Professor Michael McGuckin

BSc PhD

Deputy Director (Research)

About me

Mike McGuckin is a NHMRC Principal Research Fellow and is Deputy Director (Research) at at the Mater Research Institute – The University of Queensland within the new Translational Research Institute in Brisbane, where he leads the Mucosal Diseases Research Group.  Mike is the author of over 130 scientific publications with his research currently focused on mucosal infection and chronic inflammation in the gastrointestinal and respiratory tracts, and has held 4 patents. He has particular interests in the role of secreted and cell surface mucin glycoproteins in cancer and in host defense from infection and inflammation. Mike also has a strong interest in the role of protein misfolding and ER stress in secretory cells in chronic inflammatory disease, including diabetes.  He is heavily involved in national and international peer review, is on the Editorial Boards of four international journals, and has served as the lead member of the Academy of the Australian National Health and Medical Research Council for Gastroenterology. Mike chairs the Mater Research Committee, and serves on the Research Committees of the Gastroenterology Society of Australia, University of Queensland Faculty of Medicine and Biomedical Sciences, and chairs the Facilitations Committee of the Translational Research Institute.   In addition he is an elected Councilor for the International Society for Mucosal Immunology, chairs the Medical and Scientific Advisory Committee and serves on the Board of Directors for the Cancer Council Queensland, and is a member of the ANZ Trustees Limited Queensland Medical Research Grant Program Advisory Committee.

Projects

Currently involved in New approach to treating Type 2 Diabetes,  a TRI based research project.

Intersection Between Inflammation and ER Stress

In my laboratory we have discovered that specific inflammatory cytokines are potent inducers of protein misfolding and endoplasmic reticulum stress in secretory cells in multiple tissues.  Additionally, we have discovered that some specific cytokines are potent suppressors of oxidative and ER stress.  ER stress is a common feature of many inflammatory diseases, and in this NHMRC-funded project we are exploring the nexus between inflammation and ER stress in inflammatory disease using murine models and in vitro culture systems.  Aspects of this project involve inflammatory disease in mucosal tissues such as inflammatory bowel diseases and chronic respiratory inflammation, and also inflammation in type 2 diabetes.

Cell Surface Mucins in Gastrointestinal Disease

Cell surface mucins are complex glycoproteins involved in host defence in mucosal tissues such as the gut and lung.  In addition to providing protection from pathogenic microbes these mucins modulate growth, inflammatory signalling and death in mucosal epithelial cells.  In this NHMRC funded project we are exploring how these mucins regulate intracellular signalling in pathways that regulate growth, inflammatory signalling and apoptosis.  In addition, we have found by disabling the anti-apoptotic influence of these proteins that are typically highly expressed in adenocarcinomas, that we can sensitise these cancer to therapy.  We are exploring whether this has potential as an adjunct therapy to traditional treatments for these cancers.

ER stress in inflammatory disease including diabetes; Cell surface mucins in mucosal defence; Therapeutics for Inflammatory Bowel Diseases; Inflammation in human bronchiectasis;

Publications

A selection of recent publications:

  1. Wang R, Hasnain SZ, Tong H, Das I, Chen AC-H, Oancea I, Proctor M, Florin TH, Eri RD, McGuckin MA. (2015) Neutralizing IL-23 is Superior to Blocking IL-17 in Suppressing Intestinal Inflammation in a Spontaneous Murine Colitis Model. Inflammatory Bowel Diseases 21, 973-84.
  2. Hasnain SZ, Borg DJ, Harcourt BE, Tong h, Sheng YH, Ng CP, Das I, Wang R, Chen AC-H, Loudovaris T, Kay TW, Thomas HE, Whitehead JP, Forbes JM, Prins JB, McGuckin MA. (2014)  Glycemic control in diabetes is restored by therapeutic manipulation of cytokines that regulate beta cell stress. Nature Medicine 20, 1417-26.
  3. Benham H, Rehaume L, Hasnain SZ, Velasco J, Baillet A, Ruutu M, Kikly K, Wang Ran, Tseng1 H-W, Thomas G, Brown MA, Strutton G, McGuckin MA, Thomas R. (2014) IL-23-mediates the intestinal response to microbial beta-glucan and the development of spondyloarthritis pathology in SKG mice.  Arthritis & Rheumatology 66, 1755-67.
  4. Serisier DJ, Martin ML, McGuckin MA, Lourie R, Chen A, Brain B, Biga S, Schlebusch S, Dash P, Bowler SD. (2013)  Effect of long-term, low-dose erythromycin on pulmonary exacerbations amongst patients with non-cystic fibrosis bronchiectasis. The BLESS randomized controlled trial.  JAMA 309, 1260-7.
  5. Das I, Png CW, Oancea I, Hasnain SZ, Lourie R, Eri RD, Crane D, Florin TH, McGuckin MA. (2013) Glucocorticoids alleviate ER stress in intestinal secretory cells by enhancing protein folding and degradation of misfolded proteins. Journal of Experimental Medicine 210, 1201-16.
  6. Hasnain SZ, Tauro S, Das I, Tong H, Chen AC-1, Jeffery PL, McDonald V, Florin TH, McGuckin MA. (2013) IL-10 promotes production of intestinal mucus by suppressing protein misfolding and endoplasmic reticulum stress in goblet cells.  Gastroenterology  144, 357-368.
  7. Hasnain SZ, Lourie R, Das I, Chen A, McGuckin MA. (2012) The interplay between endoplasmic reticulum stress and inflammation. Immunology and Cell Biology 90, 260-70.
  8. McGuckin MA, Linden SK, Sutton P, and Florin TH (2011) Mucin Dynamics and Enteric Pathogens. Nature Reviews Microbiology 9, 265-278.
  9. Sheng YH, Lourie R, Linden SK, Jeffery PL, Roche D, Tran T, Png CW, Waterhouse N, Sutton P, Florin TH, McGuckin MA. (2011) The MUC13 Cell Surface Mucin Protects Against Intestinal Inflammation by Inhibiting Epithelial Cell Apoptosis. Gut 60, 1661-1670.
  10. Eri RD, Adams RJ, Tran TV, Tong H, Das I, Roche DK, Oancea I, Png CW, Jeffery PL, Radford-Smith GL, Cook MC, Florin TH, and McGuckin MA. (2011) An intestinal epithelial defect conferring ER stress results in inflammation involving innate and adaptive immunity. Mucosal Immunology 4, 354-64.
  11. McGuckin MA, Eri R, Das I, Lourie R, Florin TH. (2010) ER stress and the unfolded protein response in intestinal inflammation. American Journal of Physiology – Gastrointestinal and Liver Physiology 298, 820-832.
  12. Linden SK, Sheng YH, Every A, Miles KM, Skoog EC, Florin TH, Sutton P, McGuckin MA. (2009) MUC1 limits Helicobacter pylori infection both by steric hindrance and by acting as a releasable decoy.  PLoS Pathogens 5, e1000617.
  13. McGuckin MA, Eri R, Simms LA, Florin TH, Radford-Smith G. (2009) Intestinal barrier dysfunction in inflammatory bowel diseases.  Inflammatory Bowel Diseases 15, 100-113. 
  14. Linden SK, Sutton P, Karlsson NG, Korolik V, McGuckin MA. (2008) Mucins in the mucosal barrier to infection.  Mucosal Immunology 1, 183-197.
  15. Thornton, D.J., Rousseau, K., McGuckin, M.A. (2008) Structure and function of the polymeric mucins in airways mucus.  Annual Review of Physiology 70:5.1–5.28.
  16. Heazlewood CK, Cook MC, Eri R, Price G, Tauro S, Taupin D, Thornton DJ, Png CW, Crockford TL, Cornall, RJ, Adams R, Kato M, Nelms KA, Hong NA, Florin THJ, Goodnow CC, McGuckin MA. (2008) Aberrant mucin assembly in mice causes endoplasmic reticulum stress and spontaneous inflammation resembling ulcerative colitis.  PLoS Medicine 5, e54. 
  17. McGuckin MA, Every A, Skene CD, Linden S, Chionh YT, Swierczak A, McAuley J, Harbour S, Kaparakis M, Ferrero R, Sutton P. (2007) Muc1 mucin limits both Helicobacter pylori colonisation of the murine gastric mucosa and associated gastritis.  Gastroenterology 133, 1210-1218.
  18. McAuley JL, Linden SK, Png CW, King RM, Pennington HL, Gendler SJ, Florin TH, Hill GR, Korolik V, McGuckin MA. (2007) The MUC1 cell surface mucin is a critical element of the mucosal barrier to infection.  Journal of Clinical Investigation 117, 2313-2324.

 

Research fields

inflammatory diseases including inflammatory bowel diseases, respiratory inflammation and diabetes; protein misfolding and ER stress in disease; inflammation and cancer