Dr Seth Masters
Our lab studies inflammation generated by the innate immune system. This can happen in many different contexts, for example during a bacterial or viral infection; when cells die during an organ or tissue transplant; or when genetic mutations activate innate immune pathways. The innate immune response is also fundamentally involved in the pathogenesis of many chronic inflammatory diseases such as rheumatoid arthritis, Crohns disease and even type 2 diabetes.
Previously we have made discoveries relevant to all of these areas, and we maintain close links to industry and the clinic to make sure our discoveries can continue to have a direct effect on human health in the future.
A particular focus for the lab is a family of innate immune receptors known as Nod-Like Receptors (NLRs). Many of these have the capacity to form cytoplasmic protein complexes (inflammasomes), which are biological structures that process the pro-inflammatory cytokines IL-1β and IL-18 into their mature forms. Our research has identified substances that activate the inflammasome, and mechanisms by which this inflammation causes disease.
This is a particularly exciting time to be working on inflammation because so many new drugs are coming to the clinic, and we have the diverse research tools to determine where and why these can provide benefit.
- Haneklaus M, Gerlic M, Kurowska-Stolarska M, Rainey AA, Pich D, McInnes IB, Hammerschmidt W, O'Neill LA, Masters SL. Cutting edge: miR-223 and EBV miR-BART15 regulate the NLRP3 inflammasome and IL-1β production. J Immunol. 2012 Oct 15;189(8):3795-9. PMID: 22984081
- 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. NLRP1 inflammasome activation induces pyroptosis of hematopoietic progenitor cells. Immunity. 2012 Dec 14;37(6):1009-23. PMID: 23219391
- Masters SL. Specific inflammasomes in complex diseases. Clin Immunol. 2012 Dec 21. PMID: 23294928
- Masters, SL, Latz, E, and O'Neill, LA, The inflammasome in atherosclerosis and type 2 diabetes. Sci Transl Med, 2011. 3: 81ps17. PMID: 21543720
- Masters, SL and O'Neill, LA, Disease-associated amyloid and misfolded protein aggregates activate the inflammasome. Trends Mol Med, 2011. 17: 276-82. PMID: 21376667
- Masters, SL, Dunne, A, Subramanian, SL, Hull, RL, Tannahill, GM, Sharp, FA, Becker, C, Franchi, L, Yoshihara, E, Chen, Z, Mullooly, N, Mielke, LA, Harris, J, Coll, RC, Mills, KH, Mok, KH, Newsholme, P, Nunez, G, Yodoi, J, Kahn, SE, Lavelle, EC, and O'Neill, LA, Activation of the NLRP3 inflammasome by islet amyloid polypeptide provides a mechanism for enhanced IL-1beta in type 2 diabetes. Nat Immunol, 2010. 11: 897-904. PMID: 20835230
- Masters, SL, Mielke, LA, Cornish, AL, Sutton, CE, O'Donnell, J, Cengia, LH, Roberts, AW, Wicks, IP, Mills, KH, and Croker, BA, Regulation of interleukin-1beta by interferon-gamma is species specific, limited by suppressor of cytokine signalling 1 and influences interleukin-17 production. EMBO Rep, 2010. 11: 640-6. PMID: 20596075
- Aksentijevich, I, Masters, SL, Ferguson, PJ, Dancey, P, Frenkel, J, van Royen-Kerkhoff, A, Laxer, R, Tedgard, U, Cowen, EW, Pham, TH, Booty, M, Estes, JD, Sandler, NG, Plass, N, Stone, DL, Turner, ML, Hill, S, Butman, JA, Schneider, R, Babyn, P, El-Shanti, HI, Pope, E, Barron, K, Bing, X, Laurence, A, Lee, CC, Chapelle, D, Clarke, GI, Ohson, K, Nicholson, M, Gadina, M, Yang, B, Korman, BD, Gregersen, PK, van Hagen, PM, Hak, AE, Huizing, M, Rahman, P, Douek, DC, Remmers, EF, Kastner, DL, and Goldbach-Mansky, R, An autoinflammatory disease with deficiency of the interleukin-1-receptor antagonist. N Engl J Med, 2009. 360: 2426-37. PMID: 19494218
- Masters, SL, Simon, A, Aksentijevich, I, and Kastner, DL, Horror autoinflammaticus: the molecular pathophysiology of autoinflammatory disease (*). Annu Rev Immunol, 2009. 27: 621-68. PMID: 19302049
- Masters, SL, Yao, S, Willson, TA, Zhang, JG, Palmer, KR, Smith, BJ, Babon, JJ, Nicola, NA, Norton, RS, and Nicholson, SE, The SPRY domain of SSB-2 adopts a novel fold that presents conserved Par-4-binding residues. Nat Struct Mol Biol, 2006. 13: 77-84. PMID: 16369487
Current Laboratory Members
Laboratory Head: Seth Masters, Dip Arts (Philos), BSc (Hons), PhD Melb
Senior Postdoctoral Fellow: Motti Gerlic, BSc, PhD Israel
Postdoctoral Fellow: Man Lyang Kim, BSc, MSc South Korea, PhD Basel
Postgraduate Student: Joanne O'Donnell, BSc(Hons) Melb
Undergraduate Student: Alison Mildenhall, BSc Sydney