Research Network for Metals in Medicine

 

 

Associate Professor James Camakaris

Position: Head, Department of Genetics, University of Melbourne

Affiliation: University of Melbourne

Postal Address:
Department of Genetics
The University of Melbourne
Parkville, Victoria 3010
AUSTRALIA

Phone: +61 (03) 8344 6246
Fax: +61 (03) 8344 5166
Email: j.camakaris@unimelb.edu.au
Webpage: http://www.genetics.unimelb.edu.au/Camakaris/


Research Profile

James Camakaris has had a consistently high international standing in the area of copper transport, homeostasis and diseases of copper metabolism as judged by a number of criteria (research grants and publications), invited lectures to international conferences(eg 25 since 1993), and invited book chapters(eg 3 since 2002) and reviews. He has published in high impact factor journals (J. Biol. Chem, EMBO J., Human Molecular Genetics, Advances in Protein Chemistry). In 1998 he was appointed Reader and Associate Professor in Genetics and in 1999 was appointed Head of Department,a position which he currently holds. He is coordinator of the final year BSc subject,Human Genetics,and is joint coordinator of stream 1 of the Bachelor of Biomedical Science degree. He has served on NHMRC Regional Grant Interview Committees and on small ARC grants panels. He is currently a Senior Research Associate of the Murdoch Children's Research Institute,a member of the Medical and Scientific committee of the Cancer Council of Victoria and a member of the Synchrotron research grants committee.He is a member of the American Society for Cell Biology,the Human Genetics Society of Australasia,and the Australian Society for Biochemistry and Molecular Biology. In 2000 he was awarded the Australian Institute of Nuclear Science and Engineering (AINSE) Gold Medal for Excellence in research. He has a strong commitment to higher degree education and in 2003 supervised two Honours students and four PhD students in his laboratory and co-supervised four PhD students in off-campus Research Institutes. James Camakaris has extensive experience in studying copper transport and copper resistance mechanisms in cultured mammalian cells, E. coli ,yeast,and Drosophila. He has been associated with a number of discoveries and innovative approaches on investigation of copper homeostasis and resistance mechanisms. He pioneered together with B. Lee, the use of E.coli as a model cell system for studying copper metabolism and this led to cloning of several genes involved in copper homeostasis and resistance. He was one of the first investigators to describe the cellular phenotype of cells from Menkes disease patients and devised the most reliable test for prenatal diagnosis of Menkes disease using amniotic and chorionic villus cells. He isolated copper-resistant mutants of cultured CHO cells which overexpress the Menkes copper transporting P-type ATPase (MNK) and these have been a vital tool in elucidating the regulation and function of the MNK protein. Discovery of the process of copper-induced trafficking of MNK was in his laboratory together with a PhD student under his supervision, M. Petris, who has gone on to make his own major contributions to the field. The paper reporting this discovery (EMBO J 15: 6084-6095, 1996), where James Camakaris was senior author has had a major impact in the field with 206 citations to date. He has developed whole cell and membrane vesicle assays to study copper transport mediated by MNK and developed tools to study the copper-regulated trafficking of the MNK protein. He has published in high ranking journals including the high impact factor journals EMBO Journal, Human Molecular Genetics, Journal of Biological Chemistry and Advances in Protein Chemistry.


Selected Publications

  1. Borchardt, T., Camakaris, J., Cappai, R., Masters, C.L., Beyreuther, K. And Multhaup, G. Copper inhibits amyloid production and stimulates the non-amyloidogenic pathway of amyloid precursor protein (APP) secretion. Biochem. Journal, 344: 461-467 (1999)
  2. Camakaris, J., Voskoboinik, I. and Mercer, J.F. Molecular mechanisms of copper homeostasis. Biochemical and Biophysical Research Communications, 261: 225-232 (1999)
  3. La Fontaine S, Firth, S.D., Lockhart, P.J., Brooks, H., Camakaris, J. and Mercer J.F.B. Functional analysis of the Menkes (MNK) protein expressed from a cDNA construct In Copper transport and its disorders: Molecular and cellular aspects. Kluwer/Plenum Publishing, New York, USA, pp. 67-82 (1999)
  4. La Fontaine S, Firth, S.D., Lockhart, P.J., Brooks, H., Camakaris, J. and Mercer J.F.B. Intracellular localisation and loss of copper responsiveness of MNK, the murine homologue of the Menkes protein, in cells from blotchy (Mo blo) and brindled (Mo br) mouse mutants. Human Molecular Genetics, 8: 1069-1075 (1999)
  5. Petris, M. J., Mercer, J.F.B. and Camakaris, J. The cell biology of the Menkes disease protein. In Copper transport and its disorders: Molecular and cellular aspects. Kluwer/Plenum Publishing, New York, USA, pp. 53-66 (1999)
  6. Voskoboinik, I., Strausak, D., Greenough, M., Brooks, H., Petris, M., Smith, S., Mercer, J.F., and Camakaris, J. Functional analysis of the N-terminal CXXC metal-binding motifs in the human Menkes copper-transporting P-type ATPase expressed in cultured mammalian cells. Journal of Biological Chemistry, 274: 22008-22012 (1999)
  7. White, A.R., Reyes, R., Mercer, J.F.B., Camakaris, J., Zheng, H., Bush, A.I., Beyreuther, K., Masters, C.L. and Cappai, R. Copper levels are increased in the cerebral cortex and liver of APP and APLP2 knockout mice. Brain Research, 842: 439-444 (1999)
  8. White, A.R., Multhaup, G., Maher, F., Bellingham, S., Camakaris, J., Zheng, H., Bush, A.I., Beyreuther, K., Masters, C.L. and Cappai, R. The Alzheimer's Disease Amyloid Precursor Protein Modulates Copper -Induced Toxicity and Oxidative Stress in Primary Neuronal Cultures. The Journal of Neuroscience, 19: 9170-9179 (1999)
  9. Borchardt, T., Schmidt, C., Camakaris, J., Cappai, R., Masters, C.L., Beyreuther, K., Multhaup, G. Differential effects of zinc on amyloid precursor protein (APP) processing in copper-resistant variants of cultured Chinese hamster ovary cells. Cell Mol. Biol. 46: 785-95 (2000)
  10. Voskoboinik, I., Greenough, M., La Fontaine, S., Mercer, J.F.B., and Camakaris, J. Functional studies on the Wilson copper P-type ATPase and Toxic Milk Mouse mutant, Biochem.Biophys. Res. Commun. 281: 966-970 (2001)
  11. Voskoboinik, I, Mar, J., Strausak, D. And Camakaris, J. The regulation of Catalytic activity of the Menkes Copper-translocating P-type ATPase, J. Biol. Chem 276: 28620-28629 (2001)
  12. Burlando, B., Evangelisti, V., Dondero, F., Pons, G., Camakaris, J., and Viarengo, A. Occurrence of a Cu-ATPase in Dictyostelium: possible role in resistance to copper. Biochem. Biophys. Res. Commun. 291: 476-483 (2002)
  13. Lockhart, P.J., Fontaine, S.L. Firth, S.D., Greenough, M., Camakaris, J. and Mercer, J.F.B. Correction of the copper transport defect of Menkes patient fibroblasts by expression of two forms of the sheep Wilson ATPase. Biochemica et Biophysica Acta. 1588: 189-94 (2002)
  14. Mercer, J.F.B., Kramer, D. And Camakaris, J. Molecular basis of diseases of copper homeostasis, Handbook of copper pharmacology and toxicology (E. Massaro Ed.) pp. 249-276. Humana Press NJ. USA (2002)
  15. Petris, M.J., Voskoboinik, I., Cater, M., Smith, K., Kim. B.E., Llanos, R.M., Strausak, D., Camakaris, J. and Mercer, J.F. Copper-regulated trafficking of the Menkes disease copper-ATPase is associated with formation of a phosphorylated catalytic intermediate. J. Biol. Chem. 277: 46736-46742 (2002)
  16. Voskoboinik, I., and Camakaris, J., Menkes copper-translocating P-type ATPase (ATP7A): Biochemical and Cell Biology properties. J. Bioenergetics and Biomembranes 34: 363-371 (2002)
  17. Voskoboinik, I., Camakaris, J., and Mercer, J.F. Understanding the mechanism and function of copper P-type ATPases. Adv. Protein Chemistry Vol. 60 (Valentine, J. and Gralla, E. Eds) pp. 123-150 Elsevier Science, USA (2002)
  18. Voskoboinik, I., Mar, J., and Camakaris, J. Mutational analysis of the Menkes copper P-type ATPase (ATP7A). Biochem. Biophys. Res. Comm. 301: 488-494 (2003)
  19. Voskoboinik, I., Fernando, R., Veldhuis, N., Hannan, K.M., Marmy-Conus, N., Pearson, R.B., and Camakaris, J. Protein kinase-dependent phosphorylation of the Menkes copper P-type ATPase. Biochem. Biophys. Res. Commun. 303: 337-342 (2003)
  20. Lane, C., Petris, M., Benmerah, A., Greenough, M., and Camakaris, J. Studies on endocytic mechanisms of the Menkes copper-translocating P-type ATPase (ATP7A;MNK) Biometals 17: 87-98 (2004)
  21. Pase, L., Voskoboinik, I., Greenough, M., and Camakaris, J. Copper stimulates trafficking of a distinct pool of the Menkes copper ATPase (ATP7A) to the plasma membrane and diverts it into a rapid recycling pool. Biochem. J. (in press; published on Web on Nov. 28, 2003 ahead of print)
  22. Voskoboinik, I., and Camakaris, J. "P-type pumps: Copper pump" In "Encyclopeadia of Biological Chemistry". Elsevier Science (Academic Press) (In press- expected publication date - July 2004. Advised by email on 4/12/03)


Facilities

Fluorescence microscopy, laser scanning confocal microscopy, phosphorimager, inverted fluorescence microscopy, gamma counter and hot room facilities for radioisotope studies inc the strong gamma emitter,copper-64,cell culture facility inc biohazard cabinets.


International Linkages

Professor Nigel Brown (School of Biosciences,University of Birmingham ,UK)
Professor Gerd Multhaup (Berlin University, Germany)
Dr Ludger Johannes (Curie Institute,Paris,France)
Professor Sharon Milgram (University of North Carolina at Chapel Hill,USA)
Dr Michael Petris (Universiy of Missouri,Colubia ,USA)