Research Summary
Listeria monocytogenes is the causative agent of listeriosis, a bacterial infection that can cause severe illness, including septicaemia via blood infection, meningitis and encephalitis in the brain, and perinatal infection or abortion via placenta. Thus, it is a big threat to the elderly, pregnant women, fetuses, newborns, and those who are immunocompromised. It may also cause mild, self-limiting gastroenteritis and fever in immunocompetent people. Listeria contamination is a big danger for the food industry since the main route of acquisition of Listeria is through the ingestion of contaminated food products.
Listeria monocytogenes is a facultative anaerobic foodborne bacterium. As a Gram-positive intracellular pathogen, it can grow and reproduce inside the host’s cells. Normally, Listeria monocytogenes can maintain its niche and does not cause host cell death while invasion, growth, replication and dissemination, making it a successful pathogen that can avoid being detected and cleared by the host immune system extracellularly. Therefore, it is a wonderful model microorganism to study host-pathogen interaction.
I have spent my past seven years on mechanism study of cell death in mammalian cells, and now I focus on understanding host-pathogen interaction, especially on how Listeria monocytogenes avoids surveillance and killing by host cells and how it protects its niche without causing host cell death.
Impact in China
Listeriosis ranks third in total number of deaths among foodborne bacterial pathogens, with fatality rates exceeding even Salmonella spp. in the US. Listeria contamination is also a big problem in China because this bacterium can grow at temperatures as low as 0 ℃ permitting its multiplication at typical refrigeration temperatures. With the training at UC Berkeley, I hope to provide new insights into our understanding of the strategies Listeria uses to protect its niche and to combat host detection and killing, and also provide theoretical basis for therapeutics against Listeria infection.
Publications
1. Zhang Y#, Chen X, Gueydan C, Han J*. Plasma membrane changes during programmed cell deaths. Cell Res. 2017 Oct 27. doi: 10.1038/cr.2017.133.
2. Zhang Y#, Su SS#, Zhao S, Yang Z, Zhong CQ, Chen X, Cai Q, Yang ZH, Huang D, Wu R, Han J*. RIP1 autophosphorylation is promoted by mitochondrial ROS and is essential for RIP3 recruitment into necrosome. Nat Commun. 2017 Feb 8; 8: 14329. doi: 10.1038/ncomms14329
3. Zhang Y#, Han J*. Electrophysiologist shows a cation channel function of MLKL. Cell Res. 2016 Jun; 26(6): 643-4.
4. Yang Z#, Wang Y, Zhang Y, He X, Zhong CQ, Ni H, Chen X, Liang Y, Wu J, Zhao S, Zhou D, Han J*. RIP3 targets pyruvate dehydrogenase complex to increase aerobic respiration in TNF-induced necroptosis. Nat Cell Biol. 2018 Feb;20(2):186-197. doi: 10.1038/s41556-017-0022-y.
5. Ren J#, Jia X, Zhao Y, Shi W, Lu J, Zhang Y, Wu J, Liang B, Wu R, Fu G, Han J*. The RIP3-RIP1-NF-κB signaling axis is dispensable for necroptotic cells to elicit cross-priming of CD8+ T cells. Cell Mol Immunol. 2017 Jul;14(7):639-642.
6. Huang D#, Zheng X#, Wang ZA#, Chen X, He WT, Zhang Y, Xu JG, Zhao H, Shi W, Wang X, Zhu Y, Han J*. MLKL channel in necroptosis is octamer formed by tetramers in a dyadic process. Mol Cell Biol. 2017 Feb 15; 37(5)
7. Li, Y. #, Zhong, C.Q. #, Xu, X., Cai, S., Wu, X., Zhang, Y., Chen, J., Shi, J., Lin, S., and Han, J*. Group-DIA: analyzing multiple data-independent acquisition mass spectrometry data files. Nat Methods. Nat Methods. 2015 Oct 5. doi: 10.1038/nmeth.3593.
8. Wu XN#, Yang ZH#, Wang XK, Zhang Y, Wan H, Song Y, Chen X, Shao J, Han J*. Distinct roles of RIP1-RIP3 hetero- and RIP3-RIP3 homo-interaction in mediating necroptosis. Cell Death Differ. 2014 Jun 6. doi: 10.1038/cdd.2014.77.
9. Wu T#, Li Y, Huang D, Han F, Zhang YY, Zhang DW, Han J*. Regulator of G-Protein Signaling 19 (RGS19) and Its Partner Gα-Inhibiting Activity Polypeptide 3 (GNAI3) Are Required for zVAD-Induced Autophagy and Cell Death in L929 Cells. PLoS One. 2014; 9(4): e94634.
10. Wu J#, Huang Z#, Ren J#, Zhang Z, He P, Li Y, Ma J, Chen W, Zhang Y, Zhou X, Yang Z, Wu SQ, Chen L, Han J*. Mlkl knockout mice demonstrate the indispensable role of Mlkl in necroptosis. Cell Res. 2013; 23(8): 994-1006.
11. Chen W#, Zhou Z#, Li L#, Zhong CQ, Zheng X, Wu X, Zhang Y, Ma H, Huang D, Li W, Xia Z, Han J*. Diverse Sequence Determinants Control Human and Mouse Receptor Interacting Protein 3 (RIP3) and Mixed Lineage Kinase Domain-Like (MLKL) Interaction in Necroptotic Signaling. J Biol Chem. 2013; 288(23): 16247-61.
12. Wu X#, Tian L#, Li J, Zhang Y, Han V, Li Y, Xu X, Li H, Chen X, Chen J, Jin W, Xie Y, Han J*, Zhong CQ*. Investigation of RIP3-dependent protein phosphorylation by quantitative phosphoproteomics. Mol Cell Proteomics. 2012; 11(12): 1640-51.