wang moved to the research group of Joseph L. Goldstein and Michael Stuart Brown, also at the University of Texas Southwestern Medical Center (UTSW) as a postdoctoral fellow. He joined the Department of Biochemistry of Emory University in 1995 as an assistant professor, then returned to UTSW a year later as an assistant professor at its Department of Biochemistry. He was promoted to associate professor in 1999.[4] In 2001, Wang was appointed the George L. MacGregor Distinguished Chair in Biomedical Sciences.[7]

Wang became an investigator at the Howard Hughes Medical Institute in 1997.[8]

Since 2003, Wang has been an investigator at the National Institute of Biological Sciences, Beijing (NIBS). In 2010, he ended all his positions in the United States and returned to China to take up the role of director of NIBS.[7]

Wang co-founded two biotechnology companies: Joyant Pharmaceuticals in 2004 and BeiGene in 2010.[9] He currently chairs the Scientific Advisory Board of BeiGene.[10]

Wang chaired the Science Committee of the Future Science Prize in 2017, and currently sits on the committee.[11]

Research

Wang's research on apoptosis began accidentally when he was a postdoctoral fellow at the research group of Joseph L. Goldstein and Michael Stuart Brown at the University of Texas Southwestern Medical Center. Apoptosis is a form of programmed cell death, which is the mechanisms that cells use kill themselves. Brown and Goldstein were at the time studying the transcriptional regulation of the low-density lipoprotein (LDL) receptor in response to cholesterol level. One of the regulatory mechanisms was through the activation of SREBP, a protein that regulates the manufacturing of mRNA from genes coding for proteins that import and synthesize cholesterol. SREBP bound to nuclear envelope and endoplasmic reticulum membranes, and had to be cleaved to be activated.[12]

In 1995, Wang reported a protein in hamsters believed to be the one that cleaved SREBP. However, he also found that the human counterpart of this hamster protein was CPP32, which itself was related to one of the first proteins shown to be involved in initiating apoptosis.[13] The CPP32 protein was officially renamed caspase 3 the following year.[14]

Breakthrough came during Wang's one year at Emory University, when he developed a cell-free, in vitro system that replicated the activation of caspase 3 and the initiation of apoptosis.[3] Using this system, his group characterized the proteins required for starting apoptosis, including cytochrome c,[15] Bcl-2,[16] APAF1,[17] and pro-caspase-9.[18]

In 1997, his group reported the activation steps of apoptosis: Bcl-2 regulates the release of cytochrome c from the mitochondria to the cytosol, then cytochrome c binds to APAF1 and forms a protein complex called the apoptosome. The apoptosome recruits and cleaves procaspase-9 to the active form caspase-9, which in turn cleaves procaspase-3 to the active caspase 3.[18]

Apart from apoptosis, Wang also discovered the necroptosis pathway, which is the programmed form of necrosis and another way that a cell kills itself. He established the role of RIPK3 and the MLKL protein in necroptosis.[19]

Honors and awards

References

  1. 1 2 3 4 5 "Autobiography of Xiaodong Wang". Shaw Prize. Archived from the original on October 19, 2023. Retrieved October 19, 2023.
  2. ↑ "王晓东（Xiaodong Wang）" (in Chinese). Chinese Academy of Sciences. Archived from the original on October 17, 2023. Retrieved October 17, 2023.
  3. 1 2 Zagorski, Nick (2006). "Profile of Xiaodong Wang". Proceedings of the National Academy of Sciences of the United States of America. 103 (1): 7–9. doi:10.1073/pnas.0509187103. PMC 1324996. PMID 16380419. Archived from the original on October 27, 2023. Retrieved October 27, 2023.
  4. 1 2 3 "王晓东博士" (in Chinese). National Institute of Biological Sciences, Beijing. Archived from the original on October 19, 2023. Retrieved October 19, 2023.
  5. ↑ Chang, Zengyi (2009). "The CUSBEA program: Twenty years after". IUBMB Life. 61 (6): 555–565. doi:10.1002/iub.218. PMID 19472190. Archived from the original on October 19, 2023. Retrieved October 19, 2023.
  6. ↑ Gu, Xiaocheng (2009). "Ray Wu and the CUSBEA Program". Science in China Series C: Life Sciences. 52 (2): 125–127. doi:10.1007/s11427-009-0020-9. PMID 19277521. Retrieved October 19, 2023.
  7. 1 2 "DIRECTORS AND SENIOR MANAGEMENT". BeiGene, Ltd. Global Offering Prospectus (PDF). BeiGene. July 30, 2018. p. 323. Archived from the original (PDF) on October 20, 2023. Retrieved October 20, 2023.
  8. ↑ "Xiaodong Wang, PhD". Howard Hughes Medical Institute. Archived from the original on October 20, 2023. Retrieved October 20, 2023.
  9. ↑ "BeiGene". Forbes. Archived from the original on October 21, 2023. Retrieved October 21, 2023.
  10. ↑ "Xiaodong Wang, Ph.D." BeiGene. Archived from the original on October 18, 2023. Retrieved October 18, 2023.
  11. ↑ "Xiaodong WANG". Future Science Prize. Archived from the original on October 31, 2023. Retrieved October 31, 2023.
  12. ↑ "SREBPs: activators of the complete program of cholesterol and fatty acid synthesis in the liver". Journal of Clinical Investigation. 109 (9): 1125–1131. 2002. doi:10.1172/JCI15593. PMC 150968. PMID 11994399. Archived from the original on October 25, 2023. Retrieved October 25, 2023.
  13. ↑ Wang, Xiaodong; Pai, Jih-tung; Wiedenfeld, Elizabeth A.; Medina, Julio C.; Slaughter, Clive A.; Goldstein, Joseph L.; Brown, Michael S. (1995). "Purification of an Interleukin-1β Converting Enzyme-related Cysteine Protease That Cleaves Sterol Regulatory Element-binding Proteins between the Leucine Zipper and Transmembrane Domains". Journal of Biological Chemistry. 270 (30): 18044–18050. doi:10.1074/jbc.270.30.18044. PMID 7629113. Archived from the original on October 27, 2023. Retrieved October 27, 2023.
  14. ↑ Alnemri, Emad S.; Livingston, David J.; Nicholson, Donald W.; Salvesen, Guy; Thornberry, Nancy A.; Wong, Winnie W.; Yuan, Junying (1996). "Human ICE/CED-3 Protease Nomenclature". Cell. 87 (2): 171. doi:10.1016/s0092-8674(00)81334-3. PMID 8861900. Retrieved October 27, 2023.
  15. ↑ Liu, Xuesong; Kim, Caryn Naekyung; Yang, Jie; Jemmerson, Ronald; Wang, Xiaodong (1996). "Induction of Apoptotic Program in Cell-Free Extracts: Requirement for dATP and Cytochrome c". Cell. 86 (1): 147–157. doi:10.1016/s0092-8674(00)80085-9. PMID 8689682. Archived from the original on October 30, 2023. Retrieved October 30, 2023.
  16. ↑ Yang, Jie; Liu, Xuesong; Bhalla, Kapil; Kim, Caryn Naekyung; Ibrado, Ana Maria; Cai, Jiyang; Peng, Tsung-I; Jones, Dean P.; Wang, Xiaodong (1997). "Prevention of Apoptosis by Bcl-2: Release of Cytochrome c from Mitochondria Blocked". Science. 275 (5303): 1129–1132. doi:10.1126/science.275.5303.1129. PMID 9027314. Retrieved October 30, 2023.
  17. ↑ Zou, Hua; Henzel, William J.; Liu, Xuesong; Lutschg, Alexis; Wang, Xiaodong (1997). "Apaf-1, a human protein homologous to C. elegans CED-4, participates in cytochrome c-dependent activation of caspase-3". Cell. 90 (3): 405–413. doi:10.1016/s0092-8674(00)80501-2. ISSN 0092-8674. PMID 9267021. S2CID 18105320. Archived from the original on October 30, 2023.
  18. 1 2 Li, Peng; Nijhawan, Deepak; Budihardjo, Imawati; Srinivasula, Srinivasa M.; Ahmad, Manzoor; Alnemri, Emad S.; Wang, Xiaodong (1997). "Cytochrome c and dATP-Dependent Formation of Apaf-1/Caspase-9 Complex Initiates an Apoptotic Protease Cascade". Cell. 91 (4): 479–489. doi:10.1016/s0092-8674(00)80434-1. PMID 9390557. Archived from the original on October 30, 2023. Retrieved October 30, 2023.
  19. ↑ Sun, Liming; Wang, Huayi; Wang, Zhigao; He, Sudan; Chen, She; Liao, Daohong; Wang, Lai; Yan, Jiacong; Liu, Weilong; Lei, Xiaoguang; Wang, Xiaodong (2012). "Mixed Lineage Kinase Domain-like Protein Mediates Necrosis Signaling Downstream of RIP3 Kinase". Cell. 148 (1–2): 213–227. doi:10.1016/j.cell.2011.11.031. PMID 22265413. Archived from the original on October 31, 2023. Retrieved October 31, 2023.
  20. ↑ "Eli Lilly Award in Biological Chemistry" (PDF). Division of Biological Chemistry, American Chemical Society. Archived from the original (PDF) on October 21, 2023. Retrieved October 21, 2023.
  21. ↑ "Xiaodong Wang". National Academy of Sciences. Archived from the original on October 24, 2023. Retrieved October 24, 2023.
  22. ↑ "NAS Award in Molecular Biology". National Academy of Sciences. Archived from the original on October 21, 2023. Retrieved October 21, 2023.
  23. ↑ "Richard Lounsbery Award". National Academy of Sciences. Archived from the original on October 21, 2023. Retrieved October 21, 2023.
  24. ↑ "Life Science & Medicine 2006". Shaw Prize. Archived from the original on October 20, 2023. Retrieved October 20, 2023.
  25. ↑ Hunt, Geoff (February 23, 2012). "Wang lauded as 'one of the most highly original, bold and creative scientists'". Archived from the original on October 25, 2023. Retrieved October 25, 2023.
  26. ↑ "关于公布2013年中国科学院院士增选和外籍院士选举结果的公告" (in Chinese). Chinese Academy of Sciences. December 19, 2013. Archived from the original on October 21, 2023. Retrieved October 21, 2023.
  27. ↑ "Xiaodong Wang". European Molecular Biology Organization. Archived from the original on October 18, 2023. Retrieved October 18, 2023.
  28. ↑ "Professor Xiaodong Wang". King Faisal Prize. Archived from the original on October 25, 2023. Retrieved October 25, 2023.
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