Dr Siew Yeen Chai

Dr Siew Yeen Chai
Dr Siew Yeen Chai

BSc (Hons) (Mon) PhD (Melb)

Senior Research Fellow
Neuropeptides Group
Laboratory Head, Neurochemistry Laboratory

Contact Details

Email:

siew.yeen.chai@florey.edu.au

Phone:

+61 (0)3 8344 7782

Fax:

+61 (0)3 9348 1707

Research Interests

Aminopeptidases and carboxypeptidases cleave amino acids from the N- and C-termini of peptide substrates to either generate or degrade biologically active peptides. Therefore, these enzymes serve important roles in physiology and alterations in their activity can impact on a diverse range of physiological processes in both healthy and diseased states. One example of such an enzyme is the carboxypeptidase, angiotensin-converting enzyme (ACE), which is involved in the generation of angiotensin II and the degradation of bradykinin, two vasoactive peptides that have opposing roles in the cardiovascular system. Inhibitors of this enzyme are used widely and very effectively to treat hypertension and congestive heart failure. Patients on ACE inhibitors appear to feel better and perform better in cognitive tasks suggesting that these drugs have central nervous system action.

My research team has previously demonstrated that ACE inhibitors can access sites within the brain to inhibit brain ACE, thereby altering the levels of some neurotransmitters. We are currently conducting a comprehensive and systematic investigation in animals of the effects of ACE inhibitor treatment on mood, stress levels and cognitive function. Results from our experiments will provide insights into the role of ACE in the brain and further our understanding of the effects of ACE inhibitor treatment in humans.

The other enzyme that is part of my research focus is insulin-regulated aminopeptidase, IRAP, which was originally identified in adipose tissue and skeletal muscles as a marker protein for specialised vesicles that contains the insulin-responsive glucose transporter GLUT4. My research group discovered that IRAP exists in high levels in the brain. We also found that central administration of peptide inhibitors of IRAP result in enhanced performance in learning and memory tasks in normal animals and more importantly reversal of different forms of memory deficits. We propose that IRAP is a novel target that can be used to develop a new class of cognitive enhancing agent. We are currently investigating the roles of IRAP in the brain and developing a new class of neurotherapeutics targeting this enzyme.

Publications and Articles

Please see PubMed.

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.

Albiston, A.L., Mustafa, T., McDowall, S.G., Mendelsohn, F.A.O., Lee J.H. and Chai, S.Y. 2003 The angiotensin IV receptor is insulin regulated membrane aminopeptidase: potential mechanisms of memory enhancement.  Trends in Endocrinology and Metabolism, 14(2):72-77.

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.

Chai, S.Y., Fernando, R., Ye S., Peck, G. and Albiston, A.L. 2004 Insulin-regulated Aminopeptidase  In : Aminopeptidases In Biology and Disease  Editors  Hooper N. and  Lendeckel U., Kluwer-Plenum Publishers p 61-82.

Fernando, R., Larm, J., Albiston, A.L. and Chai, S.Y.  2005 Distribution and cellular localization of the insulin regulated aminopeptidase (IRAP) in the rat central nervous system.  Journal of Comparative Neurology, 487:372-390.

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.

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