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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 cytosolic 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. 

Selected Publications:

  • Misselbeck, K., Marchetti, L., Priami, C.,  Stover, P.J., and Field, M.S. (2018) An extended hybrid-stochastic model of folate-mediated one-carbon metabolism: 5-formyltetrahydrofolate futile cycle regulates de novo purine synthesis and reduces pathway stochasticity.  Sci Rep., In press.
  • Garza, C., Stover, P.J., Ohlhorst, S.D., Field, M.S., Steinbrook, R., Rowe, S., Woteki, C., and Campbell, E., (2019)  Best practices in nutrition science to earn and keep the public’s trust.  Amer. J. Clin. Nutr., 0:  1-19.
  • Alonzo, J.R., Venkataraman, C., Field, M.S., and Stover, P.J.  (2018) The mitochondrial inner membrane protein MPV17 prevents uracil accumulation in mitochondrial DNA.  J. Biol. Chem., 293:  20285-20294.
  • Lan, X., Field, M.S., and Stover, P.J. (2018) Cell Cycle Regulation of Folate-Mediated One-Carbon Metabolism.  Wiley Interdisciplinary Reviews: Systems Biology and Medicine, 10:e1426.
  • Field, M.S., Kamynina, E., Chon, J., and Stover, P.J. (2018) Nuclear Folate Metabolism.  Ann. Rev. Nutr., 38:  219-43.
  • Field, M.S., Lan, X., Stover, D.M., and Stover, P.J. (2018) Uridine modifies tumorigenesis in the ApcMin/+ model of intestinal cancer.  Curr. Dev. Nutr., 2:  nzy013
  • Field, M.S. and Stover, P.J. (2017) Safety of folic acid.  Ann. NY Acad. Sci., 1414:  59-71.
  • Stover, P.J., Durga, J., and Field, M.S. (2017) Folate and blood-brain barrier dysfunction.  Curr. Opin. Biotechnol., 44:  146-152.
  • 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.  Proc. Natl. Acad. Sci., 114:  E4095-4102 
  • Kamynina, E., Lachenauer, E., DiRisio, A.C., Liebenthal, R.P., Field, M.S., and Stover, P.J. (2017) Arsenic trioxide targets MTHFD1 and SUMO-dependent nuclear de novo thymidylate biosynthesis.  Proc. Natl. Acad. Sci., 114:  E2319-E2326.
  • Misselbeck, K., Marchetti, L., Field, M.S., Scotti, M., 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.
  • Bae, S., Chon, J., Field, M.S., and Stover, P.J. (2017) Alcohol dehydrogenase 5 is a source of formate for de novo purine biosynthesis in HepG2 cells.  J. Nutr., 147:  499-505.
  • Chon, J., Stover, P.J., and Field, M.S. (2017) Targeting Nuclear Thymidylate Biosynthesis.  Molecular Aspects of Medicine, 53:  48-56.
  • Stover, P.J., Berry, R.J., and Field, M.S. (2016) Time to think about nutrient needs in chronic disease.  JAMA Internal Medicine, 176:  1451-1452
  • Field, M.S., Stover, P.J., and Kisliuk, R. (2016) Thymidylate Synthesis.  In: eLS. John Wiley & Sons, Ltd: Chichester. DOI: 10.1002/9780470015902.a0001397.pub3
  • Field, M.S., Kamynina E., Watkins, D., Rosenblatt, D.S., Stover, P.J. (2016) MTHFD1 regulates nuclear de novo thymidylate biosynthesis and genome stability.  Biochimie, 126: 27-30.
  • 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.  Rare Diseases, 3: 1, e1112479.

I served as a member of the writing group for a committee from the American Society for Nutrition (ASN) in producing 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 was recently published in the American Journal of Clinical Nutrition.  In addition, I am currently a member of ASN's Committee on Advocacy and Science Policy.

 

 

 

 

I am currently the instructor for NS3320, “Methods in Nutritional Sciences,” a required course for Nutritional Sciences majors. 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 also supervise undergraduate students in independent research courses including NS4010, and BIO2990.  

 

 

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.

Twitter:  @marthafield7