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 area of 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 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. 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.
This project is addressing the metabolic pathways underlying the association between erythritol exposure, endogenous erythritol synthesis, central metabolism, and weight/central adiposity gain.