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Dr David H Small

Senior Research Fellow

[Colour Photo of Michael]

Telephone:
+61 - 3 9905 1563

Facsimile:
+61 - 3 9905 4699

Email:
David.Small@med.monash.edu.au

Research Interests

David H. Small is an Associate Professorial Fellow and Senior Research Fellow Level B of the National Health and Medical Research Council of Australia and Head of the Laboratory of Molecular Neurobiology. He completed his PhD in biochemistry from the University of Melbourne in 1981 and spent postdoctoral periods at the Massachusetts Institute of Technology in Boston, the Flinders University of South Australia and the University of Melbourne. He is the author of more than 110 publications in international refereed journals and 4 patents. He is on the editorial boards of several journals including Journal of Neurochemistry, Journal of Neuroscience Research, Journal of Alzheimer's Disease and Current Alzheimer's Research and is a member of the International Scientific Advisory Committee for Cholinesterase Conferences, a member of the Review Board of the Medical & Scientific Advisory Council of the Alzheimer's Association (USA) and a member of the International Society for Neurochemistry ISN on the Internet Committee. Dr. Small is a consultant and member of the international scientific advisory board for several pharmaceutical companies including Axonyx Inc. (New York) and Cogstate PLC. and has received more than 20 invitations to speak or chair sessions at international conferences including the Society for Neuroscience (USA), International Brain Research Organisation, European Neuroscience, International Society for Neurochemistry, the Stockholm/Springfield Symposium on Advances in Alzheimer Therapy, and the International Conferences on Alzheimer's disease and related disorders. He has supervised 9 PhD students, 1 MSc. student and 14 Honours students. He is currently Acting Deputy Director of the Monash University Centre for Brain and Behaviour.

Research Links:

Neurobiology

Selected publications (total publication ~120)

  1. Small, D.H. and Carnegie, P.R. (1981) Myelopathy associated with vitamin B12 deficiency - new approaches to an old problem. Trends Neurosci. 4, Nov. X-XI.
  2. Small,D.H. and Wurtman,R.J. (1984) Serotonin binds specifically and saturably to an actin-like protein isolated from rat brain synaptosomes. Proc. Natl. Acad. Sci. USA 81, 959-963.
  3. Small,D.H. (1990) Non-cholinergic actions of acetylcholinesterases: proteases regulating cell growth and development? Trends Biochem. Sci. 15, 213-216.
  4. Small,D.H., Moir,R.D., Fuller,S., Bush,A.I., Li,Q-X, Milward,E., Hilbich,C., Weidemann, A., Beyreuther,K., Masters,C.L. (1991) A protease activity associated with acetylcholinesterase releases the membrane-bound form of the amyloid protein precursor of Alzheimer's disease. Biochemistry 30, 10795-10799.
  5. Small,D.H., Nurcombe,V., Moir,R.D., Michaelson,S., Monard, D., Beyreuther,K., Masters,C.L. (1992) Association and release of the amyloid protein precursor of Alzheimer's disease from chick brain extracellular matrix. J. Neuroscience 12, 4143-4150.
  6. Milward,E.A., Papadopoulos,R., Fuller,S., Moir,R.D., Small,D., Beyreuther,K., Masters,C.L. (1992) The amyloid protein precursor of Alzheimer's disease is a mediator of the effects of nerve growth factor on neurite outgrowth. Neuron 9, 123-127.
  7. Bush, AI, Multhaup, G, Moir, RD, Williamson, TG, Small, DH, Rumble, B., Pollwein, P, Beyreuther, K & Masters, CL. (1993) Identification of a novel zinc(II) binding site on the beta-A4 amyloid protein precursor of Alzheimer's disease. J. Biol. Chem. 268, 16109-16112.
  8. Small, D.H., Nurcombe, V., Clarris, H., Beyreuther, K. & Masters, C.L. (1994) A heparin-binding domain on the amyloid protein precursor of Alzheimer's disease is involved in the regulation of neurite outgrowth. J. Neuroscience 14, 2117-2127.
  9. Small, D.H., Reed, G., Whitefield, B., Nurcombe, V. (1995) Cholinergic regulation of neurite outgrowth from isolated chick sympathetic neurons in culture. J. Neuroscience 15, 144-151.
  10. Li, Q-X., Evin, G., Small, D.H., Multhaup, G., Beyreuther, K. and Masters, C.L. (1995) Proteolytic processing of Alzheimer's disease ßA4 amyloid precursor protein in human platelets. J. Biol. Chem. 270, 14140-14147.
  11. Evin, G., Cappai R., Li, Q.X., Culvenor, J.G., Small, D.H., Beyreuther, K. and Masters, C.L. (1995) Candidate gamma-secretases in the generation of the carboxyl-terminus of the Alzheimer’s disease bA4 amyloid: possible involvement of cathepsin D. Biochemistry 34, 14185-14192.
  12. Brickman, Y., Ford, M., Small, D.H., Bartlett, P.F. and Nurcombe, V. (1995) Heparan sulfates mediate the binding of basic fibroblast growth factor to a specific receptor on neural precursor cells. J.Biol. Chem. 270, 24941-24948.
  13. Williamson, T., Mok, S.S., Henry, A., Cappai, R., Lander, A., Nurcombe, V., Beyreuther, K., Masters, C. and Small, D.H. (1996) Secreted glypican binds to the amyloid protein precursor (APP) of Alzheimer’s disease and inhibits APP-induced neurite outgrowth. J. Biol. Chem. 271, 31215-31221.
  14. Mok, S.S., Evin, G., Li, Q.X., Smith, A.I., Beyreuther, K., Masters, C.L. and Small, D.H. (1997) A novel metalloprotease in rat brain cleaves the amyloid protein precursor of Alzheimer’s disease generating amyloidogenic fragments. Biochemistry 36, 156-163.
  15. Sáez-Valero, J., Sberna, G., McLean, C.A., Masters, C.L. and Small, D.H. (1997) Glycosylation of acetylcholinesterase as diagnostic marker for Alzheimer’s disease. Lancet 350, 929.
  16. Moir, R.D., Lynch, T., Bush, A.I., Whyte, S., Henry, A., Portbury, S., Multhaup, G., Small, D.H., Tanzi, R.E., Beyreuther, K. and Masters, C.L. (1998) Relative increase in Alzheimer’s disease of soluble forms of cerebral Abeta amyloid protein precursor containing Kunitz protease inhibitory forms J. Biol. Chem. 273, 5013-5019.
  17. Sberna G., Sáez-Valero, J., Li, Q.-X., Czech, C., Beyreuther, K., McLean, C., Masters, C.L. and Small, D.H. (1998) Acetylcholinesterase is increased in the brains of transgenic mice expressing the C-terminal fragment (CT100) of the beta-amyloid protein precursor of Alzheimer’s disease. J. Neurochem. 71, 723-731.
  18. Small, D.H. and McLean, C.A. (1999) Alzheimer’s disease and the amyloid beta protein: what is the role of amyloid? J. Neurochem. 73, 443-9.
  19. Small, D.H., Mok, S.S. and Bornstein, J.C. (2001) Alzheimer’s disease and Abeta toxicity: from top to bottom. Nature Reviews Neuroscience 2, 595-598.
  20. Fodero, L.R., McLean, C.A., Robertson, T., Martins, R.N., Beyreuther, K, Masters, C.L., Robertson, T.A. and Small, D.H. (2002) Altered glycosylation of acetylcholinesterase in APP (SW) Tg2576 transgenic mice occurs prior to amyloid plaque deposition. J. Neurochem. 81, 441-448.
  21. Nunan, J and Small, D.H. (2002) Alpha-, beta- and gamma-secretases in the proteolytic processing of the amyloid beta-protein of Alzheimer's disease. in Proteases in Biology and Medicine, Essays Biochem 38 , Portland Press pp. 37-49.
  22. Subasinghe, S., Unabia, S., Barrow, C.J., Mok, S.S., Aguilar, M.I. and Small, D.H. (2003) Cholesterol is necessary both for the toxic effect of Abeta peptides on vascular smooth muscle cells and for Abeta binding to vascular smooth muscle cell membranes. J. Neurochem. 84, 471-479.
  23. Small, D.H. (2004) Do cholinesterase inhibitors boost synaptic scaling in Alzheimer's disease?Trends Neurosci. 27, 245-249.
  24. Hou, X., Richardson, S.J., Aguilar, M.I. and Small, D.H. (2005) Binding of amyloidogenic transthyretin to the plasma membrane alters membrane fluidity and induces neurotoxicity.Biochemistry44, 11618-11627.
  
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