Assistant Professor Chen Kaiwen

Research Interest

Myeloid cells such as macrophages and neutrophils express a repertoire of pattern recognition receptors to protect against microbial invasion, however, dysregulation in these pathways are increasingly recognised to drive autoinflammatory diseases.
Our laboratory studies the mechanisms by which inflammation is initiated and terminated by the innate immune system. A major interest of the lab is to understand how various programmed cell death pathways including apoptosis, pyroptosis and necroptosis are initiated during microbial infection and consequently how these death pathways promote host immunity in vivo. We also use a range of microbial mutants to define the corresponding microbial subversion mechanisms. The knowledge gained from these studies will improve our understanding of host-pathogen interactions and may unravel novel antimicrobial therapeutics and regulations of inflammation.

Recent Publications

1. Yeap HW and Chen KW. RIPK1 and RIPK3 in antibacterial defence. Biochem Soc Trans, 2022, 50 (6): 1583-1594.
2. Yow SJ, Yeap HW, Chen KW. Inflammasome and gasdermin signaling in neutrophils. Mol Microbiol, 2022, 5;117(5):961-972.
3. Chen KW#, Demarco B, Ramos S, Heilig R, Goris M, Grayczyk JP, Assenmacher CA, Radaelli E, Joannas LD, Henao-Mejia J, Tacchini-Cottier F, Brodsky IE, Broz P#. RIPK1 activates distinct gasdermins in macrophages and neutrophils upon pathogen blockade of innate immune signalling. PNAS, 2021, 118(28). #Corresponding author
4. Demarco B, Grayczyk JP, Bjanes E, Le Roy D, Tonnus W, Assenmacher C-A, Radaelli E, Fettrelet T, Mack V, Linkermann A, Roger T, Brodsky IE, Chen KW#, Broz P#Caspase-8-dependent gasdermin D cleavage promotes anti-microbial defence but confers susceptibility to TNF-induced lethality. Sci Adv, in press. #Corresponding authors
5. Chen KW#, Demarco B, Broz P#. Pannexin-1 promotes NLRP3 activation during apoptosis but is dispensable for canonical or non‐canonical inflammasome activation. Euro J Immunol, 2020, 50: 170–177. #Corresponding authors
6. Chen KW*, Demarco B*, Heilig R, Shkarina K, Boettcher A, Farady CJ, Pelczar P, Broz P. Extrinsic and intrinsic apoptosis activate Pannexin-1 to drive NLRP3 inflammasome assembly. EMBO J, 2019, e101638. *equal contribution.
7. Chen KW*, Monteleone M*, Boucher D*, Sollberger G, Ramnath D, Condon ND, von Pein JP, Broz P, Sweet MJ, Schroder K. Noncanonical inflammasome signaling elicits gasdermin D–dependent neutrophil extracellular traps. Sci Immunol, 2018, 3, eaar6676. *equal contribution.
8. Chen KW, Lawlor KE, von Pein JB, Boucher D, Gerlic M, Croker BA, Bezbradica JS, Vince JE, and Schroder K. Cutting Edge: Blockade of Inhibitor of Apoptosis Proteins Sensitizes Neutrophils to TNF- but Not Lipopolysaccharide-Mediated Cell Death and IL-1beta Secretion. J Immunol, 2018, 200: 3341-3346.
9. Boucher D, Monteleone M*, Coll RC*, Chen KW*, Ross CM, Teo JL, Gomez GA, Holley CL, Bierschenk D, Stacey KJ, Yap AS, Bezbradica JS, and Schroder K. Caspase-1 self-cleavage is an intrinsic mechanism to terminate inflammasome activity. J Exp Med, 2018, 215: 827-840. *equal contribution.
10. Conos SA, Chen KW, De Nardo D, Hara H, Whitehead L, Nunez G, Masters SL, Murphy JM, Schroder K, Vaux DL, Lawlor KE, Lindqvist LM, Vince JE. Active MLKL triggers the NLRP3 inflammasome in a cell-intrinsic manner. PNAS, 2017, 114: E961-E9.