Immunology
We aim to better understand the molecular basis of the immune response and study innate and adaptive immunity. Our group works with human neutrophils, macrophages, dendritic cells, mast cells, complement and T cells, investigating their recruitment, differentiation, signalling and modulation in immunity, and especially the effects of novel drug leads on their functions. We are especially interested in complement proteins, GPCRs, T cell receptors, proteases, HDACs, chemokines and cytokines. Our drugs, after validating targets on human cells and human proteins, are next investigated in rodent models of human diseases and then towards preclinical and clinical studies, either ourselves or with pharma/biotech partners. Understanding how new experimental drugs can stimulate/enhance immune responses or suppress proinflammatory mediators can help in the design and development of effective new therapies to combat a diverse range of important human diseases.
In 2014 we began two new intiatives. We linked up with physicists, structural biologists and immunologists in Melbourne and Sydney to form the ARC Centre of Excellence in Advanced Molecular Imaging to study the molecular basis of immunity. We also helped form a local Centre for Inflammation and Disease Research in Brisbane.
Recent Publications (Immunology)
2023
Das Gupta K, Ramnath D, von Pein JB, Curson JEB, Wang Y, Abrol R, Kakkanat A, Moradi SV, Gunther KS, Murthy AMV, Stocks CJ, Kapetanovic R, Reid RC, Iyer A, Ilka ZC, Nauseef WM, Plan M, Luo L, Stow JL, Schroder K, Karunakaran D, Alexandrov K, Shakespear MR, Schembri MA, Fairlie DP, Sweet MJ.HDAC7 is an immunometabolic switch triaging danger signals for engagement of antimicrobial versus inflammatory responses in macrophages. Proc Natl Acad Sci U S A 2023, 120, e2212813120.
Molecular insights into metabolite antigen recognition by mucosal-associated invariant T cells. Awad W, Ciacchi L, McCluskey J, Fairlie DP, Rossjohn J. Curr Opin Immunol 2023, 83, 102351.
Suppression of MR1 by human cytomegalovirus inhibits MAIT cell activation. Ashley CL, McSharry BP, McWilliam HEG, Stanton RJ, Fielding CA, Mathias RA, Fairlie DP, McCluskey J, Villadangos JA, Rossjohn J, Abendroth A, Slobedman B. Front Immunol 2023, 14, 1107497.
Histone deacetylase 7: a signalling hub controlling development, inflammation, metabolism and disease.Wang Y, Abrol R, Mak JYW, Das Gupta K, Ramnath D, Karunakaran D, Fairlie DP, Sweet MJ. FEBS J 2023, 290, 2805-2832.
2022
CD8 coreceptor engagement of MR1 enhances antigen responsiveness by human MAIT and other MR1-reactive T cells. Souter MNT, Awad W, Li S, Pediongco TJ, Meehan BS, Meehan LJ, Tian Z, Zhao Z, Wang H, Nelson A, Le Nours J, Khandokar Y, Praveena T, Wubben J, Lin J, Sullivan LC, Lovrecz GO, Mak JYW, Liu L, Kostenko L, Kedzierska K, Corbett AJ, Fairlie DP, Brooks AG, Gherardin NA, Uldrich AP, Chen Z, Rossjohn J, Godfrey DI, McCluskey J, Pellicci DG, Eckle SBG. J Exp Med 2022, 219, e20210828.
Quantitative affinity measurement of small molecule ligand binding to major histocompatibility complex class-I-related protein 1 MR1. Wang CJH, Awad W, Liu L, Mak JYW, Veerapen N, Illing PT, Purcell AW, Eckle SBG, McCluskey J, Besra GS, Fairlie DP, Rossjohn J, Le Nours J. J Biol Chem 2022, 298, 102714.
The balance of interleukin-12 and interleukin-23 determines the bias of MAIT1 versus MAIT17 responses during bacterial infection. Wang H, Nelson AG, Wang B, Zhao Z, Lim XY, Shi M, Meehan LJ, Jia X, Kedzierska K, Meehan BS, Eckle SB, Souter MN, Pediongco TJ, Mak JY, Fairlie DP, McCluskey J, Wang Z, Corbett AJ, Chen Z. Immunol Cell Biol 2022, 100, 547-561.
A specialized tyrosine-based endocytosis signal in MR1 controls antigen presentation to MAIT cells. Lim HJ, Wubben JM, Garcia CP, Cruz-Gomez S, Deng J, Mak JYW, Hachani A, Anderson RJ, Painter GF, Goyette J, Amarasinghe SL, Ritchie ME, Roquilly A, Fairlie DP, Gaus K, Rossjohn J, Villadangos JA, McWilliam HEG. J Cell Biol 2022, 221, e202110125.
Inhibition of the master regulator of Listeria monocytogenes virulence enables bacterial clearance from spacious replication vacuoles in infected macrophages. Tran TT, Mathmann CD, Gatica-Andrades M, Rollo RF, Oelker M, Ljungberg JK, Nguyen TTK, Zamoshnikova A, Kummari LK, Wyer OJK, Irvine KM, Melo-Bolívar J, Gross A, Brown D, Mak JYW, Fairlie DP, Hansford KA, Cooper MA, Giri R, Schreiber V, Joseph SR, Simpson F, Barnett TC, Johansson J, Dankers W, Harris J, Wells TJ, Kapetanovic R, Sweet MJ, Latomanski EA, Newton HJ, Guérillot RJR, Hachani A, Stinear TP, Ong SY, Chandran Y, Hartland EL, Kobe B, Stow JL, Sauer-Eriksson AE, Begun J, Kling JC, Blumenthal A. PLoS Pathog 2022, 18, e1010166.
Differential location of NKT and MAIT cells within lymphoid tissue. Johnson DN, Ruan Z, Petley EV, Devi S, Holz LE, Uldrich AP, Mak JYW, Hor JL, Mueller SN, McCluskey J, Fairlie DP, Darcy PK, Beavis PA, Heath WR, Godfrey DI. Sci Rep 2022, 12, 4034.
2021
Chemical modulators of mucosal associated invariant T cells. Mak JYW, Liu L, Fairlie DP. Accounts of Chemical Research 2021, 54, 3462-3475.
MAIT cells regulate NK cell mediated tumor immunity. Petley EV, Koay HF, Henderson MA, Sek K, Todd KL, Keam SK, Lai J, House IG, Li J, Zehoven M, Chen AXY, Oliver AJ, Michie J, Freeman AJ, Giuffrida L, Chan JD, Pizzolla A, Mak JYW, McCulloch TR, Souza-Fonseca-Guimaraes F, Kearney CJ, Millen R, Ramsay RG, Huntington ND, McCluskey J, Oliaro J, Fairlie DP, Neeson PJ, Godfrey DI, Beavis PA, Darcy PK. Nature Commun 2021, 12, 4746.
Taking the Myc out of cancer: Toward therapeutic strategies to directly inhibit c-Myc. S Madden, AD de Araujo, M Gerhardt, DP Fairlie, JM Mason. Molecular Cancer 2021, 20, 3.
De novo macrocyclic peptides for inhibiting, stabilizing, and probing the function of the retromer endosomal trafficking complex. Kai-En Chen, Qian Guo, Timothy A Hill, Yi Cui, Amy K Kendall, Zhe Yang, Ryan J Hall, Michael D Healy, Joanna Sacharz, Suzanne J Norwood, Sachini Fonseka, Boyang Xie, Robert C Reid, Natalya Leneva, Robert G Parton, Rajesh Ghai, David A Stroud, David P Fairlie Science Advances 2021, 7(49), eabg4007.
Mucosal-associated invariant T cells effector function is an intrinsic cell property that can be augmented by the metabolic cofactor α-ketoglutarate. Howson L, Li J, von Borstel A, Barugahare A, Mak J, Fairlie D, McCluskey J, Turner SJ, Davey M, Rossjohn J. J Immunol 2021, 206, 1425-1435.
HDAC7 inhibition by phenacetyl and phenylbenzoyl hydroxamates. Mak JYW, Wu KC, Gupta PK, Barbero S, McLaughlin MG, Lucke AJ, Tng J, Lim J, Loh Z, Sweet MJ, Reid RC, Liu L, Fairlie DP. J Med Chem 2021, 64, 2186-2204.
Targeting class IIa HDACs: insights from phenotypes and inhibitors. Liu L, Dong L, Fairlie DP. Curr Med Chem 2021, 28, 8628–8672.
A nucleotide analog prevents colitis associated cancer via Β-catenin independently of inflammation and autophagy.Sheng YH, Giri R, Davies J, Schreiber V, Alabbas S, Movva R, He Y, Wu A, Hooper J, McWhinney B, Oancea I, Kijanka G, Hasnain S, Lucke AJ, Fairlie DP, McGuckin MA, Florin TH, Begun J. Cell Mol Gastroenterol Hepatol 2021,11, 33-53.
PAR2-induced tissue factor synthesis by primary cultures of human kidney tubular epithelial cells is modified by glucose availability. Humphries TLR, Shen K, Iyer A, Johnson DW, Gobe GC, Nikolic-Paterson D, Fairlie DP, Vesey DA. Int J Mol Sci 2021, 22, 7532.
Mechanotransduction activates RhoA in the neighbors of apoptotic epithelial cells to engage apical extrusion. Duszyc K, Gomez GA, Lagendijk AK, Yau MK, Nanavati BN, Gliddon BL, Hall TE, Verma S, Hogan BM, Pitson SM, Fairlie DP, Parton RG, Yap AS. Curr Biol 2021, 31, 1326-1336.e5.
PAR2 induces ovarian cancer cell motility by merging three signalling pathways to transactivate EGFR. Jiang Y, Lim J, Wu KC, Xu W, Suen JY, Fairlie DP. Br J Pharmacol 2021, 178, 913-932.
2020
The molecular basis underpinning the potency and specificity of MAIT cell antigens. Awad W, Ler G, Xu W, Keller AN, Mak JYW, Yi X, Lim J, Liu L, Eckle SBG, Le Nours J, McCluskey J, Corbett AJ, Fairlie DP, Rossjohn J. Nat Immunol 2020, 21, 400-411.
Potent thiophene antagonists of human complement C3a receptor with anti-inflammatory activity. Rowley JA, Reid RC, Poon EKY, Wu KC, Lim J, Lohman RJ, Hamidon JK, Yau MK, Halili MA, Durek T, Iyer A, Fairlie DP. J Med Chem 2020, 63, 529-541.
MAIT cells promote tumor initiation, growth, and metastases via tumor MR1. Yan J, Allen S, McDonald E, Das I, Mak JYW, Liu L, Fairlie DP, Meehan BS, Chen Z, Corbett AJ, Varelias A, Smyth MJ, Teng MWL. Cancer Discov 2020, 10, 124-141.
2019
Diverse MR1-restricted T cells in mice and humans. Koay HF, Gherardin NA, Xu C, Seneviratna R, Zhao Z, Chen Z, Fairlie DP, McCluskey J, Pellicci DG, Uldrich AP, Godfrey DI. Nat Commun. 2019,10, 2243.
Inhibitors of class I histone deacetylases attenuate thioacetamide-induced liver fibrosis in mice by suppressing hepatic type 2 inflammation. Loh Z, Fitzsimmons RL, Reid RC, Ramnath D, Clouston A, Gupta PK, Irvine KM, Powell EE, Schroder K, Stow JL, Sweet MJ, Fairlie DP, Iyer A. Br J Pharmacol. 2019, 176, 3775-3790.
A class of γδ T cell receptors recognize the underside of the antigen-presenting molecule MR1. Le Nours J, Gherardin NA, Ramarathinam SH, Awad W, Wiede F, Gully BS, Khandokar Y, Praveena T, Wubben JM, Sandow JJ, Webb AI, von Borstel A, Rice MT, Redmond SJ, Seneviratna R, Sandoval-Romero ML, Li S, Souter MNT, Eckle SBG, Corbett AJ, Reid HH, Liu L, Fairlie DP, Giles EM, Westall GP, Tothill RW, Davey MS, Berry R, Tiganis T, McCluskey J, Pellicci DG, Purcell AW, Uldrich AP, Godfrey DI, Rossjohn J. Science 2019, 366(6472),1522-1527.
IL-23 costimulates antigen-specific MAIT cell activation and enables vaccination against bacterial infection. Wang H, Kjer-Nielsen L, Shi M, D'Souza C, Pediongco TJ, Cao H, Kostenko L, Lim XY, Eckle SBG, Meehan BS, Zhu T, Wang B, Zhao Z, Mak JYW, Fairlie DP, Teng MWL, Rossjohn J, Yu D, de St Groth BF, Lovrecz G, Lu L, McCluskey J, Strugnell RA, Corbett AJ, Chen Z. Sci Immunol 2019, 4(41). pii: eaaw0402.
Protease-activated receptor 2 does not contribute to renal inflammation or fibrosis in the obstructed kidney. Ma FY, Han Y, Ozols E, Chew P, Vesey DA, Gobe GC, Morais C, Lohman RJ, Suen JY, Johnson DW, Fairlie DP, Nikolic-Paterson DJ. Nephrology (Carlton). 2019, 24, 983-991.
Structure-activity relationships of Wollamide cyclic hexapeptides with activity against drug-resistant and intracellular mycobacterium tuberculosis. Khalil ZG, Hill TA, De Leon Rodriguez LM, Lohman RJ, Hoang HN, Reiling N, Hillemann D, Brimble MA, Fairlie DP, Blumenthal A, Capon RJ. Antimicrob Agents Chemother 2019, 63(3), pii: e01773-18.
A divergent transcriptional landscape underpins the development and functional branching of MAIT cells. Koay HF, Su S, Amann-Zalcenstein D, Daley SR, Comerford I, Miosge L, Whyte CE, Konstantinov IE, d'Udekem Y, Baldwin T, Hickey PF, Berzins SP, Mak JYW, Sontani Y, Roots CM, Sidwell T, Kallies A, Chen Z, Nüssing S, Kedzierska K, Mackay LK, McColl SR, Deenick EK, Fairlie DP, McCluskey J, Goodnow CC, Ritchie ME, Belz GT, Naik SH, Pellicci DG, Godfrey DI. Sci Immunol 2019, 4(41). pii: eaay6039.
MAIT Cells Upregulate α4β7 in Response to Acute Simian Immunodeficiency Virus/Simian HIV Infection but Are Resistant to Peripheral Depletion in Pigtail Macaques. Juno JA, Wragg KM, Amarasena T, Meehan BS, Mak JYW, Liu L, Fairlie DP, McCluskey J, Eckle SBG, Kent SJ. J Immunol. 2019, 202, 2105-2120.
Oxazole-benzenesulfonamide derivatives inhibit HIV-1 reverse transcriptase interaction with cellular eEF1A and reduce viral replication. Rawle DJ, Li D, Wu Z, Wang L, Choong M, Lor M, Reid RC, Fairlie DP, Harris J, Tachedjian G, Poulsen SA, Harrich D. J Virol 2019, 93(12), pii: e00239-19.
Computer modelling and synthesis of deoxy and monohydroxy analogues of a ribitylaminouracil bacterial metabolite that potently activates human T cells. Ler GJM, Xu W, Mak JYW, Liu L, Bernhardt PV. Fairlie DP. Chemistry. 2019, 25, 15594-15608.
Characterization of Human Mucosal-associated Invariant T (MAIT) Cells. Souter MNT, Loh L, Li S, Meehan BS, Gherardin NA, Godfrey DI, Rossjohn J, Fairlie DP, Kedzierska K, Pellicci DG, Chen Z, Kjer-Nielsen L, Corbett AJ, McCluskey J, Eckle SBG. Curr Protoc Immunol 2019, 127(1), e90.
Characterization and Purification of Mouse Mucosal-Associated Invariant T (MAIT) Cells. Chen Z, Wang H, D'Souza C, Koay HF, Meehan B, Zhao Z, Pediongco T, Shi M, Zhu T, Wang B, Kjer-Nielsen L, Eckle SBG, Rossjohn J, Fairlie DP, Godfrey DI, Strugnell RA, McCluskey J, Corbett AJ. Curr Protoc Immunol 2019,127(1), e89.
2018
Recipient mucosal-associated invariant T cells control GVHD within the colon. Varelias A, Bunting MD, Ormerod KL, Koyama M, Olver SD, Straube J, Kuns RD, Robb RJ, Henden AS, Cooper L, Lachner N, Gartlan KH, Lantz O, Kjer-Nielsen L, Mak JY, Fairlie DP, Clouston AD, McCluskey J, Rossjohn J, Lane SW, Hugenholtz P, Hill GR. J Clin Invest 2018, 128, 1919-1936.
Chemical Approaches to Modulating Complement-Mediated Diseases. Iyer A, Xu W, Reid RC, Fairlie DP. J Med Chem 2018, 61, 3253-3276.
Lysine Deacetylases and Regulated Glycolysis in Macrophages. Shakespear MR, Iyer A, Cheng CY, Das Gupta K, Singhal A, Fairlie DP, Sweet MJ. Trends Immunol 2018, 39, 473-488.
Mucosal-associated invariant T cells augment immunopathology and gastritis in chronic Helicobacter pylori Infection. D'Souza C, Pediongco T, Wang H, Scheerlinck JY, Kostenko L, Esterbauer R, Stent AW, Eckle SBG, Meehan BS, Strugnell RA, Cao H, Liu L, Mak JYW, Lovrecz G, Lu L, Fairlie DP, Rossjohn J, McCluskey J, Every AL, Chen Z, Corbett AJ. J Immunol 2018, 200, 1901-1916.
A potent antagonist of protease-activated receptor 2 that inhibits multiple signalling functions in human cancer cells.Jiang Y, Yau MK, Lim J, Wu KC, Xu W, Suen JY, Fairlie DP. J Pharmacol Exp Ther 2018, 364, 246-257.
Enumeration, functional responses and cytotoxic capacity of MAIT cells in newly diagnosed and relapsed multiple myeloma. Gherardin NA, Loh L, Admojo L, Davenport AJ, Richardson K, Rogers A, Darcy PK, Jenkins MR, Prince HM, Harrison SJ, Quach H, Fairlie DP, Kedzierska K, McCluskey J, Uldrich AP, Neeson PJ, Ritchie DS, Godfrey DI. Sci Rep 2018, 8, 4159.
Human blood MAIT cell subsets defined using MR1 tetramers. Gherardin NA, Souter MN, Koay HF, Mangas KM, Seemann T, Stinear TP, Eckle SB, Berzins SP, d'Udekem Y, Konstantinov IE, Fairlie DP, Ritchie DS, Neeson PJ, Pellicci DG, Uldrich AP, McCluskey J, Godfrey DI. Immunol Cell Biol 2018, 96, 507-525.
An overview on the identification of MAIT cell antigens. Kjer-Nielsen L, Corbett AJ, Chen Z, Liu L, Mak JYW, Godfrey DI, Rossjohn J, Fairlie DP, McCluskey J, Eckle SBG. Immunol Cell Biol 2018, 96, 573-587.
Complement C3a and C5a receptors promote GVHD by suppressing mitophagy in recipient dendritic cells. Nguyen H, Kuril S, Bastian D, Kim J, Zhang M, Vaena SG, Dany M, Dai M, Heinrichs JL, Daenthanasanmak A, Iamsawat S, Schutt S, Fu J, Wu Y, Fairlie DP, Atkinson C, Ogretmen B, Tomlinson S, Yu XZ. JCI Insight 2018, 3(24), pii: 121697.
Lysine deacetylases and regulated glycolysis in macrophages. Shakespear MR, Iyer A, Cheng CY, Das Gupta K, Singhal A, Fairlie DP, Sweet MJ.Trends Immunol 2018, 39, 473-488.
Hepatic expression profiling identifies steatosis-independent and steatosis-driven advanced fibrosis genes. Ramnath D, Irvine KM, Lukowski SW, Horsfall LU, Loh Z, Clouston AD, Patel PJ, Fagan KJ, Iyer A, Lampe G, Stow JL, Schroder K, Fairlie DP, Powell JE, Powell EE, Sweet MJ. JCI Insight 2018, 3(14), pii: 120274.
MAIT cells protect against pulmonary Legionella longbeachae infection. Wang H, D'Souza C, Lim XY, Kostenko L, Pediongco TJ, Eckle SBG, Meehan BS, Shi M, Wang N, Li S, Liu L, Mak JYW, Fairlie DP, Iwakura Y, Gunnersen JM, Stent AW, Godfrey DI, Rossjohn J, Westall GP, Kjer-Nielsen L, Strugnell RA, McCluskey J, Corbett AJ, Hinks TSC, Chen Z. Nat Commun 2018, 9, 3350.
2017
Exploiting a novel conformational switch to control innate immunity mediated by complement protein C3a. Lohman R-J, Hamidon JK, Reid RC, Rowley JA, Yau M-K, Halili MA, Nielsen DS, Lim J, Wu K-C, Loh Z, Do A, Suen JY, Iyer A, Fairlie DP. Nature Commun 2017, 8, 351.
Stabilising short-lived Schiff base derivatives of 5-aminouracils that activate mucosal-associated invariant T cells. Mak JYW, Xu W, Reid RC, Corbett AJ, Meehan B, Wang H, Chen Z, Rossjohn J, McCluskey J, Liu L, Fairlie DP. Nature Commun 2017, 8, 14599.
Drugs and drug-like molecules can modulate the function of mucosal-associated invariant T cells. Keller AN, Eckle SBG, Xu W, Liu L, Hughes VA, Mak JYW, Meehan B, Pediongco T, Birkinshaw RW, Chen Z, Wang H, D’Souza C, Kjer-Nielsen L, Gheradin NA, Godfrey DI, Kostenko L, Corbett AJ, Purcell AW, Fairlie DP*, McCluskey J*, Rossjohn J*. Nature Immunology 2017, 18, 402-411.
The ribosomal protein S19 suppresses antitumor immune responses via the complement C5a receptor 1. Vadrevu SK, Sharma SK, Chintala NK, Cho J-H, Patel J, Patel B, Fairlie DP, Paterson Y, Astrinidis A, Karbowniczek M, Markiewski MM. J Immunol 2017, 198, 2989-2999.
Mucosal-associated invariant T cell activation and accumulation after in vivo infection depends on microbial riboflavin synthesis and co-stimulatory signals. Chen Z, Wang H, D’Souza C, Sun S, Kostenko L, Eckle SBG, Meehan BS, Jackson DC, Strugnell RA, Cao H, Wang N, Fairlie DP, Liu L, Godfrey DI, Rossjohn J, McCluskey J, Corbett AJ. Mucosal Immunology 2017, 10: 58-68.
Europium-Labeled Synthetic C3a Protein as a Novel Fluorescent Probe for Human Complement C3a Receptor. de Araujo AD, Wu C, Wu KC, Reid RC, Durek T, Lim J, Fairlie DP. Bioconjug Chem 2017, 28, 1669-1676.
Total synthesis of the Mycobacterium tuberculosis dideoxymycobactin-838 and stereoisomers: Diverse CD1a-restricted T cells display a common hierarchy of lipopeptide recognition. Cheng JMH, Liu L, Pellicci DG, Reddiex S, Cotton RN, Cheng T-Y, Young DC, Van Rhijn I, Moody DB, Rossjohn J, Fairlie DP*, Godfrey DI*, Williams SJ*. Chem Eur J 2017, 23, 1694-1701.
An HDAC6 inhibitor confers protection and selectively inhibits B-cell infiltration in DSS-induced colitis in mice. Do A, Reid RC, Lohman RJ, Sweet MJ, Fairlie DP*, Iyer A*. J Pharmacol Exp Ther 2017, 360, 140-151.
Protease activated receptor 2 controls myelin development, resiliency and repair. Yoon H, Radulovic M, Walters G, Paulsen AR, Drucker K, Starski P, Wu J, Fairlie DP, Scarisbrick IA. Glia 2017, 65, 2070-2086.
2016
Inhibition of membrane-anchored serine protease matriptase reduces experimental pulmonary fibrosis. Bardou O, François C, Menou A, Jvon der Thüsen J, Borie R, Castier Y, Sage E, Liu L, Fairlie DP, Königshoff M, Crestani B, Borensztajn K. American Journal of Respiratory and Critical Care Medicine, 2016, 193, 847-860.
Diversity of T Cells Restricted by the MHC Class I-Related Molecule MR1 Facilitates Differential Antigen Recognition. Gherardin NA, Keller AN, Woolley RE, Le Nours J, Ritchie DS, Neeson PJ, Birkinshaw RW, Eckle SB, Waddington JN, Liu L, Fairlie DP, Uldrich AP, Pellicci DG, McCluskey J, Godfrey DI, Rossjohn J. Immunity 2016, 44, 32-45. ISI Highly Cited.
The intracellular pathway for the presentation of vitamin B-related antigens by the antigen-presenting molecule MR1. McWilliam HEG, Eckle SBG, Theodossis A, Liu L, Chen Z, Wubben JM, Fairlie DP, Strugnell RA, Mintern JD, McCluskey J, Rossjohn J, Villadangos JA. Nature Immunol 2016, 17, 531-537.
A three-stage intrathymic development pathway for the mucosal-associated invariant T cell lineage. Koay HF, Gherardin NA, Enders A, Loh L, Mackay LK, Almeida CF, Russ BE, Nold-Petry CA, Nold MF, Bedoui S, Chen Z, Corbett AJ, Eckle SB, Meehan B, d'Udekem Y, Konstantinov IE, Lappas M, Liu L, Goodnow CC, Fairlie DP, Rossjohn J, Chong MM, Kedzierska K, Berzins SP, Belz GT, McCluskey J, Uldrich AP, Godfrey DI, Pellicci DG. Nature Immunol 2016, 17, 1300-1311.
Receptor residence time trumps drug-likeness and oral bioavailability in determining efficacy of complement C5a antagonists. Seow V, Lim J, Cotterell AJ, Yau MK, Xu W, Lohman RJ, Kok WM, Stoermer MJ, Sweet MJ, Reid RC, Suen JY, Fairlie DP. Science Reports 2016, 6, 24575.
Differential Anti-inflammatory Activity of HDAC Inhibitors in Human Macrophages and Rat Arthritis. Lohman RJ, Iyer A, Fairlie TJ, Cotterell A, Gupta P, Reid RC, Vesey DA, Sweet MJ, Fairlie DP. J Pharmacol Exp Ther 2016, 356, 387-396.
Histone deacetylase inhibitors promote mitochondrial reactive oxygen species production and bacterial clearance by human macrophages. Ariffin JK, das Gupta K, Kapetanovic R, Iyer A, Reid RC, Fairlie DP, Sweet MJ. Antimicrob Agents Chemother 2016, 60, 1521-1529.
Antagonism Of The Proinflammatory And Pronociceptive Actions Of Canonical And Biased Agonists Of Protease Activated Receptor 2. Lieu T, Savage E, Zhao P, Edgington-Mitchell L, Barlow N, Bron R, Poole DP, McLean P, Lohman RJ, Fairlie DP, Bunnett NW. Br J Pharmacol 2016, 173, 2752-2765.
Human mucosal-associated invariant T cells contribute to antiviral influenza immunity via IL-18-dependent activation. Loh L, Wang Z, Sant S, Koutsakos M, Jegaskanda S, Corbett AJ, Liu L, Fairlie DP, Crowe J, Rossjohn J, Xu J, Doherty PC, McCluskey J, Kedzierska K. Proc Natl Acad Sci USA 2016, 113, 10133-10138.
Benzylamide antagonists of protease activated receptor 2 with anti-inflammatory activity. Yau MK, Liu L, Lim J, Lohman RJ, Cotterell AJ, Suen JY, Vesey DA, Reid RC, Fairlie DP. Bioorg Med Chem Lett 2016, 25, 5604-5608.
Histone deacetylases in monocyte/macrophage development, activation and metabolism: refining HDAC targets for inflammatory and infectious diseases. Das Gupta K, Shakespear MR, Iyer A, Fairlie DP, Sweet MJ. Clin Transl Immunology 2016, 5(1), e62.
2015
Nutrient and immune sensing are obligate pathways in metabolism, immunity, and disease. Iyer A, Brown L, Whitehead JP, Prins JB, Fairlie DP. FASEB J 2015, 29, 3612-3625.
Functional Heterogeneity and Antimycobacterial Effects of Mouse Mucosal-Associated Invariant T Cells Specific for Riboflavin Metabolites. Sakala IG, Kjer-Nielsen L, Eickhoff CS, Wang X, Blazevic A, Liu L, Fairlie DP, Rossjohn J, McCluskey J, Fremont DH, Hansen TH, Hoft DF. J Immunol 2015, 195, 587-601.
Identification of phenotypically and functionally heterogeneous mouse mucosal-associated invariant T cells using MR1 tetramers. Rahimpour A, Koay HF, Enders A, Clanchy R, Eckle SB, Meehan B, Chen Z, Whittle B, Liu L, Fairlie DP, Goodnow CC, McCluskey J, Rossjohn J, Uldrich AP, Pellicci DG, Godfrey DI. J Exp Med 2015, 212, 1095-1108.
Inhibiting histone deacetylase 1 suppresses both inflammation and bone loss in arthritis. Cantley MD, Fairlie DP, Bartold PM, Marino V, Gupta PK, Haynes DR. Rheumatology (Oxford) 2015, 54, 1713-1723.
Recognition of Vitamin B precursors and byproducts by Mucosal Associated Invariant T cells. Eckle SB, Corbett AJ, Keller A, Chen Z, Godfrey DI, Liu L, Mak JY, Fairlie DP, Rossjohn J, McCluskey J. J Biol Chem 2015, 290, 30204-30211.
Singh R, Reed AN, Chu P, Scully CC, Yau MK, Suen JY, Durek T, Reid RC, Fairlie DP. Potent complement C3a receptor agonists derived from oxazole amino acids: Structure-activity relationships. Bioorg Med Chem Lett 2015, 25, 5604-5608.
2014
Complement C5a receptor facilitates cancer metastasis by altering T cell responses in the metastatic niche. Vadrevu SK, Chintala NK, Sharma SK, Sharma P, Cleveland C, Riediger L, Manne S, Fairlie DP, Gorczyca W, Almanza O, Karbowniczek M, Markiewski MM. Cancer Research 2014, 74, 3454-3465.
T cell activation by transitory neo-antigens derived from distinct microbial pathways. Corbett AJ, Eckle SBG, Birkinshaw RW, Liu L, Patel O, Mahony J, Chen Z, Reantra-goon R, Meehan B, Cao H, Williamson NA, Strugnell RA, Sinderen DV, Mak JYW, Fairlie DP*, Kjer-Nielsen L*, Rossjohn J*, McCluskey J*. Nature 2014, 509(7500), 361-365. ISI Highly Cited. [>100 cites]
Biased Signalling and Proteinase-Activated Receptors (PARs): Targeting Inflammatory Disease. Hollenberg MD, Mihara K, Polley D, Suen JY, Han A, Fairlie DP, Ramachandran R. Br J Pharmacol. 2014, 171, 1180-1194. ISI Highly Cited.
Pathway Selective Antagonism Of Proteinase Activated Receptor 2. Suen JY, Cotterell A, Lohman RJ, Han A, Yau MK, Liu L, Cooper MA, Vesey DA, Fairlie DP. Br J Pharmacol 2014, 171, 4112-4124.
C5aR and C5L2 act in concert to balance immunometabolism in adipose tissue. Poursharifi P, Lapointe M, Fisette A, Lu H, Roy C, Munkonda MN, Fairlie DP, Cianflone K. Molecular and Cellular Endocrinology 2014, 382, 325-333.
A Molecular Basis Underpinning the T Cell Heterogeneity of Mucosal Associated Invariant T Cells. Eckle SBG, Birkinshaw RW, Kostenko L, Corbett AJ, McWilliam HEG, Reantragoon R, Chen Z, Gherardin NA, Beddoe T, Liu L, Patel O, Meehan B, Fairlie DP, Villadangos JA, Godfrey DI, Kjer-Nielsen L, McCluskey J, Rossjohn J. J Exp Med 2014, 211, 1585-1600.
Potent Heterocyclic Ligands for Human Complement C3a Receptor. Reid RC, Yau M-K, Singh R, Hamidon JK, Lim J, Stoermer MJ, Fairlie DP. J Med Chem 2014, 57, 8459-8470.
Stereoelectronic effects dictate molecular conformation and biological function of heterocyclic amides. Reid RC, Yau MK, Singh R, Lim J, Fairlie DP. J Am Chem Soc 2014, 136, 11914-11917. Faculty1000Prime.
Helical cyclic pentapeptides constrain HIV-1 Rev peptide for enhanced RNA binding. Harrison RS, Shepherd NE, Hoang HN, Beyer RL, Ruiz-Gómez G, Kelso MJ, WM Kok, TA Hill, Abbenante G, Fairlie DP. Tetrahedron 2014, 70, 7645-7650 [special issue on cyclic peptides].
2013
Inflammatory responses induced by lipopolysaccharide are amplified in primary human monocytes but suppressed in macrophages by complement protein C5a. Seow V, Lim J, Iyer A, Suen JY, Ariffin JK, Hohenhaus DM, Sweet MJ, Fairlie DP. J Immunol 2013, 191, 4308-4316.
Diet-Induced Obesity, Adipose Tissue Inflammation And Metabolic Dysfunction Correlating With PAR2 Expression Are Attenuated By A PAR2 Antagonist. Lim J, Iyer A, Suen JY, Liu L, Lohman RJ, Seow V, Yau MK, Brown L, Fairlie DP. FASEB J 2013, 27, 4757-4767.
Downsizing a Human Inflammatory Protein to a Small Molecule with Equal Potency and Functionality. Reid RC, Yau M-K, Singh R, Hamidon JK, Reed AN, Chu P, Suen JY, Stoermer MJ, Blakeney JS, Lim J, Faber JM, Fairlie DP. Nature Communications 2013, 4, 2802. doi:10.1038/ncomms3802.
C5aR and C3aR antagonists each inhibit diet-induced obesity, metabolic dysfunction, and adipocyte and macrophage signaling. Lim J, Iyer A, Suen JY, Seow V, Reid RC, Brown L, Fairlie DP. FASEB J 2013, 27, 822-831.
Antigen-loaded MR1 tetramers define T cell receptor heterogeneity in Mucosal-Associated Invariant T-cells. Reantragoon R, Corbett AJ, Sakala IG, Gherardin NA, Furness JB, Birkinshaw R, Chen Z, Patel O, Kostenko L, Meehan B, Eckle SBG, Kedzierska K, Pellicci D, Liu L, Fairlie DP, Godfrey DI, Hansen TH, Kjer-Nielsen L, Rossjohn J, McCluskey J. J Exp Med 2013, 210, 2305-2320. [>100 cites]
An mRNA atlas of G protein-coupled receptor expression during primary human monocyte/macrophage differentiation and lipopolysaccharide-mediated activation identifies targetable candidate regulators of inflammation. Hohenhaus DM, Schaale K, Le Cao KA, Seow V, Iyer A, Fairlie DP, Sweet MJ. Immunobiology 2013, 218, 1345-1353.
Histone deacetylase 7 promotes Toll-like Receptor 4-dependent pro-inflammatory gene expression in macrophages. Shakespear MR, Hohenhaus DM, Kelly GM, Kamal NA, Gupta P, Labzin LI, Schroder K, Garceau V, Barbero S, Iyer A, Hume DA, Reid RC, Irvine KM, Fairlie DP, Sweet MJ. J Biol Chem 2013, 288, 25362-2537271.
Recognition of vitamin B metabolites by mucosal-associated invariant T cells. Patel O, Kjer-Nielsen L, Nours JL, Eckle SBG, Bikinshaw R, Beddoe T, Corbett AJ, Liu L, Miles JJ, Mehan B, Reantragoon R, Sandoval-Romero ML, Sullivan LC, Brooks AG, Chen Z, Fairlie DP, McCluskey J, Rossjohn J. Nature Commun 2013, 4, 2142. doi: 10.1038/ncomms3142.
Toward Drugs for Protease-Activated Receptor 2 (PAR2). Yau MK, Liu L, Fairlie DP. J Med Chem 2013, 56, 7477-7497.
Efficient chemical synthesis of human complement protein C3a. Ghassemian A, Wang CI, Yau MK, Reid RC, Lewis RJ, Fairlie DP, Alerwood PF, Durek T. Chem Commun 2013, 49, 2356-2358.
PAR2-induced inflammatory responses in human kidney tubular epithelial cells. Vesey DA, Suen JY, Seow V, Lohman RJ, Liu L, Gobe GC, Johnson DW, Fairlie DP. Am J Physiol Renal Physiol. 2013, 304(6), F737-750.
2012
MR1 presents microbial vitamin B metabolites to MAIT cells. Kjer-Nielsen L, Patel O, Nours JL, Meehan B, Corbett AJ, Liu L, Bhati M, Chen Z, Kostenko L, Reantragoon R, Williamson NA, Purcell AW, Dudek NL, McConville MJ, O’Hair RAJ, Khairallah GN, Godfrey DI, Fairlie DP, Rossjohn J, McCluskey J. Nature 2012, 491, 717-723. ISI Highly Cited. [>100 cites]
An antagonist of human protease activated receptor-2 attenuates PAR2 signaling, macrophage activation, mast cell degranulation, and collagen-induced arthritis in rats. Lohman RJ, Cotterell AJ, Barry GD, Liu L, Suen JY, Vesey DA, Fairlie DP. FASEB J. 2012, 26, 2877-2887.
Antagonism of protease-activated receptor 2 protects against experimental colitis. Lohman RJ, Cotterell AJ, Suen J, Liu L, Do AT, Vesey DA, Fairlie DP. J Pharmacol Exp Ther 2012, 340, 256-265.
Modulating human proteinase activated receptor 2 with a novel antagonist (GB88) and agonist (GB110). Suen JY, Barry GD, Lohman RJ, Halili MA, Cotterell AJ, Le GT, Fairlie DP. Br J Pharmacol 2012, 165, 1413-1423.
Histone deacetylase inhibitors as suppressors of bone destruction in inflammatory diseases. Cantley MD, Bartold PM, Fairlie DP, Rainsford KD, Haynes DR. J Pharm Pharmacol 2012, 64, 763-774.
C5a receptor (CD88) inhibition improves hypothermia-induced neuroprotection in an in vitro ischemic model. Thundyil J, Pavlovski D, Hsieh YH, Gelderblom M, Magnus T, Fairlie DP, Arumugam TV. Neuromolecular Med. 2012, 14, 30-39.
Lysine acetylation in obesity, diabetes and metabolic disease. Iyer A, Fairlie DP, Brown L. Immunol Cell Biol 2012, 90, 39-46.
HDAC inhibitors: modulating leukocyte differentiation, survival, proliferation and inflammation. Sweet MJ, Shakespear MR, Kamal NA, Fairlie DP. Immunol Cell Biol 2012, 90, 14-22.
Some Previous Examples
Histone deacetylases as regulators of inflammation and immunity. Shakespear MR, Halili MA, Irvine KM, Fairlie DP, Sweet MJ. Trends Immunol 2011, 32, 335-343. [>100 cites]
Structure, function and pathophysiology of protease activated receptors. Adams MN, Ramachandran R, Yau MK, Suen JY, Fairlie DP, Hollenberg MD, Hooper JD. Pharmacol Ther 2011, 130, 248-282. [>100 cites] ISI Highly Cited.
Antifibrotic activity of an inhibitor of histone deacetylases in DOCA-salt hypertensive rats. Iyer A, Fenning A, Lim J, Le GT, Reid RC, Halili MA, Fairlie DP, Brown L. Br J Pharmacol 2010, 159, 1408-1417.
Inflammatory lipid mediators in adipocyte function and obesity. Iyer A, Fairlie DP, Prins J, Hammock BD, Brown L.
