School of Medicine

Research overview

Determination of the pathophysiological mechanisms underlying renal fibrosis and the progression of chronic kidney disease is a central research theme at the Institute of Nephrology.  Fibrosis is associated with increased cortical synthesis of hyaluronan, a glycosaminoglycan of the extracellular matrix.

My work focuses on the regulation of gene expression in renal disease and current areas of interest include:

·    Transcriptional regulation of the genes encoding the human hyaluronan synthases and other fibrosis-associated genes

·    Post-transcriptional regulation of the human hyaluronan synthase 2 (HAS2) gene by its natural antisense RNA, HAS2AS

·    Post-transcriptional regulation of fibrosis-associated genes by microRNAs

·    The interaction of gene expression and cell phenotype, and the effects of this interaction on the progression of renal disease

Selected key publications

• Identification and analysis of the human hyaluronan synthase 1 gene promoter reveals Smad3- and Sp3-mediated transcriptional induction.
  Chen L, Neville RD, Michael DR, Martin J, Luo DD, Thomas DW, Phillips AO, Bowen T, Matrix Biol, Volume 31, 7-8 (September 2012) pp.373-379
• Analysis of urinary microRNAs in chronic kidney disease.
  Beltrami C, Clayton A, Phillips AO, Fraser DJ, Bowen T, Biochem Soc Trans, Volume 40, 4 (August 2012) pp.875-879
• Transforming growth factor β1 represses proximal tubular cell microRNA-192 expression through decreased hepatocyte nuclear factor DNA binding.
  Jenkins RH, Martin J, Phillips AO, Bowen T, Fraser DJ, Biochem J, Volume 443, 2 (April 2012) pp.407-416
• The human hyaluronan synthase 2 (HAS2) gene and its natural antisense RNA exhibit coordinated expression in the renal proximal tubular epithelial cell.
  Michael DR, Phillips AO, Krupa A, Martin J, Redman JE, Altaher A, Neville RD, Webber J, Kim MY, Bowen T, J Biol Chem, Volume 286, 22 (June 2011) pp.19523-19532
• Sp1 and Sp3 mediate constitutive transcription of the human hyaluronan synthase 2 gene.
  Monslow J, Williams JD, Fraser DJ, Michael DR, Foka P, Kift-Morgan AP, Luo DD, Fielding CA, Craig KJ, Topley N, Jones SA, Ramji DP, Bowen T, J Biol Chem, Volume 281, 26 (June 2006) pp.18043-18050