School of Paediatrics and Child Health

Leesa Harris


 Leesa Harris

Contact

Leesa Harris

School of Paediatrics & Child Health
M561
The University of Western Australia
Princess Margaret Hospital for Children
PO Box D 184, Subiaco
WA 6840

Phone (+61) 9340 8625
Fax (+61) 9388 2097

Supervisors

Start Date

January 2014

Submission Date

January 2018


Leesa Harris

Thesis

Contribution of microarray identified genes and pathways to wheezing attacks and treatment response.

Summary

Asthma is a chronic respiratory disease affecting 1 in 10 Australians. It is caused by interactions between genetic and environmental factors.  Asthma attacks are the worst form of this disease, characterised by a lack of control over asthma symptoms such as, wheezing, cough, shortness of breath and chest tightness, where additional treatment is required. Asthma attacks are a leading cause of hospitalisation in Australian children and while treatments exist, they are not always effective in all patients.

Asthma attacks can be triggered by infections with respiratory viruses such as human rhinovirus (HRV). Studies in Perth, Hong Kong and South Africa have shown that HRV infects over 80% of children having an asthma attack who are infected with a respiratory virus. HRV is classified into three species: A, B and C. HRV-A and HRV-C are the most common viruses infecting children during an asthma attack as well as other wheezing illnesses (virus-induced wheeze and bronchiolitis). HRV-C is associated with greater attack severity and a higher number of lung-related hospital admissions in children. HRV also increases the amount of certain immune system components such as interferon-γ-induced protein (IP)-10 and interleukin (IL)-6, in immune cells from asthmatic adults compared to non-asthmatics.

We have compared the gene expression levels in circulating immune cells (peripheral blood mononuclear cells (PBMC)) between: (1) acute asthmatic children compared to when they have recovered and (2) children with acute wheezing illnesses compared to controls, using two independent microarrays. Of the 29 genes up-regulated in both microarrays, we have selected five steroid responsive candidates which had variations in their DNA sequence associated with expression levels, acute asthma susceptibility, severity, and treatment response in preliminary analysis.

The aim of my thesis is to investigate the contribution of sequence variations in these five candidate genes with encoded expression levels and clinical measures of HRV-induced wheezing illness severity in children. Gene variations studied will consist of both known and novel (that I will identify in exome sequencing data). I will also investigate gene expression, IP-10 and IL-6 production in PBMC cells, exposed to HRV-A, HRV-C and corticosteroid treatment, collected from children with a wheezing attack and controls.

Why my research is important

Sequence variations in these five candidate genes haven’t been well investigated in wheezing illnesses, including asthma attacks.  The outcomes of this study will potentially provide knowledge that will assist in identifying children at a high risk of persistent asthma after their first presentation, develop targets for treatments to inhibit pathways associated with HRV-induced wheeze and/or develop preventative measures for children with higher rates of hospitalisation.

Funding

  • Australian Postgraduate Award
  • UWA Top Up Award

 

 

 

 

 


 

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Last updated:
Monday, 1 September, 2014 3:08 PM

http://www.paediatrics.uwa.edu.au/2589341