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Junying Yuan

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The native form of this personal name is Yuan Junying. This article uses Western name order when mentioning individuals.
Junying Yuan
Born (1958-10-03) October 3, 1958 (age 66)
Shanghai, China
NationalityAmerican
Alma materFudan University
Harvard University
Massachusetts Institute of Technology
Known forApoptosis research
Necroptosis
Scientific career
FieldsBiology
Cell death
InstitutionsHarvard Medical School
Doctoral advisorH. Robert Horvitz

Junying Yuan (Chinese: 袁钧瑛; pinyin: Yuán Jūnyīng, born October 3, 1958) is the Elizabeth D. Hay Professor of Cell Biology at Harvard Medical School,[1] best known for her work in cell death. Early in her career, she contributed significant findings to the discovery and characterization of apoptosis.[2][3] More recently, she was responsible for the discovery of the programmed form of necrotic cell death known as necroptosis.[4]

Education and early career

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Yuan was born in Shanghai, her maternal grandfather was the scholar and translator Li Qingya (李青崖), and her paternal grandfather, Yuan Kaiji (袁开基), was a famous professor of organic chemistry. Her parents were both medical professors at Fudan University Shanghai Medical College, while her uncle, Yuan Chengye, was a professor and an academician of the Chinese Academy of Sciences. Junying Yuan attended Fudan University following the revival of higher education after its suspension under the Cultural Revolution. She was among the first wave of students to attempt the newly revived National Higher Education Entrance Examination in 1977, coming in first of all students who attempted it in Shanghai.[citation needed] She completed her bachelor's in biochemistry in 1982, and was subsequently one of the first students admitted to doctoral study in the United States through the China-U.S. Biochemistry Examination and Application (CUSBEA) program, coming in second out of the 25,000 who attempted the CUSBEA in its first year.[5]

In the United States, she completed her Ph.D. in Neuroscience(1989) at Harvard University under the supervision of MIT professor H. Robert Horvitz, where she endeavored to elucidate the molecular mechanisms behind programmed cell death in the nematode Caenorhabditis elegans. She identified the proteins ced-3 and ced-4 as drivers behind programmed cell death in C. elegans, and subsequently identified the mammalian homologue of ced-3 known as interleukin-1 beta-converting enzyme(ICE), later called caspase-1.[2][3][6]

Career

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Junying Yuan established an independent lab at Harvard-affiliated Massachusetts General Hospital in 1989, immediately upon completion of her Ph.D. [5] Her initial efforts were directed towards providing evidence for the functional role of caspases in mediating mammalian apoptosis.[7][8] Her independent work at this stage provided the first insights into molecular mechanisms in mammalian apoptosis, which contributed significantly to the Nobel Prize in Chemistry won by her Ph.D. supervisor, Robert Horvitz.[9]

In 1996, Yuan moved her lab to the Department of Cell Biology at Harvard Medical School's Longwood campus, where she continued her investigation into cell death. Her work delved further into programmed cell death and revealed a wide cohort of proteins involved in the regulation and consequences of apoptosis. Some notable work includes her discovery that BID cleavage by caspase-8 mediates mitochondrial damage in apoptosis,[10] and her discovery of caspase-11's role in regulating caspase-1-driven inflammation.[11]

In 2005, Yuan's group discovered a non-apoptotic form of programmed necrotic cell death, which they termed "necroptosis".[4] Other groups first observed that the stimulation of Fas/TNFR family of death-domain receptors (DR) activated a canonical apoptotic pathway; however, in many cell types, not only did caspase inhibition fail to inhibit cell death, as would be expected of canonical apoptosis, but stimulated cells experienced a form of cell death that more closely resembled necrosis than apoptosis.[12] Yuan's group conducted a chemical screen that identified a small molecule capable of inhibiting DR-driven cell death, necrostatin-1, and demonstrated necroptosis' role in ischemic neuronal injury, thereby positing a potential role for necrostatin-1 in stroke treatment. Her group then identified RIPK1 as the target for necrostatin-1,[13] thus implicating it as a key player in necroptosis.

Yuan went on to identify and characterize members of the signaling network responsible for regulating necroptosis,[14] and continues to elucidate the mechanisms of necroptosis while exploring its potential as a target of therapeutic intervention. Necrosis was previously considered to be a form of passive cell death, forced in response to stress. This belief had driven an aversion towards developing therapeutic applications targeting necrosis. In demonstrating a form of programmed necrosis, Yuan's work revealed new avenues of treatment for an ever-increasing cohort of diseases where necroptosis is implicated.[15] As of 2019, small-molecule inhibitors of RIPK1 have advanced beyond Phase I human clinical trials for the treatment of various inflammatory and neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS), Alzheimer's disease, rheumatoid arthritis, psoriasis, and Crohn's disease.[16]

Awards and Fellowships

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References

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  1. ^ "Yuan Named Hay Professor of Cell Biology". HMS News. Retrieved 13 May 2015.
  2. ^ a b Yuan, J. Y.; Horvitz, H. R. (1990). "The Caenorhabditis elegans genes ced-3 and ced-4 act cell autonomously to cause programmed cell death". Developmental Biology. 138 (1): 33–41. doi:10.1016/0012-1606(90)90174-h. PMID 2307287.
  3. ^ a b Yuan, J; Horvitz, H. R. (1992). "The Caenorhabditis elegans cell death gene ced-4 encodes a novel protein and is expressed during the period of extensive programmed cell death". Development. 116 (2): 309–20. doi:10.1242/dev.116.2.309. PMID 1286611.
  4. ^ a b Degterev, A; Huang, Z; Boyce, M; Li, Y; Jagtap, P; Mizushima, N; Cuny, G. D.; Mitchison, T. J.; Moskowitz, M. A.; Yuan, J (2005). "Chemical inhibitor of nonapoptotic cell death with therapeutic potential for ischemic brain injury". Nature Chemical Biology. 1 (2): 112–9. doi:10.1038/nchembio711. PMID 16408008. S2CID 866321.
  5. ^ a b "Junying Yuan" (PDF). ASCB Profile. Retrieved 13 May 2015.
  6. ^ Yuan, J; Shaham, S; Ledoux, S; Ellis, H. M.; Horvitz, H. R. (1993). "The C. Elegans cell death gene ced-3 encodes a protein similar to mammalian interleukin-1 beta-converting enzyme". Cell. 75 (4): 641–52. doi:10.1016/0092-8674(93)90485-9. PMID 8242740.
  7. ^ Miura, M; Zhu, H; Rotello, R; Hartwieg, E. A.; Yuan, J (1993). "Induction of apoptosis in fibroblasts by IL-1 beta-converting enzyme, a mammalian homolog of the C. Elegans cell death gene ced-3". Cell. 75 (4): 653–60. doi:10.1016/0092-8674(93)90486-a. PMID 8242741.
  8. ^ Gagliardini, V; Fernandez, P. A.; Lee, R. K.; Drexler, H. C.; Rotello, R. J.; Fishman, M. C.; Yuan, J (1994). "Prevention of vertebrate neuronal death by the crmA gene". Science. 263 (5148): 826–8. Bibcode:1994Sci...263..826G. doi:10.1126/science.8303301. PMID 8303301. S2CID 19330119.
  9. ^ "H. Robert Horvitz - Nobel Lecture: Worms, Life and Death" (PDF). Nobel Prize. Retrieved 14 May 2015.
  10. ^ Li, H; Zhu, H; Xu, C. J.; Yuan, J (1998). "Cleavage of BID by caspase 8 mediates the mitochondrial damage in the Fas pathway of apoptosis". Cell. 94 (4): 491–501. doi:10.1016/s0092-8674(00)81590-1. PMID 9727492.
  11. ^ Kang, S. J.; Wang, S; Hara, H; Peterson, E. P.; Namura, S; Amin-Hanjani, S; Huang, Z; Srinivasan, A; Tomaselli, K. J.; Thornberry, N. A.; Moskowitz, M. A.; Yuan, J (2000). "Dual role of caspase-11 in mediating activation of caspase-1 and caspase-3 under pathological conditions". The Journal of Cell Biology. 149 (3): 613–22. doi:10.1083/jcb.149.3.613. PMC 2174843. PMID 10791975.
  12. ^ Vercammen, D; Brouckaert, G; Denecker, G; Van De Craen, M; Declercq, W; Fiers, W; Vandenabeele, P (1998). "Dual signaling of the Fas receptor: Initiation of both apoptotic and necrotic cell death pathways". The Journal of Experimental Medicine. 188 (5): 919–30. doi:10.1084/jem.188.5.919. hdl:1854/LU-179898. PMC 2213397. PMID 9730893.
  13. ^ Degterev, A; Hitomi, J; Germscheid, M; Ch'En, I. L.; Korkina, O; Teng, X; Abbott, D; Cuny, G. D.; Yuan, C; Wagner, G; Hedrick, S. M.; Gerber, S. A.; Lugovskoy, A; Yuan, J (2008). "Identification of RIP1 kinase as a specific cellular target of necrostatins". Nature Chemical Biology. 4 (5): 313–21. doi:10.1038/nchembio.83. PMC 5434866. PMID 18408713.
  14. ^ Hitomi, J; Christofferson, D. E.; Ng, A; Yao, J; Degterev, A; Xavier, R. J.; Yuan, J (2008). "Identification of a molecular signaling network that regulates a cellular necrotic cell death pathway". Cell. 135 (7): 1311–23. doi:10.1016/j.cell.2008.10.044. PMC 2621059. PMID 19109899.
  15. ^ Zhou, W; Yuan, J (2014). "Necroptosis in health and diseases". Seminars in Cell & Developmental Biology. 35: 14–23. doi:10.1016/j.semcdb.2014.07.013. PMID 25087983.
  16. ^ Viegas, Jennifer (2019-06-11). "Profile of Junying Yuan". Proceedings of the National Academy of Sciences. 116 (24): 11564–11566. Bibcode:2019PNAS..11611564V. doi:10.1073/pnas.1906915116. ISSN 0027-8424. PMC 6575570. PMID 31110005.
  17. ^ "Fellows of the Foundation". Albert J. Ryan Foundation. Retrieved 13 May 2015.
  18. ^ "Wilson S. Stone Memorial Award Recipients" (PDF). Archived from the original (PDF) on 10 September 2015. Retrieved 13 May 2015.
  19. ^ a b c d "Junying Yuan - Curriculum Vitae". Archived from the original on 2016-03-04. Retrieved 2015-05-16.
  20. ^ "Innovator Award Recipients from the DOD Breast Cancer Research Program". U.S. Army Medical Research and Materiel Command. Archived from the original on 9 October 2013. Retrieved 13 May 2015.
  21. ^ "Awardees". celldeath-apoptosis.org (ICDS). Archived from the original on 25 February 2015. Retrieved 13 May 2015.
  22. ^ "Junying Yuan". American Academy of Arts and Sciences. Retrieved 14 May 2015.[permanent dead link]
  23. ^ "AAAS Members Elected as Fellows". American Association for the Advancement of Science. Retrieved 14 May 2015.
  24. ^ "Agilent Technologies Thought Leader Award Supports Dr. Junying Yuan, Chinese Academy of Sciences". Agilent Technologies. Retrieved 13 May 2015.[permanent dead link]
  25. ^ "May 2, 2017: NAS Members and Foreign Associates Elected".
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