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Amino acids are the building blocks of proteins and other important biological molecules. The sulfur containing amino acid methionine is especially interesting as alterations in methionine metabolism and methionine-related pathways are found in many human diseases (Figure 1), including 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). A third project is related to understanding how alterations in amino acid metabolism contributes to renal cell carcinoma.

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. 2009 Mar;23(3):883-93. 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. Singh LR, Gupta S, Honig N, Kraus JP, Kruger WD. Activation of mutant enzyme function by proteasome inhibitors and treatments that induce Hsp70. PLOS Genetics Jan;6(1):e1000807, 2010.
5. Kadariya Y, Yin B, Tang BQ, Shinton SA, Quinlivan EP, Hua X, Klein-Szanto A, Al-Saleem TI, Bassing CH, Hardy RR, Kruger WD. Mice Heterozygous for Germ-line Mutations in Methylthioadenosine Phosphorylase (MTAP) Die Prematurely of T-Cell Lymphoma. Cancer Res. 2009 Jul;69(14):5961-9.