Director and Principal Investigator, Interdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences (2020-present).

2014-2020, Elizabeth D. Hay Professor, Department of Cell Biology, Harvard Medical School

2000-2020, Professor, Department of Cell Biology, Harvard Medical School

1996-2000, Associate Professor, Department of Cell Biology, Harvard Medical School

1990-1996, Principal Investigator and Assistant Professor, Massachusetts General Hospital

1989, Ph.D. in Neuroscience, Harvard University

1982, B.S. in Biochemistry, Fudan University

The research of Professor Junying Yuan focuses on the molecular mechanisms that regulate cell death in health and diseases. Professor Yuan made ground-breaking discoveries on two major mechanisms of cell death, apoptosis and necroptosis. Her pioneering research has elucidated a series of key molecular mechanisms that control the regulation and execution of apoptosis and necroptosis and their involvement in major human diseases including neurodegeneration and cancer.

In 1990’s, Professor Yuan discovered the role of caspases in regulating apoptosis of mammalian cells as a highly evolutionarily conserved mechanism that controls apoptosis from primitive organisms to higher vertebrates and the role of Bcl-2 family in suppressing apoptosis mediated by caspases. She published a series of highly-cited classical papers including those that demonstrated the role of caspase-11 in regulating the activation of caspase-1 to mediate inflammation and the cleavage of BID by caspase-8 in mediating mitochondrial damage during apoptosis.

Since 2000, Professor Yuan began to investigate the possibility that necrosis may also be actively regulated in mammalian cells. Her research led to the discovery of necroptosis and demonstrated the role of RIPK1 as a critical mediator of necroptosis. Her discovery broke the traditional dogma that necrosis can only be passive cell death. Her research demonstrated the critical role of RIPK1 and necroptosis in mediating cell death and inflammation in major human neurodegenerative diseases including Alzheimer’s disease, amyotrophic lateral sclerosis, multiple sclerosis and stroke. RIPK1 inhibitors, first discovered by Professor Yuan, have been advanced into human clinical trials world-wide for the treatment of multiple neurodegenerative diseases.

The current research in Professor Yuan’s lab continues to elucidate the molecular mechanisms of cell death and their implications in human diseases.

Significant Works:

1. Miura M, Zhu H, Rotello R, Hartwieg EA, Yuan J. Induction of apoptosis in fibroblasts by IL-1 beta-converting enzyme, a mammalian homolog of the C. elegans cell death gene ced-3. Cell. 1993. 75(4):653-60. PMID: 8242741

2. Gagliardini V, Fernandez PA, Lee RK, Drexler HC, Rotello RJ, Fishman MC, Yuan J Prevention of vertebrate neuronal death by the crmA gene. Science. 1994. 263(5148):826-8. PMID: 8303301

3. Li H, Zhu H, Xu CJ, Yuan J. Cleavage of BID by caspase 8 mediates the mitochondrial damage in the Fas pathway of apoptosis. Cell. 1998. 94(4):491-501. PMID: 9727492 

4. Wang S, Miura M, Jung YK, Zhu H, Li E, Yuan J. Murine caspase-11, an ICE-interacting protease, is essential for the activation of ICE. Cell. 1998. 92(4):501-9. PMID: 9491891 

5. Degterev A, Huang Z, Boyce M, Li Y, Jagtap P, Mizushima N, Cuny GD, Mitchison TJ, Moskowitz MA, Yuan J. Chemical inhibitor of nonapoptotic cell death with therapeutic potential for ischemic brain injury. Nat Chem Biol. 1(2):112-9. PMID: 16408008.

6. Degterev A, Hitomi J, Germscheid M, Ch'en IL, Korkina O, Teng X, Abbott D, Cuny GD, Yuan C, Wagner G, Hedrick SM, Gerber SA, Lugovskoy A, Yuan J.  Identification of RIP1 kinase as a specific cellular target of necrostatins. Nat Chem Biol. 2008. 4(5):313-21. PMID: 18408713 

7. Hitomi J, Christofferson DE, Ng A, Yao J, Degterev A, Xavier RJ, Yuan J. Identification of a molecular signaling network that regulates a cellular necrotic cell death pathway. Cell. 2008. 135(7):1311-23. PMID: 19109899.

8. Ito Y, Ofengeim D, Najafov A, Das S, Saberi S, Li Y, Hitomi J, Zhu H, Chen H, Mayo L, Geng J, Amin P, DeWitt JP, Mookhtiar AK, Florez M, Ouchida AT, Fan JB, Pasparakis M, Kelliher MA, Ravits J, Yuan J. RIPK1 mediates axonal degeneration by promoting inflammation and necroptosis in ALS. Science. 2016. 353(6299):603-8. PMID: 27493188.

9. Xu D, Jin T, Zhu H, Chen H, Ofengeim D, Zou C, Mifflin L, Pan L, Amin P, Li W, Shan B, Naito MG, Meng H, Li Y, Pan H, Aron L, Adiconis X, Levin JZ, Yankner BA, Yuan J. TBK1 Suppresses RIPK1- Driven Apoptosis and Inflammation during Development and in Aging. Cell. 2018. 174(6):1477-1491. PMID: 30146158.

10. Xu D, Zhao H, Jin M, Zhu H, Shan B, Geng J, Dziedzic SA, Amin P, Mifflin L, Naito MG, Najafov A, Xing J, Yan L, Liu J, Qin Y, Hu X, Wang H, Zhang M, Manuel VJ, Tan L, He Z, Sun ZJ, Lee VMY, Wagner G, Yuan J. Modulating TRADD to restore cellular homeostasis and inhibit apoptosis. Nature. 2020. 587(7832):133-138. PMID: 32968279