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 modalitites 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 nanaparticles, 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.


Selected publications from A/Prof James Vince

Caspase-8-driven apoptotic and pyroptotic crosstalk causes cell death and IL-1β release in X-linked inhibitor of apoptosis (XIAP) deficiency.
Hughes SA, Lin M, Weir A, Huang B, Xiong L, Chua NK, Pang J, Santavanond JP, Tixeira R, Doerflinger M, Deng Y, Yu CH, 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. EMBO J. 2023 Jan 17:e110468. doi:

Interferon-γ primes macrophages for pathogen ligand-induced killing via a caspase-8 and mitochondrial cell death pathway.
Simpson DS, Pang J, Weir A, Kong IY, Fritsch M, Rashidi M, Cooney JP, Davidson KC, Speir M, Djajawi TM, Hughes S, Mackiewicz L, Dayton M, Anderton H, Doerflinger M, Deng Y, Huang AS, Conos SA, Tye H, Chow SH, Rahman A, Norton RS, Naderer T, Nicholson SE, Burgio G, Man SM, Groom JR, Herold MJ, Hawkins ED, Lawlor KE, Strasser A, Silke J, Pellegrini M, Kashkar H, Feltham R, Vince JE. Immunity. 2022 Mar 8;55(3):423-441.e9. doi: 10.1016/j.immuni.2022.01.003. Epub 2022 Feb 8. PMID: 35139355

Ubiquitylation of RIPK3 beyond-the-RHIM can limit RIPK3 activity and cell death.
Frank D, Garnish S, Sandow JJ, Weir A, Liu L, Clayer E, Meza L, Rashidi M, Cobbold SA, Scutts SR, Doerflinger M, Anderton H, Lawlor KE, Lalaoui N, Keuh AJ, Eng VV, Ambrose, RL, Herold MJ, Samson AL, Feltham RF, Murphy JM, Ebert G, Pearson JS, Vince JE. iScience. 2022. Jun 17;25(7):104632. doi: 10.1016/j.isci.2022.104632. eCollection 2022 Jul 15.

The ubiquitylation of IL-1β limits its cleavage by caspase-1 and targets it for proteasomal degradation.
Vijayaraj SL, Feltham R, Rashidi M, Frank D, Liu Z, Simpson DS, Ebert G, Vince A, Herold MJ, Kueh A, Pearson JS, Dagley LF, Murphy JM, Webb AI, Lawlor KE, Vince JE. Nat Communications. 2021 May 11;12(1):2713. doi: 10.1038/s41467-021-22979-3. PMID: 33976225

The Pyroptotic Cell Death Effector Gasdermin D Is Activated by Gout-Associated Uric Acid Crystals but Is Dispensable for Cell Death and IL-1β Release.
Rashidi M, Simpson DS, Hempel A, Frank D, Petrie E, Vince A, Feltham R, Murphy J, Chatfield SM, Salvesen GS, Murphy JM, Wicks IP, Vince JE. J Immunol. 2019 Aug 1;203(3):736-748. doi: 10.4049/jimmunol.1900228. Epub 2019 Jun 17. PMID: 31209100

The Mitochondrial Apoptotic Effectors BAX/BAK Activate Caspase-3 and -7 to Trigger NLRP3 Inflammasome and Caspase-8 Driven IL-1β Activation.
Vince JE*, De Nardo D, Gao W, Vince AJ, Hall C, McArthur K, Simpson D, Vijayaraj S, Lindqvist LM, Bouillet P, Rizzacasa MA, Man SM, Silke J, Masters SL, Lessene G, Huang DCS, Gray DHD, Kile BT, Shao F, Lawlor K*. Cell Reports. 2018 Nov 27;25(9):2339-2353.e4. doi: 10.1016/j.celrep.2018.10.103. PMID: 30485804

XIAP Loss Triggers RIPK3- and Caspase-8-Driven IL-1β Activation and Cell Death as a Consequence of TLR-MyD88-Induced cIAP1-TRAF2 Degradation.
Lawlor KE, Feltham R, Yabal M, Conos SA, Chen KW, Ziehe S, Graß C, Zhan Y, Nguyen TA, Hall C, Vince AJ, Chatfield SM, D’Silva DB, Pang KC, Schroder K, Silke J, Vaux DL, Jost PJ, Vince JE. Cell Reports. 2017 Jul 18;20(3):668-682. doi: 10.1016/j.celrep.2017.06.073. PMID: 28723569

Active MLKL triggers the NLRP3 inflammasome in a cell-intrinsic manner.
Conos SA, Chem KW, De Nardo D, Hara H, Whitehead L, Núñez G, Masters SL, Murphy JM, Schroder K, Vaux DL, Lawlor KE, Lindqvist LM, Vince JE. Proc Natl Acad Sci U S A. 2017 Feb 7;114(6):E961-E969. PMID: 28096356

Eliminating Legionella by inhibiting BCL-XL to induce macrophage apoptosis.
Speir M, Lawlor KE, Glaser SP, Abraham G, Chow S, Vogrin A, Schulze KE, Schuelein R, O’Reilly LA, Mason K, Hartland EL, Lithgow T, Strasser A, Lessene G, Huang DCS, Vince JE*, Naderer T*. Nature Microbiology. 2016. 1:15034.

RIPK3 promotes cell death and NLRP3 inflammasome activation in the absence of MLKL.
Lawlor KE, Khan N, Mildenhall A, Gerlic M, Croker BA, D’Cruz AA, Hall C, Kaur Spall S, Anderton H, Masters SL, Rashidi M, Wicks IP, Alezander WS, Mitsuuchi Y, Benetatos CA, Condon SM, Wong WW, Silke J, Vaux DL, Vince JE. Nat Communications. 2015 Feb 18;6:6282. PMID: 25693118

Mitochondrial apoptosis is dispensable for NLRP3 inflammasome activation but non-apoptotic caspase-8 is required for inflammasome priming.
Allam R, Lawlor KE, Yu EC, Mildenhall AL, Moujalled DM, Lewis RS, Ke F, Mason KD, White MJ, Stacey KJ, Strasser A, O’Reilly LA, Alexander W, Kile BT, Vaux DL, Vince JE. EMBO Reports. 2014 Jul 2. PMID: 24990442.

Inhibitor of apoptosis proteins limit RIP3 kinase-dependent interleukin-1 activation.
Vince JE, Wong WW, Gentle I, Lawlor KE, Allam R, O’Reilly L, Mason K, Gross O, Ma S, Guarda G, Anderton H, Castillo R, Hacker G, Silke J, Tschopp J. Immunity. 2012 Feb 24;36(2):215-27. PMID: 22365665.

IAP antagonists target cIAP1 to induce TNFalpha-dependent apoptosis.
Vince JE, Wong WW, Khan N, Feltham R, Chau D, Ahmed AU, Benetatos CA, Chunduru SK, Condon SM, McKinlay M, Brink R, Leverkus M, Tergaonkar V, Schneider P, Callus BA, Koentgen F, Vaux DL, Silke J. Cell. 2007 Nov 16;131(4):682-93. PMID: 18022363

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