General
SUN Liming
Ph.D., Professor
Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yue-yang Road, Shanghai 200031, China.
Email: liming.sun@sibcb.ac.cn
Research Areas
Cell death plays pivotal roles in many biological processes, such as development and pathogenesis of many degenerative diseases. Programmed necrosis, also known as necroptosis, is morphologically marked by the swelling of cellular organelles, rapid loss of cell membrane integrity and release of cellular contents. Necrosis functions during pathogen infection, drug-induced cell injuries and trauma-induced tissue damages. The necrotic death of injured cells help to isolate and remove the pathogens and induce immune response to viral infection. In addition, necrosis is implicated in regulating chemical-induced cell injuries, such as cerulein-induced pancreatitis. Furthermore, excessive necrotic cell death is associated with ischemia reperfusion induced damage in brain and cardiac tissues as well as in patients with neurodegenerative disorders. On the other hand, dysfunction of apoptosis underlies tumor genesis, proliferation and resistance to chemotherapy. As the alternative cell death, necrosis induced by various therapeutic stimuli will provide us a new direction in the treatment of cancer.
Programmed necrosis is a kinase initiated death pathway. In the case of TNFR1 activation, the most studied model of necrosis to date, the necrotic cell death depends on the kinase activity of RIP1 and RIP3. Mixed lineage kinase domain-like protein (MLKL) is a critical substrate of RIP3 in necrosis pathway. The formation of necrosome by the interaction of RIP1, RIP3, MLKL and other molecules would mediate the signaling downstream of death cytokines (such as TNF), finally causing cell death and inflammation.
Our research focuses on the molecular mechanism of necrosis signaling, and the relevance to human diseases. We sincerely welcome those who are interested in cell death to join us!
Programmed necrosis is a kinase initiated death pathway. In the case of TNFR1 activation, the most studied model of necrosis to date, the necrotic cell death depends on the kinase activity of RIP1 and RIP3. Mixed lineage kinase domain-like protein (MLKL) is a critical substrate of RIP3 in necrosis pathway. The formation of necrosome by the interaction of RIP1, RIP3, MLKL and other molecules would mediate the signaling downstream of death cytokines (such as TNF), finally causing cell death and inflammation.
Our research focuses on the molecular mechanism of necrosis signaling, and the relevance to human diseases. We sincerely welcome those who are interested in cell death to join us!
Publications
Selected Publications
- Zhang J, Yang Y, He W, and Sun L*. Necrosome core machinery: MLKL. Cellular and Molecular Life Sciences, 2016,73, 2153-2163.
(*Corresponding author) - Sun L.* and Wang X. A new kind of cell suicide: mechanisms and functions of programmed necrosis. Trends in biochemical sciences, 2014, 39, 587-593
(*Corresponding author) - Su L, Quade B, Wang H, Sun L, Wang X, and Rizo J. (2014) A Plug Release Mechanism for Membrane Permeation by MLKL. Structure, 2014, 22(10): 1489-1500
- Wang H, Sun L, Su L, Rizo J, Liu L, Wang LF, Wang FS, and Wang X. Mixed Lineage Kinase Domain-like protein MLKL Causes Necrotic Membrane Disruption Upon Phosphorylation by RIP3. Mol Cell, 2014, 54, 133-146.
*Cover story. Story of this work was selected by Faculty of 1000 Biology - Sun L, Wang H, Wang Z, He S, Chen S, Liao D, Wang L, Yan J, Liu W, Lei X, and Wang X. Mixed lineage kinase domain-like protein mediates necrosis signaling downstream of RIP3 kinase. Cell, 2012, 148, 213-227.
*Research of this work was highlighted in Cell, Nature Reviews Molecular Cell Biology, and Chem. & Eng. News. Story of this work was selected by Faculty of 1000 Biology. - Liao D, Sun L, Liu W, He S, Wang X, and Lei X. Necrosulfonamide Inhibits Necroptosis by Selectively Targeting the Mixed Lineage Kinase Domain-like Protein. Med. Chem. Commun., 2014, 5, 333-337.
- Li S, Zhang L, Yao Q, Li L, Dong N, Rong J, Gao W, Ding X, Sun L, Chen X, Chen S, Shao F. Pathogen blocks host death receptor signalling by arginine GlcNAcylation of death domains. Nature, 2013, 501, 242-6.
- Hildebrand JM, Sun L, and Silke J. An appointment with death,生死有时: 2013 Cold Spring Harbor Asia meeting ‘Mechanisms and Functions of Non- Apoptotic Cell Death’. Cell Death Differ, 2013, 20, 1593-4.
- Sun L, Wang H, Hu J, Han J, Matsunami H, and Luo M. Guanylyl cyclase-D in the olfactory CO2 neurons is activated by bicarbonate. Proc Natl Acad Sci U S A, 2009, 106, 2041-2046.
- Luo M, Sun L, and Hu J. Neural detection of gases--carbon dioxide, oxygen--in vertebrates and invertebrates. Curr Opin Neurobiol, 2009, 19, 354-361.