The effect of hypoxia-inducible factor 2 activation on macrophage function in Idiopathic Pulmonary Fibrosis. (360G-Wellcome-110086_Z_15_Z)
Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease causing hypoxemia and fatal respiratory failure. Incomplete understanding of pathogenic mechanisms hinders the development of effective therapies. Sudden deterioration due to acute exacerbations (AE-IPF), often triggered by infection, lead to rapid deterioration in the patients condition, often proving fatal. Lung macrophages are long-lived, highly oxygen sensitive, cells implicated in IPF pathogenesis. Their phenoty pe dictates their function. In IPF, alveolar macrophages (AM) are predominantly alternatively-activated (AAM). As IPF progresses, hypoxia activates hypoxia-inducible factors (HIF), with HIF-2, rather than HIF-1, found mainly in AAM. HIF-2 deletion in neutrophils improves infection resolution, however the role of HIF-2 in macrophage function and bactericidal activity, particularly in IPF, remains unknown. I aim to determine the role of HIF-2 in macrophages in IPF using mouse models of fibrosis, as well as human macrophages from IPF sufferers. I will also investigate the effects of HIF-2 activation in macrophages on their metabolic function and their phenotype. In order to assess the role of macrophages in AE-IPF, I will investigate the phenotype plasticity, as well as the bactericidal capacity of AM from mice undergoing lung fibrosis models, as well as from human IPF patient samples.
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Grant Details
Amount Awarded | 325999 |
Applicant Surname | Mirchandani |
Approval Committee | Clinical Interview Committee |
Award Date | 2015-11-19T00:00:00+00:00 |
Financial Year | 2015/16 |
Grant Programme: Title | Postdoctoral Training Fellowship for Clinicians |
Internal ID | 110086/Z/15/Z |
Lead Applicant | Dr Ananda Mirchandani |
Partnership Value | 325999 |
Planned Dates: End Date | 2021-01-31T00:00:00+00:00 |
Planned Dates: Start Date | 2016-03-01T00:00:00+00:00 |
Recipient Org: Country | United Kingdom |
Region | Scotland |
Sponsor(s) | Prof Moira Whyte, Prof Sarah Walmsley |