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Martha

Field

Assistant Professor
113 Savage Hall
Ithaca, New York
Division of Nutritional Sciences

Biography

I am an Assistant Professor in the Division of Nutritional Sciences at Cornell University. I received a B.S. in chemistry from Butler University in 2000 and a Ph.D. in Biochemistry, Molecular and Cell Biology from Cornell University in 2007. 

My research has used several in vitro and in vivo model systems to study the mechanisms that underlie physiological outcomes associated with perturbed one-carbon metabolism. More specifically, inadequate thymidylate (dTMP, or the “T” base in DNA) can result in misincorporation of uracil into DNA, which then leads to DNA damage and genome instability in both nuclear and mitochondrial DNA. Recent studies using isotope tracer methodologies have elucidated mechanisms whereby mammalian cells respond to folate deficiency to spare nuclear dTMP synthesis at the expense of methionine synthesis. We have also shown that nucleotide precursors of thymidylate, namely uridine and deoxyuridine, have distinct fates in DNA, and dietary intake of each of these nucleosides uniquely modifies folate-responsive birth defects and colon tumor formation in mice. 

Currently, my laboratory studies gene-nutrient-environment interactions that lead to development of pathology.  Mitochondrial de novo dTMP biosynthesis is considerably more sensitive to folate depletion than nuclear de novo dTMP synthesis, as measured by misincorporation of uracil into mitochondrial DNA.  Elucidating the molecular mechanisms linking folate nutrition and enzyme expression/localization in supporting mitochondrial de novo dTMP synthesis is also a focus of my current research--especially as related to mitochondrial DNA integrity and pathogenesis of metabolic diseases such as mitochondrial DNA depletion syndromes, chronic disease, and age-related decline in mitochondrial function. 

We have also recently identified two enzymes responsible for synthesis of erythritol from the pentose phosphate pathway.  Erythritol, a four-carbon sugar alcohol, was recently shown to be a biomarker of central adiposity gain in young adults.  This project is addressing the metabolic pathways underlying the association between erythritol exposure, endogenous erythritol synthesis, central metabolism, and weight/central adiposity gain. 

 

 

My research interest is folate-dependent one-carbon metabolism, which is required for synthesis of DNA precursors and methionine. Perturbations in this network may result from folate deficiency, polymorphisms in genes that encode folate-dependent enzymes, and/or other B-vitamin deficiencies. These perturbations are associated with adverse physiological outcomes that include certain cancers, cardiovascular disease, neurological impairments, and birth defects. While fortification of the food supply with folic acid has decreased birth defect rates both in the U.S. and throughout the world, the mechanisms that underlie this response and possible interactions with other clinical outcomes are not completely understood.

My research uses several in vitro and in vivo model systems to study the mechanisms that underlie physiological outcomes associated with perturbed one-carbon metabolism. More specifically, inadequate thymidylate (dTMP, or the “T” base in DNA) can result in misincorporation of uracil into DNA, which then leads to DNA damage and genome instability. Recent studies using isotope tracer methodologies have elucidated mechanisms whereby mammalian cells respond to folate deficiency to spare nuclear dTMP synthesis at the expense of methionine synthesis. We have also shown that nucleotide precursors of thymidylate, namely uridine and deoxyuridine, have distinct fates in DNA, and dietary intake of each of these nucleosides uniquely modifies folate-responsive birth defects and colon tumor formation in mice. My current and future research will extend these studies to understand the mechanisms by which perturbed one-carbon metabolism and genome instability affect pathologies including peripheral neuropathy, neurological disorders, and lung cancer.

 

Mitochondrial de novo dTMP biosynthesis is considerably more sensitive to folate depletion than nuclear de novo dTMP synthesis, as measured by misincorporation of uracil into mitochondrial.  Elucidating the molecular mechanisms linking folate nutrition and enzyme expression/localization in supporting mitochondrial de novo dTMP synthesis is also a focus of my current research--especially as related to mitochondrial DNA integrity and pathogenesis of metabolic diseases such as mitochondrial DNA depletion syndromes, chronic disease, and age-related decline in mitochondrial function. 

 

 A new project is to investigate the metabolic pathways underlying the association between erythritol exposure, endogenous erythritol synthesis, central metabolism, and weight/central adiposity gain. 

Journal Article Refereed

Field, M.S. and Stover, P.J. (2017) Safety of folic acid.

Ann. NY Acad. Sci., Epub ahead of print Proc. Natl. Acad. Sci., 114: E4095-4102 de novo thymidylate biosynthesis. Proc. Natl. Acad. Sci., 114: E2319-E2326. 4, Priami, C., and Stover, P.J. (2017) A hybrid stochastic model of folate-mediated one-carbon metabolism: Effect of the common C677T MTHFR variant on de novo thymidylate biosynthesis. Sci Rep., 11: 797. de novo purine biosynthesis in HepG2 cells. J. Nutr., 147: 499-505. Molecular Aspects of Medicine, 53: 48-56. . JAMA Internal Medicine, 176: 1451-1452

Palmer, A.M., Kamynina, E., Field, M.S., and Stover, P.J. (2017) Folate rescues vitamin B12 depletion-induced inhibition of nuclear thymidylate biosynthesis and genome instability.

Kamynina, E., Lachenauer, E., DiRisio, A.C., Liebenthal, R.P., Martha S. Field, M.S., and Stover, P.J. (2017) Arsenic trioxide targets MTHFD1 and SUMO-dependent nuclear

Misselbeck, K., Marchetti, L., Field, M.S., Scotti, M.

Bae, S., Chon, J., Field, M.S., and Stover, P.J. (2017) Alcohol dehydrogenase 5 is a source of formate for

Chon, J., Stover, P.J., and Field, M.S. (2017) Targeting Nuclear Thymidylate Biosynthesis.

Stover, P.J., Berry, R.J., and Field, M.S. (2016) Time to think about nutrient needs in chronic disease

Rare Diseases, 3: 1, e1112479.

 

Stover, P.J., MacFarlane, A.J., and Field, M.S. (2015) Bringing clarity to the role of MTHFR variants in neural tube defect prevention.

Martiniova, L, Field, M.S., Finkelstein, J.L., Perry, C.A. and Stover, P.J. (2015) Maternal dietary uridine causes, and deoxyuridine prevents, neural tube closure defects in a mouse model of folate-responsive neural tube defects.

Field, M .S., Kamynina E., Watkins, D., Rosenblatt, D.S., Stover, P.J. (2015) Human Mutations in Methylenetetrahydrofolate Dehydrogenase 1 Impair Nuclear

Field, M .S., Kamynina E., Agunloye, O.C., Liebenthal, R.P., Lamarre, S.G.,Brosnan, M.E., Brosnan, J.T., and Stover, P.J. (2014) Nuclear enrichment of folate cofactors and methylenetetrahydrofolate dehydrogenase 1 (MTHFD1) protect de novo thymidylate biosynthesis during folate deficiency.

Am. J. Clin. Nutr., 101: 111-2. Am. J. Clin. Nutr., 101: 860-9. de novo Thymidylate Biosynthesis. Proc. Natl. Acad. Sci., 112: 400-405.

 

Field, M.S., Shields, K.S., Abarinov, E.V., Malysheva, O.V., Allen, R.H., Stabler, S.P., Ash, J.A., Strupp, B.J., Stover, P.J., and Caudill, M.A. (2013) Reduced MTHFD1 activity in male mice perturbs folate- and choline-dependent one-carbon metabolism as well as transsulfuration.

Abarinov. E.V., Beaudin, A.E., Field, M.S., Perry, C.A., Allen, R.H., Stabler, S.P. and Stover, P.J. (2013) Disruption of

Stover, P.J. and Field, M.S. (2011) Trafficking of Intracellular Folates.

Field, M.S., Anderson, D.D., and Stover, P.J. (2011)

Field, M.S., Anguera, M.C., Page R., and Stover, P.J. (2009) 5,10-Methenyltetrahydrofolate synthase activity is increased in tumors and modified the efficacy of antipurine LY309887.

 

Field, M.S., Szebenyi, D.M.E., and Stover, P.J. (2006) Regulation of de novo purine biosynthesis by methenyltetrahydrofolate synthetase in neuroblastoma.

Field, M.S., Szebenyi, D.M.E., Perry, C.A., and Stover P.J. (2007) Inhibition of 5,10-methenyltetrahydrofolate synthetase.

 

Anguera, M.C., Field, M.S., Perry, C., Ghandour, H., Chiang, E.P., Selhub J., Shane, B., and Stover, P.J. (2006) Regulation of folate-mediated one-carbon metabolism by 10-formyltetrahydrofolate dehydrogenase.

J. Nutr. 143: 1-5. Shmt1 impairs hippocampal neurogensis and mnemonic function in mice (2013) J. Nutr. 143: 1028-35. Adv. Nutr. 2: 325-31. Mthfs is an essential gene in mice and a component of the purinosome. Front. Gene. 2: 1-13. Arch. Biochem. Biophys. 481: 145-50. J. Biol. Chem. 281: 4215-22. Arch. Biochem. Biophys. 458: 194-201. J. Biol. Chem. 281: 18335-18342.

 

Field, M.S., Kamynina E., Watkins, D., Rosenblatt, D.S., Stover, P.J. (2015) New insights into the metabolic and nutritional determinants of severe combined immunodeficiency.

Current professional activities include co-direction of the laboratory of Dr. Patrick Stover, including the supervision and training of undergraduate and graduate students.  My primary objectives are to 1) assist undergraduate and graduate students with experimental design and execution and 2) maintain and integrate the flow of experimental practice and knowledge between lab members. 

I am currently working with a committee from the American Society of Nutrition to write a report on best practices to facilitate collaboration between academia, industry, and government that ensures rigorous research conduct and transparency between all parties and the public.   This report should be published in early 2018.

 

 

 

 

I am currently the lecturer for NS3320, “Methods in Nutritional Sciences,” a required course for Nutritional Sciences majors at Cornell University. This laboratory-based course introduces students to the principles and analytical techniques used in nutritional sciences and aims to help students develop skills in data analysis, data interpretation, and scientific writing in addition to mastering basic laboratory techniques that are most relevant to nutrition.  I try to meet these goals by introducing laboratory concepts in lecture before the students attend lab sections, being present during lab sections, and during in-class "workshops" on data analysis and presentation.  Because so many of the students plan careers in health care, one goal of NS3320 is to further understanding of how to find, evaluate, use, and communicate what is in the scientific literature.

I also supervise undergraduate students in independent research courses including NS4010, and BIO2990.  My goal with undergraduate research students is to perform experiments with them when necessary, but also to enable them to become independent both in terms of execution of experiments and in asking relevant questions and planning future experiments.

I currently advise about twenty undergraduates in the Nutritional Sciences and HBHS majors in the College of Human Ecology.  I meet with my advisees on an "as needed" basis and interact with most of them in-person at least one time per semester in addition to communicating via email.

I also currently serve as co-chair of one graduate student's special committee. 

 

NS3320, Methods in Nutritional Sciences

NS4010, Empirical Research (Independent undergraduate research)

BIOG2990, BIOG4990 (Independent undergraduate research)

2007:  PhD in Biochemistry, Cell and Molecular Biology, Cornell University, Ithaca, NY.
2000:  BS in Chemistry, Butler University, Indianapolis, IN.

I currently serve as the department safety representative (DSR) for the Division of Nutritional Sciences.