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Dr Paul Coughlin
Australian Centre for Blood Diseases, Monash Department of Medicine
Monash University
Level 5, Clive Ward Centre, Arnold Street, Box Hill, 3128
Email: Paul.Coughlin@med.monash.edu.au
Tel: +61-3-9895 0365
Fax: +61-3-9895 0332

Our group is currently focussed on the biology of the A clade serpins. In particular we are interested in the evolutionary relationship between human antitrypsin and antichymotrypsin and their murine equivalents represented by expanded clusters of 5 and 14 genes respectively. We have examined the patterns of expression of the murine genes and are moving on to study the factors driving tissue specific transcription. At a biochemical and biophysical level we are systematically studying the properties of recombinant members of the murine antichymotrypsin-like serpins.
The human A clade serpin cluster on chromosome 14q32 contains 12 genes. Of these, 9 have been well studied. There are however 3 genes (serpins A9, A11 and A12) which are enigmatic. SerpinA9 (centerin) is produced by germinal centre B cells and its expression is increased in B cell lymphomas but nothing is known of its biochemical or cell biology properties. We are examining serpinA9 recombinant protein and exploring its role in the normal and malignant B cell function. We are also developing work on serpinA11 which is expressed in fetal liver, and serpinA12 which is expressed by malignant melanomas.
Robert Pike, Steve Bottomley and Jamie Rossjohn, Department of Biochemistry and Molecular Biology, Monash University.

Ivan Bertoncello and Jean-Pierre Levesque, Peter MacCallum Cancer Insitute.
Silverman, G.A., Bird, P.I., Carrell, R.W., Coughlin, P.B., Gettins, P.G., Irving, J.I., Lomas, D.A., Luke, C.J., Moyer, R.W., Pemberton, P.A., Remold-ODonnell, E., Salvesen, G.S., Travis, J.& Whisstock, J.C. (2001) The serpins are an expanding superfamily of structurally similar but functionally diverse proteins: Evolution, mechanism of inhibition, novel functions, and a revised nomenclature. Journal of Biological Chemistry. 2001;276(36):33293-6.

Morris EC, Dafforn TR, Forsyth SL, Missen MA, Horvath AJ, Hampson L, Hampson IN, Currie G, Carrell RW, Coughlin PB. Murine serpin 2A is a redox sensitive intracellular protein. Biochem J 2003; 371(1):165-73.

Sharon Forsyth, Anita Horvath and Paul Coughlin. The murine a1-antitrypsin and a1-antichymotrypsin multi-gene clusters: a review and comparison with the human clade A serpins. Genomics 2003; 81(3):336-45.

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