Supervisor View Full Details

Supervisor View 2
October 3, 2016
Supervisor View Full Details 2nd
October 12, 2016

Prof Michael P Keane

Organisation:University College Dublin

Webpage:www.ucd.ie

Email AddressEmail hidden; Javascript is required.

Research Fields
  • genetics, genomics and molecular biology
  • cell and developmental biology/regenerative medicine
Postgrad Medical Specialites
  • Medicine
  • Pathology
Medical Subspecialties
  • Immunology
  • Radiology
  • Respiratory Medicine
  • Rheumatology
My Work

Research interests include the biology of idiopathic pulmonary fibrosis including the mechanisms and mediators involved in the pathogenesis of the disease. Current research studies include the function and regulation of the IL-13 receptors, regulation of fibrocytes differentiation and the potential of mesenchymal cells to attenuate fibrosis. We also have ongoing studies of the role of exosomes in the biology of fibrosis and lung cancer.

Potential Projects

The contribution of miR-125b and miR-7, from serum exosomes of IPF patients, to the progression of fibrosis in IPF.
Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal disease. Exosomes are extracellular microvesicles that are involved in cell-cell signalling due to their ability to transport DNA, proteins and RNA molecules between cells; thereby allowing cells to exert biological functions at distant sites. MicroRNA isolated from exosomes has been implicated in several fibrotic models.

We have previously found upregulation of two fibrotic micro RNAs in the serum exosomes of IPF patients compated to healty controls; miR-125b and miR7. MicroRNA 125b expression correlated well with disease burden as defined by GAP index, and the degree of up regulation of miR-7 correlates significantly with honeycombing and percentage reticulation. We also found that CD63 the exosomal marker was differentially glycosylated in IPF exosomes as compared to healthy control exosomes. This may play a role in exosome function in IPF.

This new project will aim to further this preliminary data. This data identifies two potentially novel micro RNA biomarkers that may provide insights into pathogenesis of the disease, which we will investigate. Inhibiting up regulated miRNA or supplementing down regulated miRNA may be potential therapeutic targets.

The differential glycosylation of the exosomal enriched protein CD63 warrants further investigation. Glycosylation of these proteins may play a role in the docking of exosomes at its target site. We would like to further investigate this as inhibition of docking would prevent transfer of information and could provide a target for intervention in diminishing the fibrotic response to injury in the lung.

Together these objectives will add to the limited knowledge of the role of exosomes in lung disease, and may hold the key to the fibrotic process that is detrimental to the function of the lung in IPF.