Prof Charles Mackay - Researcher Profile

Charles Mackay

Address

Monash Immunology & Stem Cell Labs
Faculty of Medicine, Nursing & Health Sciences, Clayton

Contact Details

Tel: +61 3 990 29510

Email: Charles.Mackay@monash.edu


Biography

Developing treatments to fight inflammatory disease

Eminent immunologist Professor Charles Mackay is testing therapies to revolutionise the treatment of inflammatory diseases such as rheumatoid arthritis and asthma. At the same time, he is launching new research to unravel the links between diet and inflammatory diseases.

Charles has received international recognition for major breakthroughs in understanding the role of white blood cells and how they move around the body. This work also led to new understanding on how Human Immunodeficiency Virus (HIV) infects cells. His more recent research into inflammatory diseases has resulted in the development of a new antibody treatment, now in human clinical trials for rheumatoid arthritis.

“There are a huge number of inflammatory diseases. For instance, there are 50 or more auto-immune type diseases, where the immune system attacks the body’s own organs,” Charles says. “MS, inflammatory bowel disease, psoriasis, lupus, rheumatoid arthritis and allergic diseases like asthma, septic shock and transplantation rejection, all may be managed more effectively if the antibodies we’re testing prove effective.

“Producing a drug that inhibits inflammatory diseases would benefit human health enormously. It would be a very big deal for Australia and obviously for me,” he says.

The interaction between the body’s immune and metabolic systems is another major area of research that Charles is leading as head of Monash University’s Centre for Immunology and Inflammation at Clayton. 

“This is an exciting area for us. People perhaps haven’t totally appreciated how connected these major systems are. They influence one another. The microbes that colonise our intestinal tract are a part of this mix. Understanding how diet and the metabolism of dietary substances affect gut microbes and how they affect our immune system is a brand new direction in medical research.”

He says the prevailing theory for diseases such as asthma is the hygiene hypothesis. The overuse of soaps and antibiotics means Western society is too clean and people are not exposed to enough infections to properly train their immune systems.

“We don’t subscribe to that. We think the incidence of diabetes, asthma and auto-immune diseases in Western countries like Australia, the USA and Europe relate to a changing diet. Reduced fibre and fish, increased processed foods and resulting obesity has altered the mix of microbes and the things they produce. All this changes our immune system, and we believe this is what causes asthma, Type 1 diabetes and other diseases.”

Charles believes this research could take years to unravel. It will require long-term epidemiological studies. He compares it to the days when cigarette smoke was first suspected of causing cancer. “You get an inkling that something’s there and you begin to unravel the molecules involved. In the end you need large studies with clinical samples and patients over many years.

“For example, asthma can take some years to develop in a child. You don’t know when it was set in place, whether in the womb or early years of life. So I suspect it will be five to 10 years before we understand the true impact of diet.”

He says immunologists in the past did not give much credence to prebiotics (beneficial foodstuffs) and probiotics (beneficial microbes) as affecting immune function and inflammatory diseases. These concepts were regarded as being on the fringe of acceptable science. “That’s partly because scientists like to see the molecular mechanisms before they will fully accept new ideas. If you have a phenomenon or an observation and can marry that with a molecule and genes, then you can see the entire picture.”

Keywords

T-cell migration, expression of chemokine receptors , immunology and inflammation

Qualifications

PH.D - VET SCIENCE
Institution: Melbourne University
Year awarded: 1986
BSC. (HONS)
Institution: Monash University
Year awarded: 1980

Publications

Journal Articles

Chtanova, T., Hampton, H.R., Waterhouse, L.A., Woods, K., Tomura, M., Miwa, Y., Mackay, C.R., Brink, R., Phan, T.G., 2013, Real-time interactive two-photon photoconversion of recirculating lymphocytes for discontinuous cell tracking in live adult mice, Journal of Biophotonics [P], vol E-pub, Wiley - V C H Verlag GmbH & Co. KGaA, Germany, pp. 1-9.

Marino, E., Tan, B., Binge, L.C., Mackay, C.R., Grey, S.T., 2012, B-cell cross-presentation of autologous antigen precipitates diabetes, Diabetes [P], vol 61, issue 11, American Diabetes Association, USA, pp. 2893-2905.

Starkey, M.R., Kim, R.Y., Beckett, E.L., Schilter, H.C., Shim, D.S., Essilfie, A., Nguyen, D.H., Beagley, K.W., Mattes, J., Mackay, C.R., Horvat, J.C., Hansbro, P.M., 2012, Chlamydia muridarum lung infection in infants alters hematopoietic cells to promote allergic airway disease in mice, PLoS ONE [P], vol 7, issue 8 (Art. No.: 42588), Public Library of Science, USA, pp. 1-7.

Bansal, R.R., Mackay, C.R., Moser, B., Eberl, M., 2012, IL-21 enhances the potential of human {gamma delta} T cells to provide B-cell help, European Journal Of Immunology [P], vol 42, issue 1, Wiley - V C H Verlag GmbH & Co. KGaA, Germany, pp. 110-119.

Gunton, J.E., Sisavanh, M., Stokes, R.A., Satin, J., Satin, L.S., Zhang, M., Liu, S.M., Cai, W., Cheng, K., Cooney, G.J., Laybutt, D.R., So, T., Molero, J., Grey, S.T., Andres, D.A., Rolph, M.S., Mackay, C.R., 2012, Mice deficient in GEM GTPase show abnormal glucose homeostasis due to defects in beta-cell calcium handling, PLoS ONE [P], vol 7, issue 6 (Art. No: e39462), Public Library of Science, USA, pp. 1-9.

Macia, L., Thorburn, A.N., Binge, L.C., Marino Moreno, E., Rogers, K.E., Maslowski, K.M., Vieira, A.T., Kranich, J., Mackay, C.R., 2012, Microbial influences on epithelial integrity and immune function as a basis for inflammatory diseases, Immunological Reviews [P], vol 245, issue 1, Wiley-Blackwell Publishing Inc., USA, pp. 164-176.

Shim, D.S., Schilter, H.C., Knott, M.L., Almeida, R.A., Short, R.P., Mackay, C.R., Dent, L.A., Sewell, W.A., 2012, Protection against Nippostrongylus brasiliensis infection in mice is independent of GM-CSF, Immunology And Cell Biology [P], vol 90, issue 5, Nature Publishing Group, UK, pp. 553-558.

Chevalier, N., Jarrossay, D., Ho, E., Avery, D.T., Ma, C.S., Yu, D., Sallusto, F., Tangye, S.G., Mackay, C.R., 2011, CXCR5 expressing human central memory CD4 T cells and their relevance for humoral immune responses, Journal Of Immunology [P], vol 186, issue 10, American Association of Immunologists, USA, pp. 5556-5568.

Kranich, J., Maslowski, K.M., Mackay, C.R., 2011, Commensal flora and the regulation of inflammatory and autoimmune responses, Seminars In Immunology [P], vol 23, issue 2, Academic Press, UK, pp. 139-145.

Fletcher, C., Groom, J., Woehl, B., Leung, H., Mackay, C., Mackay-Fisson, F., 2011, Development of autoimmune nephritis in genetically asplenic and splenectomized BAFF transgenic mice, Journal Of Autoimmunity [P], vol 36, issue 2, Academic Press, United Kingdom, pp. 125-134.

Maslowski, K.M., Mackay, C.R., 2011, Diet, gut microbiota and immune responses, Nature Immunology [P], vol 12, issue 1, Nature Publishing Group, USA, pp. 5-9.

Santos, L., Fan, H., Hall, P., Ngo, D., Mackay, C., Fingerle-Rowson, G., Bucala, R., Hickey, M., Morand, E., 2011, Macrophage migration inhibitory factor regulates neutrophil chemotactic responses in inflammatory arthritis in mice, Arthritis & Rheumatism-Arthritis Care & Research [P], vol 63, issue 4, John Wiley & Sons, Inc., USA, pp. 960-970.

Kolbeck, R., Kozhich, A., Koike, M., Peng, L., Andersson, C.K., Damschroder, M.M., Reed, J.L., Woods, R., Dall'Acqua, W.W., Stephens, G.L., Erjefalt, J.S., Bjermer, L., Humbles, A.A., Gossage, D., Wu, H., Kiener, P.A., Spitalny, G.L., Mackay, C., Molfino, N.A., Coyle, A.J., 2010, MEDI-563, a humanized anti-IL-5 receptor alpha mAb with enhanced antibody-dependent cell-mediated cytotoxicity function, Journal Of Allergy And Clinical Immunology [P], vol 125, issue 6, Mosby Inc, USA, pp. 1344-1353.e2.

Bamberg, C.E., Mackay, C., Lee, H., Zahra, D., Jackson, J., Lim, Y.S., Whitfeld, P.L., Craig, S., Corsini, E., Lu, B., Gerard, C., Gerard, N.P., 2010, The C5a receptor (C5aR) C5L2 is a modulator of C5aR-mediated signal transduction, Journal Of Biological Chemistry [P], vol 285, issue 10, American Society for Biochemistry and Molecular Biology, Inc., USA, pp. 7633-7644.

Agrawal, L., Maxwell, C.R., Peters, P.J., Clapham, P.R., Liu, S.M., Mackay, C.R., Strayer, D.S., 2009, Complexity in human immunodeficiency virus type 1 (HIV-1) co-receptor usage: roles of CCR3 and CCR5 in HIV-1 infection of monocyte-derived macrophages and brain microglia, Journal Of General Virology [P], vol 90, issue 3, Society for General Microbiology, UK, pp. 710-722.

Gatto, D., Paus, D., Basten, A., Mackay, C.R., Brink, R., 2009, Guidance of B Cells by the Orphan G Protein-Coupled Receptor EBI2 Shapes Humoral Immune Responses, Immunity [P], vol 31, issue 2, Cell Press, USA, pp. 259-269.

Yu, D., Batten, M., Mackay, C.R., King, C., 2009, Lineage specification and heterogeneity of T follicular helper cells, Current Opinion in Immunology [P], vol 21, issue 6, Elsevier Ltd, UK, pp. 619-625.

Maslowski, K.M., Vieira, A.T., Ng, A., Kranich, J., Sierro, F., Yu, D., Schilter, H.C., Rolph, M.S., Mackay-Fisson, F., Artis, D., Xavier, R.J., Teixeira, M.M., Mackay, C.R., 2009, Regulation of inflammatory responses by gut microbiota and chemoattractant receptor GPR43, Nature [P], vol 461, issue 7268, Nature Publishing Group, UK, pp. 1282-1286.

Bluestone, J.A., Mackay, C.R., O'Shea, J.J., Stockinger, B., 2009, The functional plasticity of T cell subsets, Nature Reviews Immunology [P], vol 9, issue 11, Nature Group Publishing, UK, pp. 811-816.

Yu, D., Rao, S., Tsai, L.M., Lee, S.K., He, Y., Sutcliffe, E.L., Srivastava, M., Linterman, M., Zheng, L., Simpson, N., Ellyard, J.I., Parish, I.A., Ma, C.S., Li, Q., Parish, C.R., Mackay, C.R., Vinuesa, C.G., 2009, The transcriptional repressor Bcl-6 directs T follicular helper cell lineage commitment, Immunity [P], vol 31, issue 3, Cell Press, USA, pp. 457-468.

Vogelzang, A., McGuire, H.N., Yu, D., Sprent, J., Mackay, C.R., King, C., 2008, A fundamental role for interleukin-21 in the generation of T follicular helper cells, Immunity [P], vol 29, issue 1, Cell Press, USA, pp. 127-137.

Rittirsch, D., Flierl, M.A., Nadeau, B.A., Day, D.E., Huber-Lang, M., Mackay, C.R., Zetoune, F.S., Gerard, N.P., Cianglone, K., Kohl, J., Gerard, C., Sarma, J.V., Ward, P.A., 2008, Functional roles for C5a receptors in sepsis, Nature Medicine [P], vol 14, issue 5, Nature Publishing Group, USA, pp. 551-557.

Su, Y., Rolph, M.S., Hansbro, N.G., Mackay, C.R., Sewell, W.A., 2008, Granulocyte-macrophage colony-stimulating factor is required for bronchial eosinophilia in a murine model of allergic airway inflammation, Journal Of Immunology [P], vol 180, issue 4, American Association of Immunologists, USA, pp. 2600-2607.

Nossent, J.C., Lester, S., Zahra, D., Mackay, C.R., Rischmueller, M., 2008, Polymorphism in the 5' regulatory region of the B-lymphocyte activating factor gene is associated with the Ro/La autoantibody response and serum BAFF levels in primary Sjogren's syndrome, Rheumatology [P], vol 47, issue 9, Oxford University Press, UK, pp. 1311-1316.

King, C., Tangye, S.G., Mackay, C.R., 2008, T follicular helper (TFH) cells in normal and dysregulated immune responses, Annual Review Of Immunology [P], vol 26, Annual Reviews, USA, pp. 741-766.

Groom, J.R., Fletcher, C.A., Walters, S.N., Gray, S.T., Watt, S.V., Sweet, M.J., Smyth, M.J., Mackay, C.R., Mackay-Fisson, F., 2007, BAFF and MyD88 signals promote a lupuslike disease independent of T cells, Journal of Experimental Medicine [P], vol 204, issue 8, Rockefeller University Press, USA, pp. 1959-1971.

Sierro, F., Biben, C., Martinez-Munoz, L., Mellado, M., Ransohoff, R.M., Li, M., Woehl, B., Leung, H., Groom, J., Batten, M., Harvey, R.P., Matinez-A, C., Mackay, C.R., Mackay-Fisson, F., 2007, Disrupted cardiac development but normal hematopoiesis in mice deficient in the second CXCL12/SDF-1 receptor, CXCR7, Proceedings Of The National Academy Of Sciences O..., vol 104, issue 37, National Academy of Sciences, USA, pp. 14759-14764.

Rolph, M.S., Sisavanh, M., Liu, S.M., Mackay, C.R., 2006, Clues to asthma pathogenesis from microarray expression studies, Pharmacology and Therapeutics [P], vol 109, issue 1-2, Elsevier Inc, USA, pp. 284-294.

Lee, H., Zahra, D., Vogelzang, A., Newton, R., Thatcher, J., Quan, A., So, T., Zwirner, J., Koentgen, F., Padkjaer, S.B., Mackay-Fisson, F., Whitfeld, P.L., Mackay, C.R., 2006, Human C5aR knock-in mice facilitate the production and assessment of anti-inflammatory monoclonal antibodies, Nature Biotechnology [P], vol 24, issue 10, Nature Publishing Group, USA, pp. 1279-1284.

Liu, S.M., Xavier, R., Good, K.L., Chtanova, T., Newton, R., Sisavanh, M., Zimmer, S., Deng, C., Silva, D.G., Frost, M.J., Tangye, S.G., Rolph, M.S., Mackay, C.R., 2006, Immune cell transcriptome datasets reveal novel leukocyte subset-specific genes and genes associated with allergic processes, Journal Of Allergy And Clinical Immunology [P], vol 118, issue 2, Mosby Inc., USA, pp. 496-503.

Jeffrey, K.L., Brummer, T., Rolph, M.S., Liu, S.M., Callejas, N.A., Grumont, R.J., Gillieron, C., Mackay-Fisson, F., Grey, S., Camps, M., Rommel, C., Gerondakis, S.D., Mackay, C.R., 2006, Positive regulation of immune cell function and inflammatory responses by phosphatase PAC-1, Nature Immunology [P], vol 7, issue 3, Nature Publishing Group, USA, pp. 274-283.

Rolph, M.S., Young, T.R., Shum, B.O., Gorgun, C.Z., Schmitz-Peiffer, C., Ramshaw, I.A., Hotamisligil, G.S., Mackay, C.R., 2006, Regulation of dendritic cell function and T cell priming by the fatty acid-binding protein AP2, Journal Of Immunology [P], vol 177, issue 11, American Association of Immunologists, USA, pp. 7794-7801.

Sutherland, A.P., Mackay-Fisson, F., Mackay, C.R., 2006, Targeting BAFF: Immunomodulation for autoimmune diseases and lymphomas, Pharmacology and Therapeutics [P], vol 112, issue 3, Elsevier Inc., United States, pp. 774-786.

Shum, B.O., Mackay, C.R., Gorgun, C.Z., Frost, M.J., Kumar, R.K., Hotamisligil, G.S., Rolph, M.S., 2006, The adipocyte fatty acid-binding protein aP2 is required in allergic airway inflammation, Journal of Clinical Investigation [P], vol 116, issue 8, American Society for Clinical Investigation, USA, pp. 2183-2192.

Wheway, J., Mackay, C.R., Newton, R., Sainsbury, A., Boey, D., Herzog, H., Mackay-Fisson, F., 2005, A fundamental bimodal role for neuropeptide Y1 receptor in the immune system, Journal of Experimental Medicine [P], vol 202, issue 11, Rockefeller University Press, United States, pp. 1527-1538.

Sutherland, A.P., Ng, L., Fletcher, C.A., Shum, B.O., Newton, R., Grey, S., Rolph, M.S., Mackay-Fisson, F., Mackay, C.R., 2005, BAFF augments certain Th1-associated inflammatory responses, Journal Of Immunology [P], vol 174, issue 9, American Association of Immunologists, United States, pp. 5537-5544.

Rodig, S.J., Shahsafaei, A., Li, B., Mackay, C.R., Dorfman, D.M., 2005, BAFF-R, the major B cell-activating factor receptor, is expressed on most mature B cells and B-cell lymphoproliferative disorders, Human Pathology [P], vol 36, issue 10, WB Saunders & Co, USA, pp. 1113-1119.

Ellyard, J.I., Avery, D.T., Mackay, C.R., Tangye, S.G., 2005, Contribution of stromal cells to the migration, function and retention of plasma cells in human spleen: potential roles of CXCL12, IL-6 and CD54, European Journal Of Immunology [P], vol 35, issue 3, Wiley - VCH Verlag GmbH & Co KGaA, Germany, pp. 699-708.

Lutgens, E., Faber, B., Schapira, K., Evelo, C.T., van Haaften, R., Heeneman, S., Cleutjens, K.B., Bijnens, A.P., Beckers, L., Porter, J.G., Mackay, C.R., Rennert, P., Bailly, V., Jarpe, M., Dolinski, B., Koteliansky, V., de Fougerolles, T., Daemen, M.J., 2005, Gene profiling in atherosclerosis reveals a key role for small inducible cytokines: validation using a novel monocyte chemoattractant protein monoclonal antibody, Circulation [P], vol 111, issue 25, Lippincott Williams & Wilkins, USA, pp. 3443-3452.

Chtanova, T., Newton, R., Liu, S.M., Weininger, L., Young, T.R., Silva, D.G., Bertoni, F., Rinaldi, A., Chappaz, S., Sallusto, F., Rolph, M.S., Mackay, C.R., 2005, Identification of T cell-restricted genes, and signatures for different T cell responses, using a comprehensive collection of microarray datasets, Journal Of Immunology [P], vol 175, issue 12, American Association of Immunologists, USA, pp. 7837-7847.

Taberner, M., Scott, K.F., Weininger, L., Mackay, C.R., Rolph, M.S., 2005, Overlapping gene expression profiles in rheumatoid fibroblast-like synoviocytes induced by the proinflammatory cytokines interleukin-1? and tumor necrosis factor, Inflammation Research [P], vol 54, issue 1, Birkhaeuser Verlag AG, Switzerland, pp. 10-16.

Ng, L., Mackay, C.R., Mackay-Fisson, F., 2005, The BAFF/APRIL system: Life beyond B lymphocytes, Molecular Immunology [P], vol 42, issue 7, Pergamon, United Kingdom, pp. 763-772.

Ng, L., Sutherland, A.P., Newton, R., Qian, F., Cachero, T.G., Scott, M.L., Thompson, J.S., Wheway, J., Chtanova, T., Groom, J., Sutton, I.J., Xin, C., Tangye, S.G., Kalled, S.L., Mackay-Fisson, F., Mackay, C.R., 2004, B cell-activating factor belonging to the TNF family (BAFF)-R is the principal BAFF receptor facilitating BAFF costimulation of circulating T and B cells, Journal Of Immunology [P], vol 173, issue 2, American Association of Immunologists, United States, pp. 807-817.

Batten, M., Fletcher, C.A., Ng, L., Groom, J.R., Wheway, J., Laabi, Y., Xin, X., Schneider, P., Tschopp, J., Mackay, C.R., Mackay-Fisson, F., 2004, TNF deficiency fails to protect BAFF transgenic mice against autoimmunity and reveals a predisposition to B cell lymphoma, Journal Of Immunology [P], vol 172, issue 2, American Association of Immunologists, United States, pp. 812-822.

Tsuneyama, K., Harada, K., Yasoshima, M., Hiramatsu, K., Mackay, C.R., Mackay, I.R., Gershwin, M., Nakanuma, Y., 2001, Monocyte chemotactic protein-1, -2, and -3 are distinctively expressed in portal tracts and granulomata in primary biliary cirrhosis: implications for pathogenesis, Journal of Pathology, vol 193, issue 1, John Wiley & Sons Ltd, West Sussux England, pp. 102-109.

Konigs, C., Rowley, M.J., Thompson, P.E., Scealy, M., Davies, J.M., Wu, L., Dietrich, U., Mackay, C.R., Mackay, I.R., 2000, Monoclonal antibody screening of a phage-displayed random peptide library reveals mimotopes of chemokine receptor CCR5: implications for the tertiary structure of the receptor and for an N-terminal binding site fro HIV-1 gp120, European Journal of Immunology, vol 30 issue 4, Wiley-VCH, Germany, pp. 1162-1171.

Postgraduate Research Supervisions

Current Supervision

Program of Study:
(DOCTORATE BY RESEARCH).
Thesis Title:
Diet, microbiota and the asthmatic response.
Supervisors:
Mackay, C (Main), Thorburn, A (Associate).
Program of Study:
(DOCTORATE BY RESEARCH).
Thesis Title:
Role of diet, microbiota and short-chain fatty acids in health and disease.
Supervisors:
Mackay, C (Main), Macia, L (Associate).
Program of Study:
(DOCTORATE BY RESEARCH).
Thesis Title:
The Immunomodulatory Role of Short-chain Fatty Acids.
Supervisors:
Thorburn, A (Main), Mackay, C (Associate).