Mucosal Diseases

Stress-inducing pathways are inappropriately activated in non-infectious inflammatory diseases, exacerbating tissue damage and perpetuating a cycle of stress and inflammation

 

On-going Projects

  • Cellular Stress in Intestinal Epithelial Cells

    Discovery: Specific cytokines, fats and environmental factors can induce Unfolded Protein Response in secretory cells, like goblet cells in the intestine. Our aim is to modulate oxidative and ER stress by neutralising or replenishing specific cytokines, to assess whether this reduces epithelial cell death and inflammatory signalling, and aids restoration of mucosal barrier in acute and chronic models of mucosal inflammation.

  • Therapeutic Potential of IL-20 family cytokines in IBD

    Discovery: Several forms of Interleukin-22 is in clinical trials for Inflammatory Bowel Disease (IBD). IL-22 and its family members play an important role in maintaining gut barrier integrity. We are investigating the role of endogenous role of these cytokines in IBD and assessing whether modulation of these cytokines can improve pathology in disease.

  • Understanding the drivers of Mucosal Pathology

    Discovery: There is increasing evidence for an important role of ER stress in the development of mucosal inflammation in context of spondyloarthropathies, obesity driven changes in the intestine, ulcerative colitis, Non-Cystic Fibrosis Bronchiectasis and Asthma. By combining multi-disciplinary approaches, we aim to dissect the role of cytokines and ER stress factors in driving immunopathology.

Publications

Mucus and Mucins: The Underappreciated Host Defence System

Sheng YH, Hasnain SZ. Front Cell Infect Microbiol. 2022 Jun 14;12:856962.

Pre-Diabetes Increases Tuberculosis Disease Severity, While High Body Fat Without Impaired Glucose Tolerance Is Protective.

Sinha R, Ngo MD, Bartlett S, Bielefeldt-Ohmann H, Keshvari S, Hasnain SZ, Donovan ML, Kling JC, Blumenthal A, Chen C, Short KR, Ronacher K. Front. Cell Infect Microbiol. Jul 2021.

DP1 prostanoid receptor activation increases the severity of an acute lower respiratory viral infection in mice via TNF-α-induced immunopathology.

Ullah MA, Rittchen S, Li J, Hasnain SZ, Phipps S. Mucosal Immunol. 2021 Jul;14(4):963-972. Epub 2021 Apr 20.

Immune-driven alterations in mucin sulphation is an important mediator of Trichuris muris helminth expulsion.

Hasnain SZ, Dawson PA, Lourie R, Hutson P, Tong H, Grencis RK, McGuckin MA, Thornton DJ. PLoS Pathog. (2017) 13;13(2):e1006218.

Mucin  gene  deficiency  in  mice  impairs host resistance to an enteric parasitic infection.

Hasnain  SZ, Wang  H, Ghia JE, Haq  N, Deng  Y, Velcich  A, Grencis  RK, Thornton  DJ and  Khan  W I.   Gastroenterology.  (2010) 138(5):763-71.

Influence of the MUC1 Cell Surface Mucin on Gastric Mucosal Gene Expression Profiles in Response to Helicobacter pylori Infection in Mice.

Sheng YH, Ng GZ, Summers KM, Every AL, Price G, Hasnain SZ, Sutton P, McGuckin MA. Front Cell Infect Microbiol. 2020 Jul 24;10:343. doi: 10.3389/fcimb.2020.00343

High glucose levels increase influenza-associated damage to the pulmonary epithelial-endothelial barrier.

Hulme KD, Yan L, Marshall RJ, Bloxham CJ, Upton KR, Hasnain SZ, Bielefeldt-Ohmann H, Loh Z, Ronacher K, Chew KY, Gallo LA, Short KR. eLife (2020); 9:e56907.DOI: 10.7554/eLife.56907

Serine Protease(s) secreted by the nematode Trichuris muris degrade the mucus barrier. 

Hasnain SZ, McGuckin	MA, Grencis RK	and Thornton DJ. PLoS Neglected Tropical Diseases. (2012) 6(10):e1856

Changes in the mucosal barrier during acute and chronic Trichuris muris infection.

Hasnain SZ, Thornton DJ and Grencis RK. Parasite Immunology. (2011) 33(1): 44-45.

PPARγ is reduced in the airways of non-CF bronchiectasis subjects and is inversely correlated with the presence of Pseudomonas aeruginosa.

Burr LD, Rogers GB, Chen AC, Taylor SL, Bowler SD, Keating RL, Martin ML, Hasnain SZ, McGuckin MA. PLoS One. 2018 Aug 16;13(8):e0202296. doi:10.1371/journal.pone.0202296.

Immune regulation of the unfolded protein response at the mucosal barrier in viral infection.

Wang R, Moniruzzaman M, Shuffle E, Lourie R,  Hasnain SZ. Clin Transl Immunology. 2018. 3;7(4):e1014. doi:10.1002/cti2.1014. eCollection 2018. Review.

Muc5ac: a critical  component mediating   the   rejection    of   the   enteric  nematodes.

Hasnain SZ, Evans  C,  Roy  M,  Gallagher  AL, Kindrachuk  KN,  Barron  L, Dickey  BF, Wilson MS, Wynn TA, Grencis RK and Thornton DJ. Journal  of  Experimental Medicine. (2011) 208 (5): 893.

A new role for mucins in immunity: insights from gastrointestinal nematode infection.

Hasnain SZ, Gallagher A, Grencis RK and Thornton DJ. The International Journal of Biochemistry & Cell Biology. (2012). S1357-2725(12)00357-3.