University of Kansas Medical Center 3901 Rainbow Blvd. , Lied 2034
Kansas City, KS 66160-7401
Phone: (913) 588-6935
Fax: (913) 588-7440
E-mail: gandrews@kumc.edu
Ph.D., Cell Biology, Baylor College of Medicine, Houston, Texas (1975-1978)
Our laboratory is interested in understanding the molecular mechanisms that regulate zinc homeostasis. Zinc is an essential metal required for the activity of hundreds of enzymes and transcription factors. A dietary deficiency of zinc causes a multitude of detrimental effects during pregnancy including malformation of the embryo, growth retardation and loss of pregnancy. Thus, understanding how zinc is taken into the embryonic environment and maintained there is of central importance. Zinc homeostasis is controlled by uptake, storage and excretion of this metal. One area of our research focuses on the transcription factor MTF-1. MTF-1 functions as a zinc-sensing transcription factor that regulates the expression of metallothionein and ZnT1 zinc transporter genes. These genes modulate the internal stores of zinc in the cell. We are interested in structure-function relationships in this essential protein. A second area of active research in our laboratory focuses on genes that encode zinc transporters in the ZIP superfamily. We are identifying and cloning mouse and human ZIP genes and then analyzing their structure, function and expression patterns in pregnant mice and embryos. We are also creating mice in which specific ZIP genes have been knocked out. These knockout mice are being examined to determine the physiological functions of these ZIP genes in zinc homeostasis during pregnancy.
Andrews, G.K., Lee, D-K., Ravindra, R., Lichtlen, P., Sirito, M., Sawadogo, M. and Schaffner. W. (2001) The transcription factors MTF-1 and USF1 cooperate to regulate mouse metallothionein-I gene expression in visceral endoderm cells during early development. EMBO. J. 20,1114-1122.
Daniels, P.J., Bittel, D., Smirnova, I.V., Winge, D.R., and Andrews, G.K. (2002) Mammalian metal response element-binding transcription factor-1 functions as a zinc-sensor in yeast, but not as a sensor of cadmium or oxidative stress, Nucl. Acids Res., 30, 3130-3140.
Jiang, H., Daniels, P.J., and Andrews, G.K. (2003) Putative zinc-sensing zinc-fingers of metal response element-binding transcription factor-1 stabilize a metal-dependent chromatin complex on the endogenous metallothionein-I promoter. J. Biol. Chem. 278, 30394-30402.
Dufner-Beattie, J., Wang, F., Kuo, Y-M., Gitschier, J., Eide, D., and Andrews, G.K. (2003) The acrodermatitis enteropathica gene ZIP4 encodes a tissue-specific, zinc regulated zinc transporter in mice. J. Biol. Chem. 278, 33474–33481.
Dufner-Beattie, J., Langmade, S.J., Wang, F., Eide, D., and Andrews, G.K., (2003) Structure, function, and regulation of a subfamily of mouse zinc transporter genes. J. Biol. Chem. 278, 50142–50150.
Daniels, P.J. and Andrews, G.K. (2003) Dynamics of the metal-dependent transcription factor complex in vivo at the mouse metallothionein-I promoter. Nucl. Acids Res. 31, 6710-6721.
Kim, B.E., Wang, F., Dufner-Beattie, J., Andrews, G.K., Eide, D.J., and Petris, M.J. (2004) Zn2+-stimulated endocytosis of the mZIP4 zinc transporter regulates its location at the plasma membrane. J. Biol. Chem. 279, 4523-4530.
Wang, F., Kim, B.E., Dufner-Beattie, J., Petris, M.J., Andrews, G.K., and Eide, D.J. (2004) Acrodermatitis Enteropathica mutations affect transport activity, localization, and zinc-responsive trafficking of the mouse ZIP4 zinc transporter. Human Mol. Gen. 13, 563-571.
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