Cell Biology Research - Institute for Respiratory Health

Cell Biology Research

About

The cell is fundamental to life and any abnormal behaviour may lead to disease. 

The Cell Biology Research Group is investigating how deranged cellular activity contributes to the development of chronic lung diseases such as idiopathic pulmonary fibrosis and chronic obstructive pulmonary disease and whether it is possible to identify suitable therapeutic targets and those patients heading towards decline early enough to intervene.

The group is led by Dr Yuben Moodley, a Respiratory Specialist at Fiona Stanley Hospital and Associate Professor of Respiratory Medicine at the University of Western Australia. The team is a combination of both clinical and laboratory staff and collaborates with peers on a local, national and international level. Their research focus is centred around:

  • Molecular mechanism of chronic inflammation
  • Identifying biomarkers for lung diseases
  • Cell therapies for lung disease
  • Inflammation in Chronic Obstructive Pulmonary Disease (COPD)
  • Immunological and molecular mechanisms underlying chronic airway diseases
  • Host immune defences against bacterial and viral pathogens.

Current research projects

Protective anti-bacterial responses

COPD is a progressive chronic lung condition that causes breathlessness and reduced oxygen levels. There are two main types of COPD – emphysema and chronic bronchitis. Researchers from the Stem Cell Therapy Unit are currently studying the effects of mesenchymal stem cell treatment and the role of exosomes on inflammation and immune cells of COPD patients. The aim of this ongoing study of non-typeable Haemophilus influenza infection in COPD is to characterise anti-bacterial responses of T-cells and monocytes for patients living with COPD.

T-cell co-inhibitory receptors (PD-1, CTLA-4)

COPD is a major cause of morbidity and mortality, especially among smokers and is characterised by chronic irreversible inflammation and progressive decline in lung function. Many COPD patients experience episodes of acute worsening of respiratory symptoms known as exacerbation, which increase the risk of mortality and hospitalisation and are frequently associated with bacterial infections. The causes of these exacerbations are unclear. The Stem Cell Therapy Unit is investigating the causative immune defects so that this disease can be prevented or treated more effectively. It is proposed compromised anti-bacterial immune responses in COPD is due to excess T-cell anti-inflammatory signals, and suppressing these signals may improve the bacterial clearance in these patients. The Unit has previously found that blockade of the inhibitory receptors, CTLA-4 and PD-1 increased bacteria killing and cytokine production by immune cells from the blood. If they demonstrate improvement of bacterial killing by immune cells isolated from COPD patients, this will strongly support the further development of the treatment of COPD.

IPF Biobank

The Stem Cell Therapy Unit continue to manage the National biobank for IPF. Researchers collect, process and store samples from IPF patients for an Australia-wide collection. This biobank aims to enrol all Australians with IPF so that the data collected can help researchers learn more about this serious disorder.

The Unit is also exploring bio-markers for IPF. Using the samples collected in the IPF biobank, they are examining the protein and RNA signatures of the disease progression.

Recent highlights

  • Jesse Armitage, PhD Candidate awarded the prestigious Ann Woolcokc New Investigator Award for 2019.
  • CRE-PF CREATE Fellowship Travel Scholarship and the TSANZ ASM Travel Award awarded to Dr Britt Clynick.

Publications

Past publications

2017

  • Glaspole IN, Watson AL, Allan H, Chapman S, Cooper WA, Corte TJ, Ellis S, Grainge C, Goh N, Hopkins P, Keir G, Macansh S, Mahar A, Moodley Y, Reynolds PN, Ryerson CJ, Walters EH, Zappala CJ, Holland AE. Determinants and outcomes of prolonged anxiety and depression in idiopathic pulmonary fibrosis. Eur Respir J. 2017 Aug 17;50(2).
  • Tan DBA, Armitage J, Teo TH, Ong NE, Shin H, Moodley YP. Elevated levels of circulating exosome in COPD patients are associated with systemic inflammation. Respir Med 2017. doi: 10.1016/j.rmed.2017.04.014.
  • Glaspole IN, Chapman SA, Cooper WA, Ellis SJ, Goh NS, Hopkins PM, Macansh S, Mahar A, Moodley YP, Paul E, Reynolds PN, Walters EH, Zappala CJ, Corte TJ. Health-related quality of life in idiopathic pulmonary fibrosis: Data from the Australian IPF Registry.
  • Respirology. 2017 Jul;22(5):950-956
  • Beers MF, Moodley Y. When Is an Alveolar Type 2 Cell an Alveolar Type 2 Cell? A Conundrum for Lung Stem Cell Biology and Regenerative Medicine. Am J Respir Cell Mol Biol. 2017 Jul;57(1):18-27
  • Jo HE, Glaspole I, Grainge C, Goh N, Hopkins PM, Moodley Y, Reynolds PN, Chapman S, Walters EH, Zappala C, Allan H, Keir GJ, Hayen A, Cooper WA, Mahar AM, Ellis S, Macansh S, Corte TJ. Baseline characteristics of idiopathic pulmonary fibrosis: analysis from the Australian Idiopathic Pulmonary Fibrosis Registry. Eur Respir J. 2017 Feb 23;49(2).
  • Tan DB, Teo TH, Setiawan AM, Ong NE, Zimmermann M, Price P, Kirkham LS, Moodley YP. Increased CTLA-4+ T-cells may contribute to impaired Th1 immune responses in patients with chronic obstructive pulmonary disease (COPD). Immunology 2017. doi: 10.1111/imm.12725.

2016

  • Tjiam MC, Sariputra L, Armitage JD, Taylor JP, Kelleher AD, Tan DB, Lee S, Fernandez S, French MA. Control of early HIV-1 infection associates with plasmacytoid dendritic cell-reactive opsonophagocytic IgG antibodies to HIV-1 p24. AIDS 2016;30:2757-2765.
  • Tan DB, Ong NE, Zimmermann M, Price P, Moodley YP. An evaluation of CD39 as a novel immunoregulatory mechanism invoked by COPD. Hum Immunol 2016;77:916-920.
  • Tan DB, Amran FS, Teo TH, Price P, Moodley YP. Levels of CMV-reactive antibodies correlate with the induction of CD28(null) T cells and systemic inflammation in chronic obstructive pulmonary disease (COPD). Cell Mol Immunol 2016;13:551-553.
  • Moodley Y, Sturm M, Shaw K, Shimbori C, Tan DB, Kolb M, Graham R. Human mesenchymal stem cells attenuate early damage in a ventilated pig model of acute lung injury. Stem Cell Res 2016;17:25-31.
  • Saraswati H, Lee S, Tan D, Yunihastuti E, Gani R, Price P. Increased proportions of dendritic cells and recovery of IFNγ responses in HIV/HCV co-infected patients receiving ART. Hum Immunol 2016;77(1):29-34.
  • Jo HE, Randhawa S, Corte TJ, Moodley Y. Idiopathic Pulmonary Fibrosis and the Elderly: Diagnosis and Management Considerations.
  • Drugs Aging. 2016 May;33(5):321-34
  • Chung LP, Lake F, Hyde E, McCamley C, Phuangmalai N, Lim M, Waterer G, Summers Q, Moodley Y. Integrated multidisciplinary community service for chronic obstructive pulmonary disease reduces hospitalisations. Intern Med J. 2016 Apr;46(4):427-34.
  • Jo HE, Corte TJ, Moodley Y, Levin K, Westall G, Hopkins P, Chambers D, Glaspole I. Evaluating the interstitial lung disease multidisciplinary meeting: a survey of expert centres. BMC Pulm Med. 2016 Feb 1;16:22.

2015

  • Tjiam MC, Taylor JP, Morshidi MA, Sariputra L, Burrows S, Martin JN, Deeks SG, Tan DB, Lee S, Fernandez S, French MA. Viremic HIV Controllers Exhibit High Plasmacytoid Dendritic Cell-Reactive Opsonophagocytic IgG Antibody Responses against HIV-1 p24 Associated with Greater Antibody Isotype Diversification. J Immunol 2015;194:5320-5328.
  • Moodley Y, Corte T, Richeldi L, King TE Jr. Do all patients with idiopathic pulmonary fibrosis warrant a trial of therapeutic intervention? A pro-con perspective. Respirology. 2015 Apr;20(3):389-94.

2014

  • Tan DBA, Fernandez S, Price P, French MA, Thompson PJ, Moodley YP. Impaired function of regulatory T-cells in patients with chronic obstructive pulmonary disease (COPD). Immunobiology 2014;219:975-979.
  • Kim K, Perera R, Tan DB, Fernandez S, Seddiki N, Waring J, and French MA. Circulating mycobacterial-reactive CD4+ T cells with an immunosuppressive phenotype are higher in active tuberculosis than latent tuberculosis infection. Tuberculosis 2014; 94:494-501.
  • Tan DB, Fernandez S, Price P, French MA, Thompson PJ, Moodley YP. Impaired CTLA-4 responses in COPD are associated with systemic inflammation. Cell Mol Immunol 2014;11:606-608.
  • Moodley Y, Goh N, Glaspole I, Macansh S, Walters EH, Chapman S, Hopkins P, Reynolds PN, Zappala C, Cooper W, Mahar A, Ellis S, McCormack S, Darbishire W, Wood-Baker R, Corte TJ; Australian IPF Registry Steering Committee. Australian Idiopathic Pulmonary Fibrosis Registry: vital lessons from a national prospective collaborative project. Respirology. 2014 Oct;19(7):1088-91.
  • Troy L, Glaspole I, Goh N, Zappala C, Hopkins P, Wilsher M, Moodley Y, Corte T. Prevalence and prognosis of unclassifiable interstitial lung disease. Eur Respir J. 2014 May;43(5):1529-30.
  • Kim K, Waterer G, Thomson R, Yang IA, Nashi N, Tan DB, Price P. Levels of anti-cytokine antibodies may be elevated in patients with pulmonary disease associated with non-tuberculous mycobacteria. Cytokine 2014;66(2):160-163.
  • Tan DB, Fernandez S, Price P, Moodley YP. The proportion and function of peripheral myeloid-derived suppressor cells do not correlate with systemic inflammation in chronic obstructive pulmonary disease. Hum Immunol 2014;75(1):5-9.
  • Ding, H., Karunanithi, M., Kanagasingam, Y., Vignarajan, J., Moodley, Y.P. 2014. A pilot study of a mobile-phone-based home monitoring system to assist in remote interventions in cases of acute exacerbation of COPD. Journal of Telemedicine and Telecare, 20, 3, pp. 128-134.
  • Tan, D., Fernández, S.H., Price, P.J.S., Moodley, Y.P. The proportion and function of peripheral myeloid-derived suppressor cells do not correlate with systemic inflammation in chronic obstructive pulmonary disease. Human Immunology, 2014, 75, 1, pp. 5-9.
  • Tan, D., Fernández, S.H., Price, P.J.S., French, M.A.H., Thompson, P.J., Moodley, Y.P. Impaired CTLA-4 responses in COPD are associated with systemic inflammation. Cellular and Molecular Immunology 2014, 11, 6, pp. 606-608.
  • Tan, D., Fernández, S.H., Price, P.J.S., French, M.A.H., Thompson, P.J., Moodley, Y.P. Impaired function of regulatory T-cells in patients with chronic obstructive pulmonary disease (COPD). Immunobiology 2014, 219, 12, pp. 975-979.

Prior to 2014

  • Moodley Y, Vaghjiani V, Chan J, Baltic S, Ryan M, Tchongue J, Samuel CS, Murthi P, Parolini O, Manuelpillai U. Anti-inflammatory effects of adult stem cells in sustained lung injury: a comparative study. PLoS One 2013;8(8):e69299.
  • Kolios, G., Moodley, Y.P. Introduction to stem cells and regenerative medicine. RESPIRATION, 2013, 85, pp. 3-10.
  • Moodley, Y., Vaghjiani, V., Chan, J., Baltic, S., Ryan, M., Tchongue, J., Samuel, C.S., Murthi, P., Parolini, O., Manuelpillai, U. Anti-Inflammatory Effects of Adult Stem Cells in Sustained Lung Injury: A Comparative Study. PLoS ONE, 8, 8, pp. e69299 2013.
  • Tan DBA, Price P. Reply to ‘TLR-2 ligand lipomannan from Mycobacterium tuberculosis does not stimulate inflammatory cytokines in dendritic cells’. AIDS 2012;26:184-1185
  • Tan DB, Lim A, Yong YK, Ponnampalavanar S, Omar S, Kamarulzaman A, French MA, Price P. TLR2-induced cytokine responses may characterize HIV-infected patiens experiencing mycobacterial immune restoration disease. AIDS 2011;25:1455-1460.
  • Tan DB, Yong YK, Lim A, Tan HY, Kamarulzaman A, French M, Price P. Robust IFNα and IL-12 responses by dendritic cells are related to efficient CD4+ T-cell recovery in HIV patients on ART. Clin Immunol 2011;139:115-121.
Our People
The Stem Cell Therapy Unit is made up of a multi-disciplinary team of doctors, scientists and students.