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Dr Siew Yeen Chai
Florey Neuroscience Institutes, Howard Florey Institute
University of Melbourne
Parkville, Victoria 3010
Email: sychai@florey.edu.au
Tel: +61-3-8344-7782
Fax: +61-3-9348-1707
Homepage: http://www.florey.edu.au/about/management-and-staff/scientific-staff/siew-yeen-chai/

Aminopeptidases and carboxypeptidases cleave amino acids from the N- and C-termini of peptide substrates to either generate or degrade biologically active peptides. These enzymes serve important roles and alterations in their activity can impact on a diverse range of physiological processes in both healthy and diseased states. For example, the carboxypeptidase angiotensin converting enzyme (ACE) is involved in the generation of angiotensin II and the degradation of bradykinin, two vasoactive peptides that have opposing roles in the cardiovascular system. The renin-angiotensin system (RAS) plays a critical role in the regulation of blood pressure and fluid balance - drugs that act on this system make up the bulk of the clinically prescribed medication used in the treatment of hypertension and heart disease. My principal research interest is in discovering novel roles for two key enzymes that had been associated with the rennin-angiotensin system, namely angiotensin converting enzyme (ACE) and insulin-regulated aminopeptidase (IRAP) in the brain. My group discovered that peptide inhibitors of IRAP, including angiotensin IV and LVV-hemorphin 7, displayed memory enhancing properties and we propose that IRAP is a therapeutic target useful in the development of a novel class of cognitive enhancers.
Prof Michael Parker, St Vincent’s Institute
Dr Philip Thompson, Department of Medicinal Chemistry, Monash University
Ass Prof Robert Widdop & Dr Tracey Gaspari, Department of Pharmacology, Monash University
Dr Patrick Kehoe, Department of Clinical Science, University of Bristol, UK
Prof Vauquelin Georges, Department of Molecular Biochemistry and Pharmacology, Vrije University, Belgium
Profs Yvette Marchotte and Ilse Smolders, Department of Pharmacology, Vrije University, Belgium
Albiston, A.L., McDowall, S.G., Matsacos, D., Sim, P., Clune, E., Mustafa, T., Lee, J., Mendelsohn, F.A.O., Simpson, R.J., Connolly L.M. and Chai, S.Y. 2001 Evidence that the angiotensin IV (AT4) receptor is the enzyme insulin regulated aminopeptidase. Journal of Biological Chemistry 276(52):48623-48626.

Lee, J.H., Albiston , A.L., Allen, A.M., Mendelsohn, F.A.O., Ping, S.E., Barrett, G.L., Murphy, M., Morris, M.J., McDowall, S.G., and Chai, S.Y. 2004 Effect of intracerebroventricular injection of AT4 ligands, Nle1-Ang IV and LVV-hemorphin-7, on spatial learning. Neuroscience 124:341-349.

Albiston, A.L. Pederson, E.S., Burns, P., Purcell, B., Wright, J.W., Harding, J.W., Mendelsohn, F.A.O., Weisinger, R.S. and Chai S.Y. 2004 Reversal of scopolamine-induced memory deficits by LVV-hemorphin7 in rats in the passive avoidance and Morris water maze paradigms. Behavioral Brain Research 154:239-243.

Peck, G.R., Ye, S., Pham, V., Fernando, R.N., Macaulay, L.S., Chai, S.Y. and Albiston, A.L. 2006 Interaction of the Akt substrate, AS160, with the GLUT4 vesicle marker protein, IRAP. Molecular Endocrinology, 20(10):2576-83.

Jenkins, T.A. and Chai, S.Y. 2007 Effect of chronic angiotensin converting enzyme inhibition on spatial memory and anxiety-like behaviours in rats. Neurobiology of Learning and Memory, 87:218-224.

Albiston, A.L., Peck, G.R., Yeatman, H, Fernando, R., Ye, S. and Chai, S.Y. 2007 Therapeutic targeting of insulin-regulated aminopeptidase: Heads and tails? Pharmacology and Therapeutics 116(3):417-27.

Fernando, R.N., Albiston, A.L. and Chai, S.Y. 2008 The insulin-regulated aminopeptidase IRAP is co-localised with GLUT4 inthe mouse hippocampus - potential role in modulation of glucose uptake in neurons? European Journal of Neuroscience 28:588-598.

Albiston, A.L., Morton, C.J., Ng, H.L., Pham, V., Yeatman, H.R., Ye, S., Fernando, R.N., De Bundel, D., Ascher, D.B., Mendelsohn, F.A.O., Parker, M.W. and Chai, S.Y. 2008 ,Identification and characterization of a new class of cognitive enhancers based on inhibition of insulin-regulated aminopeptidase. FASEB Journal 22(12):4209-4217.

Chai, S.Y., Yeatman, H.R., Parker, M.W., Ascher, D.B., Thompson, P.E., Mulvey, H.T. and Albiston, A.L. 2008 Development of cognitive enhancers based on inhibition of insulin-regulated aminopeptidase. BMC Neuroscience 9(suppl 2):S14.

de Bundel, D., Smolders, I., Yang, R., Albiston, A.L., Michotte, Y. and Chai, S.Y. 2009 Angiotensin IV and LVV-Haemorphin 7 enhance spatial working memory in rats: effects on hippocampal glucose levels and blood flow. Neurobiology of Learning and Memory in press

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