Alex J. Lange, PhD

Current Position (s): Assistant Professor, Department of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota Medical School

Research Interests and areas of potential collaboration:
Therapeutic intervention in diabetes via manipulation of carbohydrate metabolism enzymes and their genes.

Selected publications:

Manzano, A., Xavier Perez, J., Nada, M., Estivill, X., Lange, A.J., and Bartrons, R. (1999). Cloning, Expression and chromosomal localization of human testis of 6-Phosphofructo-2-kinase/fructose-2,6-bisphosphatase Gene. Gene, In press.

Okar, D.A, and Lange, A.J. (1999). Fructose-2,6-bisphosphatase and Control of Carbohydrate Metabolism in Eukaryotes. Biofactors, In press.

Nordlie, R. C., Foster, J., and Lange, A.J. (1999). Regulation of Glucose Production by the Liver. Ann. Rev. of Nutr., In press.

Miller, S., Karschnia, E., Anand, G., Bell, G.I., Laporte, D., and Lange, A.J. (1999). Characterization of Glucokinase Mutations Associated with Maturity Onset Diabetes in the Young Type 2 (MODY-2): Different Glucokinase Defects Lead to a Common Phenotype. Diabetes, Submitted.

Zhao, Z., Wendt, C.H., Sharma, R., Lange, A.J., Ingbar, D.H. (1999). Transcriptional Regulation of Rat Na+-K+ ATPase Beta-1 Subunit Gene by an Intronic Sequence and Glucocorticoids. Gene, Submitted.

Okar, D.A., Live, D.H., Kirby, T.L., Karschnia, E.J., von Weymarn, L., Armitage, I.M. and Lange, A.J. (1999) The Roles of Glu-327 and His-446 in the Bisphosphatase Reaction of Rat Liver 6-Phosphofructo-2-kinase/Fructose-2,6-bisphosphatase Probed by NMR Spectroscopic and Mutational Analyses of the Enzyme in the Transient Phosphohistidine Intermediate Complex. Biochemistry, web release date 3-18-99.

Trinh, K.Y., O'Doherty, R.M., Anderson, P., Lange, A.J., Newgard, C.B. (1998) Perturbation of fuel homeostasis caused by overexpression of the glucose-6-phosphatase catalytic subunit in liver of normal rats. J. Biol. Chem. 273(47):31615-20.

Heine-Suner, D., Diaz-Guillen, M.A., Lange, A.J., Rodriguez de Cordoba, S. (1998) Sequence and structure of the human 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase heart isoform gene (PFKFB2). Eur. J. Biochem. 254(1):103-10.

Okar, D. A., Lee, Y. -H, Argaud, D., McFarlan, S.C., and Lange, A.J. (1998). The 6-Phosphofructo-2-kinase/fructose-2,6-bisphosphatase system: Regulation by Insulin and an Insulinomimetic Approach to Lowering Blood Glucose Levels. Frontiers in Diabetes Belfiore F; Lorenzi, M., Molinatti, G.M., and Porta, M. (eds) S. Karger AG, Basel, Vol. 14, pp 30-46.

Okar, D.A., Felicia, N.D., Gui, L., Lange, A.J. (1997) Labeling of recombinant protein for NMR spectroscopy: global and specific labeling of the rat liver fructose 2,6-bisphosphatase domain. Protein. Expr. Purif. 11(1):79-85.

Argaud, D., Kirby, T., Newgard, C.B., and Lange, A.J. (1997). Glucose and Fructose-2,6-bisphosphate Stimulation of Glucose-6-phosphatase Gene Expression in Fao Rat Hepatoma Cells. J. Biol. Chem. 272: 12854-12861.

McFarlan, S.C., Zhang, Q., Miksicek, R.J., and Lange, A.J. (1997). Characterization of an Intronic Hormone Response Element of the Rat Liver/Skeletal Muscle 6-Phosphofructo-2-kinase/fructose-2,6-bisphosphatase Gene. Mol Cell. Endocrinol. 129: 219-227.

Lee, Y.-H., Olson, T.W., Ogata, C., Levitt, D.G., Banaszak. L., and Lange, A.J. (1997). Crystal Structure of an Active Phospho-enzyme Intermediate of Rat Liver Fructose-2,6-bisphosphatase: Implications for Kinetic Mechanism. Nature Structural Biology 4: 615-619

Trinh, K., Minassian, C., Lange, A.J., and Newgard, C.B. (1997). Expression of the Catalytic Subunit of Glucose-6-phosphatase in INS-1 Cells: Effects on Glucose Cycling, Glucose Usage, and Insulin Secretion. J. Biol. Chem. 272:24837-24842.

Seone, J., Trinh, K., O’Doherty, R.M., Gome-Foix, A.M., Lange, A.J., Newgard, C.B., and Guinovart, J.J. (1997). Metabolic Impact of Adenovirus-Mediated Overexpression of the Glucose-6-Phosphatase Catalytic Subunit in Hepatocytes. J. Biol. Chem. 272: 24837-24842.

Argaud, D., Zhang, Q., Maitra, S.R., Pan, W., Pilkis, S.J., and Lange, A.J. (1996). Isolation and Characterization of Rat Liver Glucose-6-phosphatase Gene: Regulation of Gene Expression in Different Endocrine and Nutritional States. Diabetes 45: 1563-1571.

Jaoquin, M., Salvado, C., Bellosilo, B., Gil, J., Lange, A.J., and Tauler, A. (1996). Effect of Growth Factors on the Expression of 6-Phosphofructo-2-kinase/fructose-2,6-bisphosphatase in Rat-1 Fibroblasts. J. Biol. Chem. 272: 2846-2851.

Okar, DA, Kakalis, LT, Narula, SS, Armitage, IM, Pilkis, SJ, (1995), Biochemical Journal, 308, 189-195. Identification of transient intermediates in the bisphosphatase reaction of rat liver 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase by 31P-NMR spectroscopy.

Li, L., Yao, W., Lange, A.J., Pilkis, S.J., Dong, M., Yin, Y., and Xu, G. (1995). Expression of Chicken Liver 6-Phosphofructo-2-kinase/fructose-2,6-bisphosphatase and its Bisphosphatase Domain in Escherichia coli. Biochem. Biophys. Res. Comm. 209: 883-893.

Pilkis, S.J., Claus, T., Kurland, I.J., and Lange, A.J. (1995). 6-Phosphofructo-2-kinase/Fructose-2,6-bisphosphatase: A Metabolic Signaling Enzyme. Ann. Rev. Biochem. 64: 799-835.

Scott, P., Lange, A.J., Pilkis, S.J., and Kruger, N.J. (1995). Carbon Metabolism in Leaves of Transgenic Tobacco (Nicotiana tabacum) Containing Elevated Fructose 2,6-Bisphosphate Levels. Plant J. 7 : 461-469.

Argaud, D., Lange, A.J., Becker, T.C., Okar, D.A., El-Maghrabi, M.R., Newgard, C.B., and Pilkis, S.J. (1995). Adenovirus-mediated Overexpression of Liver 6-Phosphofructo-2-kinase/fructose-2,6-bisphosphatase in Gluconeogenic Rat Hepatoma Cells: Paradoxical Effect on Fru-2,6-P2 Levels, J. Biol. Chem. 270 (41): 24229-24236.

Ventura, F., Ambrosio, S., Bartrons, R., El-Maghrabi, M.R., Lange, A.J., and Pilkis, S.J. (1995). Isolation of a cDNA for Bovine Brain 6-Phosphofructo-2-kinase/fructose-2,6-bisphosphatase. Biochem. Biophys. Res. Comm. 209: 1140-1148.

El-Maghrabi, M.R., Lange, A.J., Jiang, W., Yamagata, K., Stoffel, M., Takeda, J., Fernald, A.A., Le Beau, M.M., Bell, G.I., Baker, L., and Pilkis, S.J. (1995). Human Fructose-1-bisphosphatase Gene (FBP1): Exon-Intron Organization, Localization to Chromosome Bands 9q22.2-q22.3, and Mutation Screening in Subjects with Fructose-1-bisphosphatase Deficiency. Genomics 27: 520-525.

Lange, A.J., Argaud, D., El-Maghrabi, M.R., Pan, W., Maitra, S.R., and Pilkis, S.J. (1994). Isolation of a cDNA for the Catalytic Subunit of Rat Liver Glucose-6-Phosphatase: Regulation of Gene Expression by Insulin, Dexamethasone and cAMP. Biochem. Biophy. Res. Comm. 201:302-309.

Maitra, S.R., Pan, W., Lange, A.J., El-Maghrabi, M.R., Abumrad, N.N., and Pilkis, S.J. (1994). Glucose-6-phosphatase Gene Expression and Activity are Modulated in Hemorrhagic Shock: Evidence for a New Heat-Sensitive Activator. Biochem. Biophy. Res. Comm. 204: 716-724.