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Methionine is an essential amino acid that is a key ingredient for the construction of proteins and other important biological molecules (Figure: Methionine Metabolic Pathway). The overall interest of my laboratory is how alterations in the methionine metabolic pathways contribute to human disease. Mutations and polymorphisms in methionine metabolic genes have been implicated in a variety of human diseases, ranging from rare inborn errors of metabolism to common diseases such as cardiovascular disease and cancer. Currently there are three major projects in the lab. Two concern particular methionine metabolic genes, cystathionine beta-synthase (CBS) and methylthioadenosine phosphorylase (MTAP). The third project is new and involves using methionine restriction in combination with COX-2 inhibitors for chemoprevention of breast cancer.

1. Gupta S, Kühnisch J, Mustafa A, Lhotak S, Schlacterman A, Slifker MJ, Klein-Szanto AJ, High KA, Austin RC, Kruger WD. Mouse models of cystathionine β-synthase deficiency reveal significant threshold effects of hyperhomocysteinemia. FASEB J. Forthcoming 2009. PubMed
2. Singh LR, Kruger WD. Functional rescue of mutant human cystathionine β synthase by manipulation of Hsp26 and Hsp70 levels in Saccharomyces cerevisiae. J Biol Chem. 2009;284:4238-45. PubMed
3. Mustafa A, Kruger WD. Suppression of tumor formation by a cyclooxygenase-2 inhibitor and a peroxisome proliferator-activated receptor γ agonist in an in vivo mouse model of spontaneous breast cancer. Clin Cancer Res. 2008;14:4935-42. PubMed
4. Gupta S, Wang L, Hua X, Krijt J, Kozich V, Kruger WD. Cystathionine β-synthase p.S466L mutation causes hyperhomocysteinemia in mice. Hum Mutat. 2008;29:1048-54. PubMed
5. Singh LR, Chen X, Kozich V, Kruger WD. Chemical chaperone rescue of mutant cystathionine β-synthase. Mol Genet Metabol. 2007;91:335-342. PubMed