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Dr Fiona Warner

Baker Heart Research Institute
PO Box 6492, St Kilda Road Central, Melbourne, Vic 8008
Email: Fiona.Warner@baker.edu.au
Tel: +61-3-8532-1182
Fax: +61-3-8532-1100

Our major area of research is concerned with zinc metallopeptidases, cell-surface proteins that are involved in the metabolism of peptide hormones and other bioactive peptides. Zinc metallopeptidases have already provided highly effective therapeutic targets in several diseases. The aim of our group is to extend our knowledge of the structure and function of zinc metallopeptidases that may provide new lead targets for therapeutic development. My current research focuses on the function of angiotensin-converting enzyme 2 (ACE2) a novel homologue of ACE, that has been identified as an essential regulator of heart function, as well as a functional receptor for the SARS coronvirus. Our present aims are to understand the cell biology, post-translational processing and physiological actions of ACE2 in vitro and in vivo. To achieve this, our research group have cloned the ace2 gene for small-scale expression and purification, as well as identified endogenous sources of this peptidase. Using confocal microscopy, western blotting and activity assays, we have shown ACE2 is targeted predominantly to the cell surface where upon the N-terminal ectodomain is cleaved from the cell surface via the action of secretase/s. Both in vitro and in vivo, ACE2 efficiently hydrolyses a number of physiological substrates including angiotensin II, dynorphin A (1-13) and apelin-13. Our future aims are to study the in vivo metabolism of ACE2 and its expression under normal and disease states in relevant tissues.
Professor Tony Turner (University of Leeds, UK)
Professor Nigel Hooper (University of Leeds, U. K.)
Warner, F.J., Smith A.I., Hooper N.M. and Turner A.J. (2004). Angiotensin Converting Enzyme-2: A Molecular and Cellular Perspective. Cell. Mol. Life Sci. (in press).

Guy, J.L., Warner, F.J., Turner A.J. (2002). Large-scale expression and characterisation of an angiotensin-converting enzyme homologue. FASEB J. 16: A1194-A1196.

Warner, F.J., Shang, F., Millard, R.J. and Burcher, E. (2002). Enhancement of neurokinin A-induced smooth muscle contraction in human urinary bladder by mucosal removal and phosphoramidon: relationship to peptidase inhibition. Eur. J. Pharmacol 438: 23-29.

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