Research

The major focus of our laboratory is to unravel the molecular and cellular underpinnings of metal homeostasis in mammals.

Transition metals are essential cofactors that function in specific biochemical pathways including respiration, neuropeptide production, signal transduction, connective tissue and pigment synthesis, detoxification, and nucleic acid regulation. Although largely underexplored, new evidence now implicates transition metals in broad biological processes such as aging, neoplasia and embryogenesis as well as in the etiology of many neurological diseases. Metals have to be acquired exogenously by organisms and can be limiting. In humans, perinatal malnutrition of these micronutrients may influence intelligence and learning two generations subsequent to birth. Redox-active metals in excess, however, are toxic to cells because of their ability to generate reactive oxygen and hydroxyl radicals. Thus, in organisms specific intracellular pathways exist for efficient acquisition, sequestration and delivery of metals. The long-term objective of my research is to explore the role of these cofactors in biological processes. One interest of the lab are the mechanisms that govern intracellular copper trafficking by the metallochaperone Atox1 and discerning its physiological function in mammals utilizing knock-out mice and primary cell cultures. In addition, we intend to use a molecular-genetic approach first with genetically tractable model organisms such as the nematode Caenorhabditis elegans and yeast Saccharomyces cerevisiae to rapidly screen for mutants and identify the corresponding genes that show aberrant metal metabolism and then use this molecular blueprint to pinpoint orthologous genes in mammals. Our studies are focused on elucidating the molecular and cellular mechanisms of metal ion homeostasis and utilizing this knowledge to develop novel nutritional approaches to human health and disease.

Visit my homepage for more details http://ansc.umd.edu/I_Hamza/Hamza%20Webpage_2.htm

Selected Publications

Hamza I, Schaefer M, Klomp LWJ and Gitlin JD. Interaction of the copper chaperone HAH1 with the Wilson disease protein is essential for copper homeostasis. Proc. Natl. Acad. Sci. 1999; 96:13363-13368.
Hamza I and Gitlin JD. Copper metabolism and the Liver. In: The Liver: Biology and Pathobiology. I Arias, Boyer, F Chisari, N Fausto, D Schachter and D Shafritz (eds) Williams and Wilkins, 2001; 331-343.
Hamza I, Faisst A, Prohaska JR, Chen J, Gruss P and Gitlin. JD. The metallochaperone Atox1 plays a critical role in perinatal copper homeostasis. Proc Natl Acad Sci. 2001; 98: 6848-6852 (Editorial)
Hamza I and Gitlin JD. Copper-transporting ATPases. In: The Encyclopedia of Molecular Medicine Ed. Creighton T. New York, John Wiley & Sons, 2002; 904-906
Hamza I and Gitlin JD. Hepatic Copper Transport. In: Molecular Pathogenesis of Cholestasis Ed. Trauner, M and Jansen P. Landes Bioscience, Austin, Texas 2002
Hamza I and Gitlin JD. Copper chaperones for cytochrome c oxidase and human disease. J Bioenerg Biomemb. 2002; 34:381-38
Hamza I, Prohaska JR, and Gitlin. JD. Essential Role for Atox1 in the Copper-Mediated Intracellular Trafficking of the Menkes ATPase. Proc Natl Acad Sci. 2003; 100:1215-1220