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Dr Cathy Abbott
School of Biological Sciences
Flinders University
GPO Box 2100, Adelaide, SA 5001
Email: Cathy.Abbott@flinders.edu.au
Tel: +61-8-8201 2078
Fax: +61-8-8201 3015
Homepage:

Research
Hormones and neuropeptides regulate normal processes such as digestion, hunger, eating behaviour and defence. These signalling molecules are also involved in tumour formation and progression and in controlling tissue damage and repair that occur during wounding to the skin or during liver disease. The biological activity of these peptides is often guarded by molecular scissors called proteases. In our work we are interested in two different type of molecular scissors the dipeptidyl peptidases and metalloproteases.
The dipeptidyl peptidase (DP) IV gene family of atypical serine proteases have been implicated in T cell proliferation, chemokine biology, type II diabetes, HIV infection and tumour growth. Other members of this family include the enzymes fibroblast activation protein, DP8 and DP9 and two related genes which lack peptidase activity DPL1 and DPL2. Work in this group focuses on understanding more about the natural substrates and ligands of these molecules and the role this family plays in inflammatory bowel disease, wound repair and cancer progression. .
Betacellulin (BTC) belongs to the EGF family of growth factors. EGF family factors are expressed as transmembrane precursors that undergo proteolytic ectodomain shedding to release a soluble mature growth factor. Ectodomain shedding of EGF-family factors is a critical step in tumour progression. We are working on the role and nature of the metalloproteases and chemical activators that regulate the BTC shedding process.
In the future this research could help uncover novel roles for these proteases in disease progression and could ultimately lead to the development of protease inhibitors for use as novel therapeutics.
Collaborations
Dr Mark Gorrell, Royal Prince Alfred Hospital (RPA), Sydney, Australia.
Professor Geoffrey McCaughan, AW Morrow Gastroenterology and Liver Centre, RPA, Sydney, Australia
Dr Gordon Howarth, Child Health Research Institute, Adelaide, Australia
Prof Dr Ingrid De Meester, Department of Pharmaceutical Sciences University of Antwerp Belgium
Dr Andy Dunbar, GROPEP, Adelaide, Australia.
Dr Peter Dempsey,Pacific Northwest Research Institute, Seattle, USA.
Publications
Abbott CA, McCaughan GW and Gorrell MD. Two highly conserved glutamic acid residues in the predicted b propeller domain of dipeptidyl peptidase IV are required for its enzyme activity. FEBS Letters 458:3, 278-284 (1999)

Abbott CA, Levy MT, McCaughan GW, Church B and Gorrell MD. Adenosine deaminase and antibodies that inhibit binding by this ligand have distinct, discontinuous binding sites on the beta-propeller domain of human CD26. European Journal of Biochemistry 266: 3, 798-810 (1999)

Abbott CA, Yu D, Woollatt E, Sutherland GR, McCaughan GW and Mark D Gorrell. Cloning, expression and chromosomal localization of a novel human dipeptidyl peptidase (DPP)IV homologue, DPP8. European Journal of Biochemistry 267:6140-6150(2000)

Abbott CA and Gorrell MD. The Family of CD26/DPIV and Related Ectopeptidases - The DPIV Family in Ectopeptidases: CD13/aminopeptidases N and CD26/Dipeptidyl peptidase IV in medicine and Biology, Kluwer Academic New York, 171-195(2002)

Ajami K, Abbott CA, Obradovic M, Gysbers V, Kahne T, McCaughan GW and Gorrell MD. Structural requirements for catalysis, expression and dimerisation in the CD26/DPPIV gene family, Biochemistry USA, Jan 28;42(3):694-701 (2003)





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