Cell Death and Inflammatory Signalling

Overview

The Cell Death and Inflammatory Signalling group aims to identify new molecules that regulate cell death and inflammatory signalling. We also seek to establish whether cell death signalling can be inhibited therapeutically to treat inflammatory disease or triggered to promote antimicrobial responses.

Dr Lawlor and her team investigate the cross-talk between programmed cell death and inflammatory signalling pathways in disease. In particular, the laboratory studies how cell death induces activation of the NLRP3 inflammasome. Inflammasomes activate pro-inflammatory proteins Interleukin-1β (IL-1β) and IL-18 and induce a lytic form of cell death, called pyroptosis. This activity is critical for clearance of microbial organisms by the immune system. However, excess IL-1β activity can exacerbate rare hereditary autoinflammatory syndromes and common diseases, such as rheumatoid arthritis, type 2 diabetes and cancer.

The Lawlor group utilise a range of cellular and molecular biology methods and preclinical disease models.

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Diseases we research

Research Group Head | Associate Professor Kate Lawlor

Inflammation is at the heart of numerous diseases and new research has found that the timing of cell death is crucial to this process. My research uses host cell factor targeting to combat difficult-to-treat infections and the growing threat of antibiotic-resistance.

Associate Professor Kate Lawlor from the Cell Death and Inflammatory Signalling Research Group at Hudson Institute

Meet the team

News from the lab

22 November 2023

Double trouble for tumour cells

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Student opportunities

Publication highlights

Vince JE*, De Nardo D, Gao W, Vince AJ, Hall C, McArthur K, Simpson D, Vijayaraj S, Lindqvist LM, Bouillet P, Rizzacasa M, Man SM, Silke J, Masters SL, Lessene G, Huang DCS, Gray DHD, Kile BT, Shao F, Lawlor KE* (2018) The Mitochondrial Apoptotic Effectors BAX/BAK Activate Caspase-3 and -7 to Trigger NLRP3 Inflammasome and Caspase-8 Driven IL-1b Activation. Cell Reports 25(9):2339-2353 * co-corresponding authors
Lawlor KE*‡, Feltham RL*, 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†‡ (2017) XIAP Loss Triggers RIPK3 and Caspase-8-Driven IL-1b activation and Cell Death as a Consequence of TLR-MyD88-induced cIAP1-TRAF2 degradation. Cell Reports 20(3):668-682. *,† equal contribution; ‡ co-corresponding authors
Conos SA, Chen KW, De Nardo D, Whitehead L, Hara H, Vaux DL, Nùñez G, Masters SL, Murphy JM, Schroder K, Lawlor KE*, Lindqvist LM*, Vince JE* *co-senior/corresponding authors (2017) Active MLKL triggers the NLRP3 inflammasome in a cell intrinsic manner. Proceedings of the National Academy of Sciences USA 114:E961-E969.
Lawlor KE*, Khan N, Mildenhall A, Gerlic M, Croker BA, D’Cruz AA, Hall C, Spall S, Anderton H, Masters SL, Rashidi M, Wicks IP, Alexander WS, Mitsuuchi Y, Benetatos CA, Condon SM, Wong WW, Silke J†, Vaux DL† Vince JE*† (2015) RIPK3 promotes cell death and NLRP3 inflammasome activation in the absence of MLKL. Nature Communications 6:6282. *co-corresponding authors, † these authors jointly supervised this work.
Allam R*, Lawlor KE*, Yu EC, Mildenhall AL, Moujalled DM, Lewis RS, Ke F, Mason KD, White MJ, Stacey KJ, Strasser A, Alexander W, Kile BT, Vaux DL, Vince JE *Joint first authors (2014) Mitochondrial apoptosis is dispensable for NLRP3 inflammasome activation but non-apoptotic caspase-8 is required for inflammasome priming. EMBO Reports 15:982-990.
Lawlor KE, van Nieuwenhuijze A, Parker KL, Drake SF, Campbell IK, Smith SD, Vince JE, Strasser A, Wicks IP (2013) Bcl-2 overexpression ameliorates immune complex-mediated arthritis by altering FcγRIIb expression and monocyte homeostasis. Journal of Leukocyte Biology 93: 585-597.
Lawlor KE, Smith SD, van Nieuwenhuijze A, Huang DC, Wicks IP (2011) Evaluation of Bcl-2 antagonist ABT-737 in collagen-induced arthritis. Journal of Leukocyte Biology 90:819-829.
Speir M, Lawlor KE (2020) RIP-roaring inflammation: RIPK1 and RIPK3 driven NLRP3 inflammasome activation and autoinflammatory disease. Seminars in Cell and Developmental Biology S1084-9521(19)30233-2.
Yabal M, Calleja DJ, Simpson DS, Lawlor KE (2019) Stressing out the mitochondria: Mechanistic insights NLRP3 inflammasome activation. Journal of Leukocyte Biology 105(2):377-399.
Giogha C, Lawlor KE (2019) Sugar Fix Keeps RIPK3 at Bay. Immunity 50(3):539-541.
Lawlor, KE, Conos, SA, Vince, JE (2018) Pyroptosis. In Apoptosis and Beyond: The Many Ways Cells Die Radosevich J ed. Hoboken, NJ: John Wiley & Sons. pp. 317-342. https://doi.org/10.1002/9781119432463.ch15.
Feltham R, Vince JE, Lawlor KE (2017) Caspase-8: not so silently deadly. Clinical and Translational Immunology 6(1):e124.
Lawlor KE, Vince JE (2014) Ambiguities in NLRP3 inflammasome regulation: is there a role for mitochondria? Biochimica et Biphysica Acta 1840(4):1433-1440.
Khan N*, Lawlor KE*, Murphy JM, Vince JE (2014) More to Life than death: molecular determinants of necroptotic and non-necroptotic RIP3 kinase signaling Current Opinion in Immunology 26:76-89 *co-first authors

Our research group is keen to discuss funding opportunities

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Cell Death and Inflammatory Signalling

Overview

Diseases we research

Research Group Head | Associate Professor Kate Lawlor

Meet the team

News from the lab

How does cell death trigger inflammation?

T cells open the door to potential immune therapies

Finding the triggers of inflammation

Strengthening international collaborations with the University of Toronto

NHMRC Ideas Grant success

Australian Research Council (ARC) Future Fellowship

Hudson Institute welcomes Young Women in Science

Double trouble for tumour cells

Student opportunities

Publication highlights

Our research group is keen to discuss funding opportunities