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About

I run a laboratory at the Walter and Eliza Hall Institute (WEHI) in Melbourne, Australia, and am the Science Director of Mermaid Bio, a new biotech startup with its headquarters in Munich.

Our research focuses on the receptors and molecular signalling networks that cause cell death and inflammation. A particular interest is understanding how the potent pro-inflammatory protein, interleukin-1 (IL-1), is activated and promotes pathology in inflammatory diseases. Understanding how IL-1 activity is controlled will allow the targeted design of next-generation anti-inflammatory therapeutics.

Our recent research revealed molecular links between apoptotic and necroptotic cell death and inflammatory cytokine production, including inflammasome activity. We are continuing to decipher exactly how cell death and inflammation are inextricably linked at the molecular level, with our studies implicating specific cell death modalities and inflammasome signalling in diseases such as gout, cytokine shock syndromes, cancer and infections such as SARS-Cov-2 and Legionnaires’ disease.

Our ultimate goal is to use genetics, biochemistry, and disease modelling to understand how cell death and inflammation are controlled, and how they influence each other, as a basis for new treatments. To progress this goal and develop therapies against disease-causing proteins WEHI has teamed up with Mermaid Bio. Together, we are developing new “intrabody” therapies – where lipid nanoparticles, such as those used in the COVID-19 vaccines, are being harnessed to delivery mRNAs encoding for therapeutic nanobodies, a type of antibody that can be generated to target any intracellular protein of interest, and which has several advantages when compared to small molecule compounds.

Publications

Selected publications from A/Prof James Vince

Lee C, Park M, Wijesinghe WCB, Na S, Lee CG, Hwang E, Yoon G, Lee JK, Roh D-H, Kwon YH, Yang J, Hughes SA, Vince JE, Seo JK, Min D, Kwon T-H. Oxidative photocatalysis on membranes triggers non-canonical pyroptosis. Nature Communications. 2024;15(1):10.1038/s41467-024-47634-5

Tran HT, Kratina T, Coutansais A, Michalek D, Hogan BM, Lawlor KE, Vince JE, Silke J, Lalaoui N. RIPK3 cleavage is dispensable for necroptosis inhibition but restricts NLRP3 inflammasome activation. Cell Death & Differentiation. 2024;31(5):10.1038/s41418-024-01281-x

Lawlor KE, Murphy JM, Vince JE. Gasdermin and MLKL necrotic cell death effectors: Signaling and diseases. Immunity. 2024;57(3):10.1016/j.immuni.2024.02.011

Vince JE. IFNγ: Priming for death. Journal of Cell Biology. 2024;223(3):10.1083/jcb.202401127

Guzman LGM, Hyland CD, Bidgood GM, Leong E, Shen Z, Goh W, Rautela J, Vince JE, Nicholson SE, Huntington ND. CD45 limits early Natural Killer cell development. Immunology and Cell Biology. 2024;102(1):10.1111/imcb.12701

Simpson DS, Anderton H, Yousef J, Vaibhav V, Cobbold SA, Bandala-Sanchez E, Kueh AJ, Dagley LF, Herold MJ, Silke J, Vince JE, Feltham R. Mind bomb 2 limits inflammatory dermatitis in Sharpin mutant mice independently of cell death. PNAS Nexus. 2023;3(1):10.1093/pnasnexus/pgad438

Speir M, Tye H, Gottschalk TA, Simpson DS, Djajawi TM, Deo P, Ambrose RL, Conos SA, Emery J, Abraham G, Pascoe A, Hughes SA, Weir A, Hawkins ED, Kong I, Herold MJ, Pearson JS, Lalaoui N, Naderer T, Vince JE, Lawlor KE. A1 is induced by pathogen ligands to limit myeloid cell death and NLRP3 inflammasome activation. EMBO Reports. 2023;24(11):10.15252/embr.202356865

Pang J, Vince JE. The role of caspase-8 in inflammatory signalling and pyroptotic cell death. Seminars in Immunology. 2023;70:10.1016/j.smim.2023.101832

Jeon Y, Chow SH, Stuart I, Weir A, Yeung AT, Hale C, Sridhar S, Dougan G, Vince JE, Naderer T. FBXO11 governs macrophage cell death and inflammation in response to bacterial toxins. Life Science Alliance. 2023;6(6):10.26508/lsa.202201735

Hughes SA, Lin M, Weir A, Huang B, Xiong L, Chua NK, Pang J, Santavanond JP, Tixeira R, Doerflinger M, Deng Y, Yu C, Silke N, Conos SA, Frank D, Simpson DS, Murphy JM, Lawlor KE, Pearson JS, Silke J, Pellegrini M, Herold MJ, Poon IKH, Masters SL, Li M, Tang Q, Zhang Y, Rashidi M, Geng L, Vince JE. Caspase‐8‐driven apoptotic and pyroptotic crosstalk causes cell death and IL‐1β release in X‐linked inhibitor of apoptosis (XIAP) deficiency. The EMBO Journal. 2023;42(5):10.15252/embj.2021110468

Lab research projects

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