Innate Immune and Autoinflammatory Disease

The human immune system recognises and responds to infections but can overreact due to factors like age, environment, or genetic alterations, leading to autoinflammatory diseases. We focus on diagnosing and treating these conditions.

Overview

Autoinflammatory diseases can present anytime from very early in life with severe systemic symptoms such as fevers, swelling, redness, and pain. Diagnosis is typically delayed, requiring extensive investigations to rule out other conditions.

Professor Seth Masters and his team in the Innate Immune and Autoinflammatory Disease Research group manages the Australian Autoinflammatory Disease Registry, which aims to increase the rates of genetic diagnosis and gain insights into novel mechanisms for therapeutic development.

The group’s research aims to identify new forms of autoinflammatory diseases, exploring ways to target innate immune pathways to address inflammation associated with chronic and neurodegenerative conditions.

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Diseases we research

Areas of focus

Identify new innate immune pathways causing autoinflammatory disease.
Validate the pathogenicity of variants in inflammasome sensors.
Determine how G-CSF and type I IFNs contribute to chronic inflammatory or neuroinflammatory pathology.

Research Group Head | Professor Seth Masters

Auto-inflammatory diseases stem from an overactive innate immune system. My research aims to identify the underlying causes of auto-inflammatory diseases, which is crucial for determining the most effective treatment strategies.

Professor Seth Masters, Centre Head of the Centre for Innate Immunity and Infectious Diseases

Meet the team

News from the lab

15 April 2024

New arrivals boost Hudson’s inflammation research leadership

14 December 2023

Hudson Institute welcomes inflammation specialist as new Centre Head

Student opportunities

Collaborators

Publication highlights

Davidson S, Yu CH, Steiner A, Ebstein F, Baker PJ, Jarur-Chamy V, Hrovat Schaale K, Laohamonthonkul P, Kong K, Calleja DJ, Harapas CR, Balka KR, Mitchell J, Jackson JT, Geoghegan ND, Moghaddas F, Rogers KL, Mayer-Barber KD, De Jesus AA, De Nardo D, Kile BT, Sadler AJ, Poli MC, Krüger E, Goldbach Mansky R, Masters SL. (2022) Protein kinase R is an innate immune sensor of proteotoxic stress via accumulation of cytoplasmic IL-24. Sci Immunol. 11;7(68) PMID: 35148201. Full text
Steiner A, Reygaerts T, Pontillo A, Ceccherini I, Moecking J, Moghaddas F, Davidson S, Caroli F, Grossi A, Castro FFM, Kalil J, Gohr FN, Schmidt FI, Bartok E, Zillinger T, Hartmann G, Geyer M, Gattorno M, Mendonça LO, Masters SL. (2022) Recessive NLRC4-Autoinflammatory Disease Reveals an Ulcerative Colitis Locus. J Clin Immunol. Feb;42(2):325-335. PMID: 34783940
Moecking J, Laohamonthonkul P, Chalker K, White MJ, Harapas CR, Yu CH, Davidson S, Hrovat-Schaale K, Hu D, Eng C, Huntsman S, Calleja DJ, Horvat JC, Hansbro PM, O’Donoghue RJJ, Ting JP, Burchard EG, Geyer M, Gerlic M, Masters SL. (2021) NLRP1 variant M1184V decreases inflammasome activation in the context of DPP9 inhibition and asthma severity. J Allergy Clin Immunol. Jun;147(6):2134-2145. PMID: 33378691
Yu CH, Davidson S, Harapas CR, Hilton JB, Mlodzianoski MJ, Laohamonthonkul P, Louis C, Low RRJ, Moecking J, De Nardo D, Balka KR, Calleja DJ, Moghaddas F, Ni E, McLean CA, Samson AL, Tyebji S, Tonkin CJ, Bye CR, Turner BJ, Pepin G, Gantier MP, Rogers KL, McArthur K, Crouch PJ, Masters SL. (2020) TDP-43 Triggers Mitochondrial DNA Release via mPTP to Activate cGAS/STING in ALS. Cell. Oct 29;183(3):636-649. PMID: 33031745
Tye H, Yu CH, Simms LA, de Zoete MR, Kim ML, Zakrzewski M, Penington JS, Harapas CR, Souza-Fonseca-Guimaraes F, Wockner LF, Preaudet A, Mielke LA, Wilcox SA, Ogura Y, Corr SC, Kanojia K, Kouremenos KA, De Souza DP, McConville MJ, Flavell RA, Gerlic M, Kile BT, Papenfuss AT, Putoczki TL, Radford-Smith GL, Masters SL. (2018) NLRP1 restricts butyrate producing commensals to exacerbate inflammatory bowel disease. Nat Commun. Sep 13;9(1):3728. PMID: 30214011
Moghaddas F, Zeng P, Zhang Y, Schützle H, Brenner S, Hofmann SR, Berner R, Zhao Y, Lu B, Chen X, Zhang L, Cheng S, Winkler S, Lehmberg K, Canna SW, Czabotar PE, Wicks IP, De Nardo D, Hedrich CM, Zeng H, Masters SL. (2018) Autoinflammatory mutation in NLRC4 reveals a leucine-rich repeat (LRR)-LRR oligomerization interface. J Allergy Clin Immunol. Dec;142(6):1956-1967 PMID: 29778503
Murphy AJ, Kraakman MJ, Kammoun HL, Dragoljevic D, Lee MK, Lawlor KE, Wentworth JM, Vasanthakumar A, Gerlic M, Whitehead LW, DiRago L, Cengia L, Lane RM, Metcalf D, Vince JE, Harrison LC, Kallies A, Kile BT, Croker BA, Febbraio MA, Masters SL. (2016) IL-18 Production from the NLRP1 Inflammasome Prevents Obesity and Metabolic Syndrome. Cell Metab. Jan 12;23(1):155-64. PMID: 26603191
Masters SL, Lagou V, Jeru I, Baker PJ, Van Eyck L, Parry DA, Lawless D, De Nardo D, Garcia-Perez JE, Dagley LF, Holley CL, Dooley J, Moghaddas F, Pasciuto E, Jeandel PY, Sciot R, Lyras D, Webb AI, Nicholson SE, De Somer L, van Nieuwenhove E, Ruuth-Praz J, Copin B, Cochet E, Medlej-Hashim M, Megarbane A, Schroder K, Savic S, Goris A, Amselem S, Wouters C, Liston A. (2016) Familial autoinflammation with neutrophilic dermatosis reveals a regulatory mechanism of pyrin activation. Sci Transl Med. Mar 30;8(332):332ra45. PMID: 27030597
Kim ML, Chae JJ, Park YH, De Nardo D, Stirzaker RA, Ko HJ, Tye H, Cengia L, DiRago L, Metcalf D, Roberts AW, Kastner DL, Lew AM, Lyras D, Kile BT, Croker BA, Masters SL. (2015) Aberrant actin depolymerization triggers the pyrin inflammasome and autoinflammatory disease that is dependent on IL-18, not IL-1beta. J Exp Med. Jun 1;212(6):927-38. PMID: 26008898
Masters SL, Gerlic M, Metcalf D, Preston S, Pellegrini M, O’Donnell JA, McArthur K, Baldwin TM, Chevrier S, Nowell CJ, Cengia LH, Henley KJ, Collinge JE, Kastner DL, Feigenbaum L, Hilton DJ, Alexander WS, Kile BT, Croker BA. (2012) NLRP1 inflammasome activation induces pyroptosis of hematopoietic progenitor cells. Immunity. Dec 14;37(6):1009-23. PMID: 23219391

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