|Current Research Activities:|
Folate-dependent one-carbon metabolism is required for the synthesis of purines, thymidylate, and methionine. Alterations in folate metabolism can result from folate deficiency, polymorphisms in genes that encode folate-dependent enzymes, increased rates of folate degradation, and/or other B-vitamin deficiencies. Pertrubations in this network are associated with adverse physiological outcomes that include certain cancers, cardiovascular disease, and neural tube defects. De novo synthesis of thymidylate (dTMP) within the nucleus, and the misincorporation of uracil within DNA that results from insufficient dTMP synthesis, has become a focus of work in the lab.
Similarly, the recent identification of a distinct mitochondrial de novo thymidylate synthesis pathway involving SHMT2 and DHFRL1 (isozymes of SHMT1 and DHFR), we have begun to investigate the effects of perturbed one-carbon metabolism on mitochdrial DNA content and integrity using a number of cell culture model systems. We are developing assays and model systems to determine where uracil is misincorporated into DNA and what the consequences and potential modifiers of this accumulation are.
Field, M.S., et. al. (2013) Reduced MTHFD1 activity in male mice perturbs folate- and choline-dependent one-carbon metabolism as well as transsulfuration. J. Nutr. 143: 1-5.
Field, M.S., Anderson, D.D., and Stover, P.J. (2011) Mthfs is an essential gene in mice and a component of the purinosome. Front. Gene. 2: 1-13.
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. Arch. Biochem. Biophys. 481: 145-150.
Field, M.S., Young, M.F., and O’Brien, K.O. “Maternal iron status and transfer of iron to the fetus.” Physiology of Mother-Fetus Relationship. (2009) Ed. Lafond, J., and Vaillancourt, C. Kerala: Research Signpost.
Field, M.S., Szebenyi, D.M.E., and Stover, P.J. (2006) Regulation of de novo purine biosynthesis by methenyltetrahydrofolate synthetase in neuroblastoma. J. Biol. Chem. 281: 4215-4222.
Field, M.S., Szebenyi, D.M.E., Perry, C.A., and Stover P.J. (2007) Inhibition of 5,10-methenyltetrahydrofolate synthetase. Arch. Biochem. Biophys. 458: 194-201.
Field, M.S. and Stover, P.J. (2007) Regulation of the 5-formyltetrahydrofolate futile cycle and purine biosynthesis by methenyltetrahydrofolate synthetase in The Proceedings of the 13th International Symposium on Chemistry and Biology of Pteridines and Folates.
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. Biol. Chem. 281: 18335-18342.