Patrick J. Stover
Professor & Division Director

Patrick J. Stover

Phone

607 255-8001
(Fax) 607 254-5177

Address

Division of Nutrition
127 Savage Hall
Cornell University
Ithaca, NY 14853-2703

Email

Web Sites

Department Profile

Background

Patrick Stover received his Bachelors of Science degree in Chemistry from Saint Joseph's University in 1987, and his PhD degree in Biochemistry and Molecular Biophysics in 1990 from the Medical College of Virginia.  He conducted his postdoctoral research at the University of California at Berkeley in Nutritional Sciences from 1991 to 1994.  He became an Assistant Professor of Nutritional Biochemistry in 1994 at Cornell University and currently serves as Professor and Director of the Division of Nutritional Sciences at Cornell University.

The Stover laboratory studies the biochemical mechanisms that underlie pathologies that have interactive genetic and nutritional components. Current research is focused on studying the role of folic acid metabolism in diseases including neural tube defects, cardiovascular disease, epithelial cancer and neurological disorders.  We have cloned several human genes that encode enzymes involved in folate metabolism, and are studying their regulation and influence on folate metabolism and cellular homeostasis.  To that end, we use molecular-genetic approaches to generate human cell lines and transgenic mouse lines that serve as models for known genetic diseases.  We study these models to determine the relationships among folate status and disruptions in folate metabolism, and their effects on genome expression and stability in health and disease.  Results from these studies will lead to new strategies and interventions to prevent folate-related pathologies. My teaching interests are focused on the regulation of metabolic biochemistry and nutrient availability during development and in disease states.

Research Description

Regulation of folic acid-mediated one-carbon metabolism, SUMO-dependent nuclear folate metabolism and genome stability; methyl group metabolism in colon cancer and neural tube defects.

Publications

  • Beaudin, AE, Perry, CA, Stabler, SP, Allen, RH, and Stover, PJ 2012 Maternal Mthfd1 disruption impairs fetal growth but does not cause NTDs in mice. Amer. J. Clin Nutr. In press
  • Anderson, DD, Woeller, CF, Chiang, E-P, Shane, B, and Stover, PJ 2012 SHMT1 and SHMT2 anchor the nuclear de novo thymidylate synthesis pathway to the nuclear lamina for DNA replication and repair. J. Biol. Chem. In press.
  • Anderson, DD, Eom, JY and Stover, PJ 2011 Competition between sumoylation and ubiquitylation of serine Hydroxymethyltransferase 1 determines its nuclear localization and its accumulation in the nucleus. J. Biol. Chem. In press. PMID: 22194612
  • Wernimont SM, Clark AG, Stover PJ, Wells MT, Litonjua AA, Weiss ST, Gaziano JM, Tucker KL, Baccarelli A, Schwartz J, Bollati V, Cassano PA. 2011 Folate network genetic variation, plasma homocysteine, and global genomic methylation content: a genetic association study. BMC Med Genet. Nov 21;12(1):150. PMID: 22103680
  • MacFarlane, AJ, Anderson, DD, Flodby, P, Perry, CA, Allen, RA, Stabler, SP, and Stover, PJ 2011 Nuclear localization of the de novo thymidylate biosynthesis pathway is required to prevent uracil accumulation in DNA. J. Biol. Chem. 286(51):44015-22. PMID: 22057276
  • Beaudin, AE, Abarinov, EV, Malysheva, O, Perry, CA, Caudill, M, Stover, PJ 2012 Dietary folate but not choline modifies neural tube defect risk in Shmt1 knock-out mice. Amer. J. Clin. Nutr. 95(1):109-14. PMID: 22134951
  • Anderson, DD, Quintero, CM and Stover, PJ 2011 Identification of a de novo thymidylate biosynthesis pathway in mammalian mitochondria. Proc. Natl. Acad. Sci. 108(37):15163-8. PMID: 21876188
  • Field, MS, Anderson, DD, and Stover, PJ 2011 Mthfs is an essential gene in mice and a component of the purinosome. Front. Gene. 2:36.
  • Beaudin, AE, Abarinov, EV, Noden, DM, Perry, CA, Chu, S, Stabler, SP, Allen, RH and Stover, P J 2011 Shmt1 and de novo thymidylate biosynthesis underlie folate-responsive neural tube defects in mice. Am. J. Clin. Nutr. 93(4):789-98. PMID: 21346092
  • Wernimont, SM, Clark, AG, Stover, PJ, Wells, MT, Litonjua, AA, Weiss, ST, Gaziano, JM, Tucker, KL, Baccarelli, A, Schwartz, J, Bollati, V, and Cassano, PA 2011 Folate network genetic 1 variation, plasma homocysteine, and global genomic methylation content. J Nutr. 141(2):255-60. PMID: 21178087
  • MacFarlane AJ, Perry, CA, McEntee, MF, Lin, DM, and Stover, PJ 2011 Mthfd1 is a Modifier of Chemically-induced Intestinal Carcinogenesis. Carcinogenesis 32(3):427-33. PMID: 21156972
  • Wernimont, SM, Raiszadeh, F, Stover, PJ, Rimm, E, Hunter, D, Tang, W and Cassano, PA 2011 Polymorphisms in Serine Hydroxymethyltransferase 1 and Methylenetetrahydro-folate Reductase Interact to Increase Cardiovascular Disease Risk in Humans. J Nutr. 141(2):255-60. PMID: 21178087
  • MacFarlane AJ, Perry, CA, McEntee, MF, Lin, DM, and Stover, PJ 2011 Shmt1 Heterozygosity Impairs Folate-Dependent Thymidylate Synthesis Capacity and Modifies Risk of Apcmin-Mediated Intestinal Cancer Risk. Can Res. 71(6):2098-107. PMID: 21406397
  • Ching, Y-H, Munroe, RJ, Moran, JL, Barker, AK, Mauceli, E, Fennell, T., diPalma, F., Lindblad-Toh, K., Abcunas, Gilmour, JF, LM, Harris, TP, Kloet, SL, Luo, Y, McElwee, J, Mu, W, Park, HK, Rogal, DL, Schimenti, KJ, Shen, L, Shindo, M, Shou, JY, Stenson, EK, Stover, PJ and Schimenti, JC 2010 High Resolution Mapping and Positional Cloning of ENU-induced Mutations in the Rw region of Mouse Chromosome 5. BMC Genet. 11(1):106. PMID: 21118569
  • Stover, PJ, Harlan, WR, Hammond, JA, Hendershot, T, Hamilton, CM 2010 PhenX: An Interdisciplinary Toolkit for Genetics and Epidemiology. Curr Opin Lipidol. 21(2):136-40. PMID: 20154612
  • Bentley, AR, Raiszadeh, F, Stover, PJ, Hunter, DJ, Hankinson, SE, and Cassano, PA 2010 No association between cSHMT genotypes and the risk of breast cancer in the Nurses' Health Study. Eur J Clin Nutr. 64(1):108-10. PMID: 19707223
  • Fox, JT, Shin, WK, Caudill, MA and Stover, PJ 2009 A UV-Responsive Internal Ribosome Entry Site Enhances Cytoplasmic Serine Hydroxymethyltransferase Expression for DNA Damage Repair. J. Biol. Chem. 284(45):31097-108. PMID: 19734144
  • Fox, JT and Stover, PJ 2009 Mechanism of the Internal Ribosome Entry Site-mediated Translation of Serine Hydroxymethyltransferase 1. J. Biol. Chem. 284(45):31085-96. PMID: 19734143
  • Anderson, DD and Stover, PJ 2009 SHMT1 and SHMT2 are Functionally Redundant in Nuclear de novo Thymidylate Biosynthesis. PLoS One Jun 9;4(6):e5839. PMID: 19513116
  • MacFarlane AJ, Perry CA, Girnary HH, Gao D, Allen RH, Stabler SP, Shane B, and Stover PJ. 2009. Mthfd1 is an Essential Gene in Mice and Alters Biomarkers of Impaired One-Carbon Metabolism. J. Biol. Chem. 284(3):1533-9. PMID: 19033438
  • Field MS, Anguera MC, Page R and Stover PJ. 2009. 5,10-Methenyltetrahydrofolate Synthetase Activity is Increased in Tumors and Modifies the Efficacy of Antipurine LY309887. Arch. Biochem. Biophys. 481(2):145-50. PMID: 19022216
  • Anguera, M. C. and Stover, P. J. (2006) Methenyltetrahydrofolate Synthetase is a High-Affinity Catecholamine-Binding Protein. Arch. Biochem. Biophys. 455(2):175-87.
  • Anguera MC, Field MS, Perry C, Ghandour H, Chiang EP, Selhub J, Shane B, Stover PJ. (2006) Regulation of folate-mediated one-carbon metabolism by 10-formyltetrahydrofolate dehydrogenase. J. Biol Chem. 281(27):18335-42.
  • Stover PJ (2006) Influence of human genetic variation on nutritional requirements. Am J Clin Nutr Feb;83(2):436S-442S.
  • Field MS, Szebenyi DM, Stover PJ (2006) Regulation of de novo purine biosynthesis by methenyltetrahydrofolate synthetase in neuroblastoma. J Biol Chem Feb 17;281(7):4215-4221.
  • Perry C, Sastry R, Nasrallah IM, Stover PJ (2005) Mimosine attenuates serine hydroxymethyltransferase transcription by chelating zinc. Implications for inhibition of DNA replication. J Biol Chem Jan 7;280(1):396-400.
  • Lim U, Peng K, Shane B, Stover PJ, Litonjua AA, Weiss ST, Gaziano JM, Strawderman RL, Raiszadeh F, Selhub J, Tucker KL, Cassano PA (2005) Polymorphisms in cytoplasmic serine hydroxymethyltransferase and methylenetetrahydrofolate reductase affect the risk of cardiovascular disease in men. J Nutr Aug;135(8):1989-1994.
  • Stover PJ (2005) Ferritin and serine hydroxymethyltransferase. In: Nutrient and Gene Interactions in Cancer (Shils ME, ed.) Chapter 11. CRC Press (in press)
  • Anguera MC, Liu X, Stover PJ (2004) Cloning, expression, and purification of 5,10-methenyltetrahydrofolate synthetase from Mus musculus. Prot Expr Purif Jun;35(2):276-283.
  • Stover PJ (2004) Nutritional genomics. Physiol Genomics Jan 15;16(2):161-165. Review.
  • Stover PJ (2004) Physiology of folate and vitamin B12 in health and disease. Nutr Rev Jun;62(6 Pt 2):S3-12; discussion S13. Review.
  • Anguera MC, Suh JR, Ghandour H, Nasrallah IM, Selhub J, Stover PJ (2003) Methenyltetrahydrofolate synthetase regulates folate turnover and accumulation. J Biol Chem Aug 8;278(32):29856-29862.
  • Zanetti KA, Stover PJ (2003) Pyridoxal phosphate inhibits dynamic subunit interchange among serine hydroxymethyltransferase tetramers. J Biol Chem Mar 21;278(12):10142-10149.
  • Garza C, Stover P (2003) The role of science in identifying common ground in the GMO debate. Trend Food Tech 14:182-190.
  • Stover PJ (2003) New paradigms for nutrient control of genome translation. Nutr Rev Dec;61(12):427-431. Review. 
  • Herbig K, Chiang EP, Lee LR, Hills J, Shane B, Stover PJ (2002) Cytoplasmic serine hydroxymethyltransferase mediates competition between folate-dependent deoxyribonucleotide and S-adenosylmethionine biosyntheses. J Biol Chem Oct 11;277(41):38381-38389. Epub 2002 Aug 2. 
  • Stover PJ, Garza C (2002) Molecular and genetic considerations for long-term nutrition interventions. Asia Pacific J Clin Nutr 11(S6):S129-S136.
  • Stover PJ, Garza C. (2002) Bringing individuality to public health recommendations. J Nutr Aug;132(8 Suppl):2476S-2480S. Review.
  • Stover PJ (2002) Nutrition and developmental biology. Annales Nestle 60(1):1-11. 
  • Allen LH, Bentley ME, Donovan SM, Ney DM, Stover PJ (2002) Securing the future of nutritional sciences through integrative graduate education. J Nutr Apr;132(4):779-784.
  • Herbig AK, Girgis S, Stover PJ (2002) Effects of cellular glycine concentration on human cell proliferation in culture. In: Chemistry and Biology of Pteridines and Folates (Milstein S, Kapatos G, Levine RA, Shane B, eds.). Kluwer Academic Publishers, Boston. pp. 491-494. 
  • Anguera M, Stover PJ (2002) Rapid affinity purification of the T-protein from rabbit liver. In: Chemistry and Biology of Pteridines and Folates (Milstein S, Kapatos G, Levine RA, Shane B, eds.). Kluwer Academic Publishers, Boston. pp. 485-490. 
  • Stover PJ (2002) Regulation of folate metabolism by iron. In: Folate and Human Development, Massaro EL, Rogers JM, eds. Humana Press, New Jersey pp. 241-262.
  • Oppenheim EW, Adelman C, Liu X, Stover PJ (2001) Heavy chain ferritin enhances serine hydroxymethyltransferase expression and de novo thymidine biosynthesis. J Biol Chem Jun 8;276(23):19855-19861. Epub 2001 Mar 12.
  • Liu X, Szebenyi DM, Anguera MC, Thiel DJ, Stover PJ (2001) Lack of catalytic activity of a murine mRNA cytoplasmic serine hydroxymethyltransferase splice variant: evidence against alternative splicing as a regulatory mechanism. Biochemistry Apr 24;40(16):4932-4939.
  • Hirschberger LL, Daval S, Stover PJ, Stipanuk MH (2001) Murine cysteine dioxygenase gene: structural organization, tissue-specific expression and promoter identification. Gene Oct 17;277(1-2):153-161.
  • Zhao R, Chen Y, Tan W, Sharma A, Stover PJ, Rosowsky A, Deth RC (2001) Relationship between dopamine-stimulated phospholipid methylation and single-carbon folate pathway. J Neurochem 78:788-796. 
  • Suh JR, Herbig AK, Stover PJ (2001) New perspectives on folate catabolism. Annu Rev Nutr 21:255-282. Review.
  • Oppenheim EW, Nasrallah IM, Mastri MG, Stover PJ (2000) Mimosine is a cell-specific antagonist of folate metabolism. J Biol Chem Jun 23;275(25):19268-19274. 
  • Liu X, Reig B, Nasrallah IM, Stover PJ (2000) Human cytoplasmic serine hydroxymethyltransferase is an mRNA binding protein. Biochemistry Sep 26;39(38):11523-11531. 
  • Szebenyi DM, Liu X, Kriksunov IA, Stover PJ, Thiel DJ (2000) Structure of a murine cytoplasmic serine hydroxymethyltransferase quinonoid ternary complex: evidence for asymmetric obligate dimers. Biochemistry Nov 7;39(44):13313-13323.
  • Suh JR, Oppenheim EW, Girgis S, Stover PJ (2000) Purification and properties of a folate-catabolizing enzyme. J Biol Chem Nov 10;275(45):35646-35655.
  • Oppenheim E, Stover PJ (2000) Mimosine's Action is pyridoxal-phosphate independent. Biochemistry and Molecular Biology of Vitamin B6 and PQQ-dependent Proteins. (Iriarte A, Kagan HM, Martinez-Carrion M., eds.). Birkhauser: Boston, Berlin.
  • Girgis S, Nasrallah IM, Suh JR, Oppenheim E, Zanetti KA, Mastri MG, Stover PJ (1998) Molecular cloning, characterization and alternative splicing of the human cytoplasmic serine hydroxymethyltransferase gene. Gene Apr 14;210(2):315-324.