The VICC.ORG Directory of Doctors, Healthcare Providers & Researchers
Conrad Wagner, Ph.D.
Professor of Biochemistry
VICC Member
Researcher
Contact Information:
Vanderbilt University Medical Center
620 Light Hall
Nashville, TN 37232-0146
615-343-9866
Research Specialty
Research Specialty: Metabolism of one-carbon compounds
Research Description
Research Description: Our laboratory has been involved with various aspects of one-carbon metabolism for many years. These include the roles of the coenzyme forms of the vitamin, folic acid, and the enzymes that carry out these functions. Our approach has been to investigate every available aspect of Biochemistry to accomplish this including enzymology, mass spectrometry, crystallography, molecular biology and nutritional manipulation.
Our latest work has focused on developing a mouse knock-out of the enzyme GNMT which is responsible for the regulation of levels of S-adenosymethionine (SAM). This GNMT knockout mouse spontaneously develops fatty liver and hepatocellular carcinoma that is a result of methylation of tumor suppressors in the promoter region of the gene. SAM, a metabolic product of methionine metabolism, is the major donor of methyl groups in the body. This line of investigation has led us to the discovery of two new metabolic diseases. We have recently shown that the histone demethylase, LSD1, is a folate binding protein in which the folate probably serves to scavenge the formaldehyde that is a product of the demethylase reaction. This finding suggests that the levels of folate in the diet can play a role in gene expression. More recently we have shown that products of methionine breakdown in serum may serve as markers for the risk of developing metastasis of prostate cancer.
Publications
- Luka, Z, Moss, F, Loukachevitch, LV, Bornhop, DJ, Wagner, C Histone demethylase LSD1 is a folate-binding protein. Biochemistry, 50(21), 4750-6, 2011.
- Wagner, C, Fredi, J, Bick, J, McPherson, J Monitoring myocardial recovery during induced hypothermia with a disposable monoplane TEE probe. Resuscitation, 82(3), 355-7, 2011.
- Wagner, CE, Bick, JS, Webster, BH, Selby, JH, Byrne, JG Use of a Miniaturized Transesophageal Echocardiographic Probe in the Intensive Care Unit for Diagnosis and Treatment of a Hemodynamically Unstable Patient After Aortic Valve Replacement. J Cardiothorac Vasc Anesth, 2011.
- Shrubsole, MJ, Yang, G, Gao, YT, Chow, WH, Shu, XO, Cai, Q, Rothman, N, Gao, J, Wagner, C, Zheng, W Dietary B vitamin and methionine intakes and plasma folate are not associated with colorectal cancer risk in Chinese women. Cancer Epidemiol Biomarkers Prev, 18(3), 1003-6, 2009.
- Luka, Z, Mudd, SH, Wagner, C Glycine N-methyltransferase and regulation of S-adenosylmethionine levels. J Biol Chem, 284(34), 22507-11, 2009.
- Luka, Z, Loukachevitch, LV, Wagner, C Acetylation of N-terminal valine of glycine N-methyltransferase affects enzyme inhibition by folate. Biochim Biophys Acta, 1784(9), 1342-6, 2008.
- Luka, Z, Pakhomova, S, Loukachevitch, LV, Egli, M, Newcomer, ME, Wagner, C 5-methyltetrahydrofolate is bound in intersubunit areas of rat liver folate-binding protein glycine N-methyltransferase. J Biol Chem, 282(6), 4069-75, 2007.
- Capdevila, A, Burk, RF, Freedman, J, Frantzen, F, Alfheim, I, Wagner, C A simple rapid immunoassay for S-adenosylhomocysteine in plasma. J Nutr Biochem, 18(12), 827-31, 2007.
- Luka, Z, Pakhomova, S, Luka, Y, Newcomer, ME, Wagner, C Destabilization of human glycine N-methyltransferase by H176N mutation. Protein Sci, 16(9), 1957-64, 2007.
- Wagner, C, Koury, MJ S-Adenosylhomocysteine: a better indicator of vascular disease than homocysteine. Am J Clin Nutr, 86(6), 1581-5, 2007.
- Luka, Z, Capdevila, A, Mato, JM, Wagner, C A glycine N-methyltransferase knockout mouse model for humans with deficiency of this enzyme. Transgenic Res, 15(3), 393-7, 2006.
- Luka, Z, Ham, AJ, Norris, JL, Yeo, EJ, Yermalitsky, V, Glenn, B, Caprioli, RM, Liebler, DC, Wagner, C Identification of phosphorylation sites in glycine N-methyltransferase from rat liver. Protein Sci, 15(4), 785-94, 2006.
- Jabs, K, Koury, MJ, Dupont, WD, Wagner, C Relationship between plasma S-adenosylhomocysteine concentration and glomerular filtration rate in children. Metabolism, 55(2), 252-7, 2006.
- Luka, Z, Wagner, C Effect of naturally occurring mutations in human glycine N-methyltransferase on activity and conformation. Biochem Biophys Res Commun, 312(4), 1067-72, 2003.
- Luka, Z, Wagner, C Expression and purification of glycine N-methyltransferases in Escherichia coli. Protein Expr Purif, 28(2), 280-6, 2003.
- Luka, Z, Wagner, C Human glycine N-methyltransferase is unfolded by urea through a compact monomer state. Arch Biochem Biophys, 420(1), 153-60, 2003.
- Luka, Z, Cerone, R, Phillips, JA, Mudd, HS, Wagner, C Mutations in human glycine N-methyltransferase give insights into its role in methionine metabolism. Hum Genet, 110(1), 68-74, 2002.
- Kerins, DM, Koury, MJ, Capdevila, A, Rana, S, Wagner, C Plasma S-adenosylhomocysteine is a more sensitive indicator of cardiovascular disease than plasma homocysteine. Am J Clin Nutr, 74(6), 723-9, 2001.
- Krupenko, SA, Wagner, C Aspartate 142 is involved in both hydrolase and dehydrogenase catalytic centers of 10-formyltetrahydrofolate dehydrogenase. J Biol Chem, 274(50), 35777-84, 1999.
- Yeo, EJ, Briggs, WT, Wagner, C Inhibition of glycine N-methyltransferase by 5-methyltetrahydrofolate pentaglutamate. J Biol Chem, 274(53), 37559-64, 1999.
- Pattanayek,R., Wagner,C. and Newcomer,M.E " Crystal Structure of Apo- Glycine N-methyltransferase ." Protein Science, 71326-1331, 1998.
- Krupenko,S. and Wagner,C " Overexpression of Functional Hydrolase Domain of 10-Formyltetrahydrofolate Dehydrogenase in E coli ." Protein Expression and Purification, (14), 145-152, 1998.
- Pattanayek, R, Newcomer, ME, Wagner, C Crystal structure of apo-glycine N-methyltransferase (GNMT). Protein Sci, 7(6), 1326-31, 1998.
- Capdevila, A, Wagner, C Measurement of plasma S-adenosylmethionine and S-adenosylhomocysteine as their fluorescent isoindoles. Anal Biochem, 264(2), 180-4, 1998.
- Krupenko, SA, Wagner, C Overexpression of functional hydrolase domain of rat liver 10-formyltetrahydrofolate dehydrogenase in Escherichia coli. Protein Expr Purif, 14(1), 146-52, 1998.
- Krupenko,S.A., Wagner,C. and Cook,R.J " Domain Structure of Rat 10- formyltetrahydrofolate Dehydrogenase: Resolution of the Amino-terminal Domain as 10- formyltetrahydrofolate Hydrolase. ." J. Biol. Chem., 27210273-, 1997.
- Krupenko,S.A., Wagner,C. and Cook,R.J " Expression, Purification and Properties of the Aldehyde Dehydrogenase Homologous Carboxyl-terminal Domain of Rat 10- formyltetrahydrofolate Dehydrogenase ." J. Biol. Chem., 27210266-10272, 1997.
- Capdevila,A., Decha-Umphai,W., Song, K.-H., Borchardt,R.T. and Wagner,C " Pancreatic Exocrine Secretion is Blocked by Inhibitors of Methylation ." Arch. Biochem. Biophys, 34547-55, 1997.
- Krupenko,N. and Wagner,C " Transport of Rat Liver Glycine N- methyltransferase Into Rat Liver Nuclei ." J. Biol. Chem., 27227140-27146, 1997.
- Horne,D.W., Holloway,R.S. and Wagner,C " Transport of S- adenosylmethionine in Isolated Rat Liver Mitochondria. ." Arch. Biochem. Biophys., 343201-206, 1997.
- Krupenko, SA, Wagner, C, Cook, RJ Domain structure of rat 10-formyltetrahydrofolate dehydrogenase. Resolution of the amino-terminal domain as 10-formyltetrahydrofolate hydrolase. J Biol Chem, 272(15), 10273-8, 1997.
- Krupenko, SA, Wagner, C, Cook, RJ Expression, purification, and properties of the aldehyde dehydrogenase homologous carboxyl-terminal domain of rat 10-formyltetrahydrofolate dehydrogenase. J Biol Chem, 272(15), 10266-72, 1997.
- Capdevila, A, Decha-Umphai, W, Song, KH, Borchardt, RT, Wagner, C Pancreatic exocrine secretion is blocked by inhibitors of methylation. Arch Biochem Biophys, 345(1), 47-55, 1997.
- Krupenko, NI, Wagner, C Transport of rat liver glycine N-methyltransferase into rat liver nuclei. J Biol Chem, 272(43), 27140-6, 1997.
- Wagner, C Symposium on the subcellular compartmentation of folate metabolism. J Nutr, 126(4 Suppl), 1228S-34S, 1996.
- Wagner, C, Briggs, WT, Horne, DW, Cook, RJ 10-Formyltetrahydrofolate dehydrogenase: identification of the natural folate ligand, covalent labeling, and partial tryptic digestion. Arch Biochem Biophys, 316(1), 141-7, 1995.
- Krupenko, SA, Horstman, DA, Wagner, C, Cook, RJ Baculovirus expression and purification of rat 10-formyltetrahydrofolate dehydrogenase. Protein Expr Purif, 6(4), 457-64, 1995.
- Krupenko, SA, Wagner, C, Cook, RJ Cysteine 707 is involved in the dehydrogenase activity site of rat 10-formyltetrahydrofolate dehydrogenase. J Biol Chem, 270(2), 519-22, 1995.
- Cook, RJ, Wagner, C Enzymatic activities of rat liver cytosol 10-formyltetrahydrofolate dehydrogenase. Arch Biochem Biophys, 321(2), 336-44, 1995.
- Krupenko, SA, Wagner, C, Cook, RJ Recombinant 10-formyltetrahydrofolate dehydrogenase catalyses both dehydrogenase and hydrolase reactions utilizing the synthetic substrate 10-formyl-5,8-dideazafolate. Biochem J, 306 ( Pt 3)651-5, 1995.
- Yeo, EJ, Wagner, C Tissue distribution of glycine N-methyltransferase, a major folate-binding protein of liver. Proc Natl Acad Sci U S A, 91(1), 210-4, 1994.
- Balaghi, M, Wagner, C DNA methylation in folate deficiency: use of CpG methylase. Biochem Biophys Res Commun, 193(3), 1184-90, 1993.
- Balaghi, M, Horne, DW, Wagner, C Hepatic one-carbon metabolism in early folate deficiency in rats. Biochem J, 291 ( Pt 1)145-9, 1993.
- Balaghi, M, Horne, DW, Woodward, SC, Wagner, C Pancreatic one-carbon metabolism in early folate deficiency in rats. Am J Clin Nutr, 58(2), 198-203, 1993.
- Balaghi, M, Wagner, C Methyl group metabolism in the pancreas of folate-deficient rats. J Nutr, 122(7), 1391-6, 1992.
- Yeo, EJ, Wagner, C Purification and properties of pancreatic glycine N-methyltransferase. J Biol Chem, 267(34), 24669-74, 1992.
- Cook, RJ, Lloyd, RS, Wagner, C Isolation and characterization of cDNA clones for rat liver 10-formyltetrahydrofolate dehydrogenase. J Biol Chem, 266(8), 4965-73, 1991.
- Wickwire, BM, Wagner, C, Broquist, HP Pipecolic acid biosynthesis in Rhizoctonia leguminicola. II. Saccharopine oxidase: a unique flavin enzyme involved in pipecolic acid biosynthesis. J Biol Chem, 265(25), 14748-53, 1990.
- Horne, DW, Cook, RJ, Wagner, C Effect of dietary methyl group deficiency on folate metabolism in rats. J Nutr, 119(4), 618-21, 1989.
- Cook, RJ, Horne, DW, Wagner, C Effect of dietary methyl group deficiency on one-carbon metabolism in rats. J Nutr, 119(4), 612-7, 1989.
- Wagner, C, Decha-Umphai, W, Corbin, J Phosphorylation modulates the activity of glycine N-methyltransferase, a folate binding protein. In vitro phosphorylation is inhibited by the natural folate ligand. J Biol Chem, 264(16), 9638-42, 1989.
You do not have JavaScript enabled. This site works better with JavaScript turned on.
