Department of Biochemistry and Molecular Biology Baylor College of Medicine, Houston, TX, Ph.D., 1978
University of Calgary School of Medicine, Alberta, Canada (National Institutes of Health Postdoctoral Fellow)
National Institute of Environmental Health Sciences (Senior Staff Fellow)
The overall objective of my research program is to understand mechanisms that regulate the metabolism of essential and toxic metals in mammals. Specifically, we are interested in understanding the mechanism controlling homeostasis of the essential metal zinc, and in understanding how the toxic metal cadmium regulates the expression of protective genes. Three major research projects are underway in my laboratory. The first is designed to elucidate structure-function relationships in the transcription factor MTF-1.
This metal-sensing protein regulates the expression of genes that protect the organism against metal toxicity and oxidative stresses. A second project is designed to elucidate the structure, function and mechanisms of regulation of a subfamily of zinc transporter genes (ZIP1-3). We are employing gene knockout methodologies in mice, as well as molecular and biochemical approaches to address the roles of these genes in zinc metabolism. The third project is designed to create a mouse model of the human genetic disorder of zinc metabolism Acrodermatitis enteropathica. This genetic disease is caused by mutations in another zinc transporter gene (ZIP4), and we are exploring its structure, function and regulation.
Representative Publications
Dufner-Beattie, J., Huang, Z.L., Geiser, J., Xu, W. and Andrews, G.K., Mouse ZIP1 and ZIP3 genes together are essential for adaptation to dietary zinc deficiency during pregnancy. Genesis 44: 239-251, 2006.
Huang, Z.L, Dufner-Beattie, J. and Andrews,G.K., Expression and regulation of SLC39A family zinc transporters in the developing mouse intestine. Devel. Biol. 295: 571-579, 2006
Li, Y., Kimura, T., Latiy, J.H. and Andrews, G.K., The zinc-sensing mechanism of mouse MTF-1 involves linker peptides between the zinc fingers. Mol. Cell. Biol. 26: 5580-5587, 2006.
Dufner-Beattie, J., Huang, J.L., Geiser, J., Xu, W., and Andrews, G.K., Generation and Characterization of Mice Lacking the Zinc Uptake Transporter ZIP3. Mol. Cell. Biol. 25: 5607-5615, 2005.
Potter, B.M., Knudsen, N.A., Feng, L.S., Matskevich, V.A., Wilson, J.A., Andrews, G.K., and Laity, J.H., NMR assignment of the six zinc fingers of MTF-1 in the free and DNA bound states. J. Biomolecular NMR. 32: 94, 2005.
Potter, B.M., Feng, L., Parasuram, P., Matskevich, V.A., Wilson, J.A., Andrews, G.K. and Laity, J.H., The six zinc fingers of metal-response element-binding transcription factor-1 form stable and quasi-ordered structures with relatively small differences in zinc affinities. J. Biol. Chem. 280: 28529-28540, 2005.
Andrews, G.K., Wang, H., Dey, S.K. and Palmiter, R.D., The mouse zinc transporter 1 gene provides an essential function during early embryonic development. Genesis. 40: 74-81, 2004.
Dufner-Beattie, J., Kuo,Y-M., Gitschier, J. and Andrews, G.K., The adaptive response to dietary zinc in mice involves the differential cellular localization and zinc-regulation of the zinc transporters ZIP4 and ZIP5. J. Biol. Chem. 279: 49082-49090, 2004.
Jiang, H. and Andrews, G.K., Gene-Specific and Cell Type-Specific Effects of Signal Transduction Cascades on Metal-Regulated Gene Transcription Appear to Be Independent of Changes in the Phosphorylation of Metal Response Element-Binding Transcription Factor-1. Biochem J. 382: 33-41, 2004.
Wang, F., Kim, B.E., Dufner-Beattie, J., Petris, M.J., Andrews, G.K., and Eide, D.J., Acrodermatitis Enteropathica mutations affect transport activity, localization, and zinc-responsive trafficking of the mouse ZIP4 zinc transporter. Human Mol. Gen., 13: 563-571, 2004.
Wang, F., Dufner-Beattie, J., Kim, B.E., Petris, M.J., Andrews, G.K., and Eide, D.J., Zinc regulates mouse zinc-transporter mZIP1 and mZIP3 protein trafficking. J. Biol. Chem. 279: 24631 -24639, 2004.
Lee, D-K, Geiser, J., Dufner-Beattie, J. and Andrews, G.K., Pancreatic metallothionein plays a role in zinc homeostasis during maternal dietary zinc deficiency. J. Nutr., 133: 45-50, 2003.
Jiang, H., Daniels, P.J. and Andrews, G.K., 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, 2003.
Dufner-Beattie, J., Wang, F., Kuo, Y-M., Gitschier, J., Eide, D. and Andrews, G.K., The acrodermatitis enteropathica gene ZIP4 encodes a tissue-specific, zinc regulated zinc transporter in mice. J. Biol. Chem. 278: 33474 - 33481, 2003.
Dufner-Beattie, J., Langmade, S.J., Wang, F., Eide, D., and Andrews, G.K., Structure, function, and regulation of a subfamily of mouse zinc transporter genes. J. Biol. Chem. 278: 50142 - 50150, 2003.
Daniels, P.J. and Andrews, G.K., Dynamics of the metal-dependent transcription factor complex in vivo at the mouse metallothionein-I promoter. Nucl. Acids Res. 31: 6710 - 6721, 2003.
Daniels, P.J., Bittel, D., Smirnova, I.V., Winge, D.R. and Andrews, G.K., 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, 2002.
Johnson, D.A., Andrews, G.K. Xu, W. and Johnson, J.A., Activation of the antioxidant responsive element in primary cortical neuronal cultures derived from transgenic reporter mice. J. Neurochem., 81: 1233 - 1241, 2002.
Andrews, G.K., Lee, D-K., Ravindra, R., Lichtlen, P., Sirito, M., Sawadogo, M. and Schaffner. W., 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, 2001.
Andrews, G.K., Cellular zinc sensors: MTF-1 regulation of gene expression. Biometals, 14: 223-237, 2001.
Smirnova, I.V., Bittel, D.C., Ravindra, R., Jiang, H., and Andrews, G.K., Zinc and cadmium can promote rapid nuclear translocation of MTF-1. J. Biol. Chem., 275: 9377-9384, 2000.
Langmade, J. Ravindra, R., Daniels, P.J. and Andrews, G.K., The transcription factor MTF-1 mediates metal regulation of the mouse ZnT1 gene. J. Biol. Chem., 275: 34803-34809, 2000.
Bittel, D.B., Smirnova, I.V. and Andrews, G.K., Functional heterogeneity in the zinc fingers of the metalloregulatory transcription factor, MTF-1. J. Biol. Chem., 275: 37194 -37201, 2000.
Hernandez, J., Carrasco, J., Lee, D.K., Andrews, G.K., Bluthmann, H., and Hidalgo, J., IL-6 and TNF receptor 1 knockout mice reveal roles for IL-6 and TNF-alpha in liver metallothionein regulation during stress and inflammation. Cytokine, 12: 791-796, 2000.
Andrews,G.K. and Geiser, J., Expression of the metallothionein-I and -II genes provides a reproductive advantage during maternal dietary zinc deficiency. J. Nutr., 129: 1643-1648, 1999.
Lee, D.K., Carrasco, J., Hidalgo, J., and Andrews, G.K., Identification of a Signal Transducer and Activator of Transcription binding site in the mouse metallothionein-I promoter involved in interleukin-6 induced gene expression. Biochem. J., 337: 59-65, 1999.
Chu, W.A., Moehlenkamp, J.D., Bittel, D., Andrews, G.K., and Johnson, J.A., Cadmium-mediated activation of the metal response element in human neuroblastoma cells lacking functional metal response element-binding transcription factor-1, J. Biol. Chem., 274: 5279-5284, 1999.
Murphy, B.J., Andrews, G.K., Bittel, D, Disher, D.J., McCue, J., Green, C.J., Yanovsky, M., Giaccia, A., Sutherland, R.M., Laderoute, R., and Webster, K., Activation of metallothionein gene expression by hypoxia involves metal response elements and MTF-1. Cancer Res., 59: 1315-1322, 1999.
Bittel, D., Dalton, T., Samson, S.L.-A, Gedamu, L., and Andrews, G.K., The DNA-binding activity of MRE-binding transcription factor-1 is activated in vivo and in vitro by Zn, but not by other transition metals. J. Biol Chem., 273: I7127-7133, 1998
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