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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
Homepage:
Research |
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.
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Collaborations |
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.
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Publications |
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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