Thomas Roche, Ph.D.
University Distinguished Professor Emeritus
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Areas of specialty
- Structure, function and regulation of mammalian pyruvate dehydrogenase complex
Dr. Thomas Roche is one of the world’s leading experts on the pyruvate dehydrogenase complex (PDC). He is highly cited for his biochemical analyses of the pyruvate dehydrogenase kinases (PDKs) and pyruvate dehydrogenase phosphatases (PDPs) that control the activity of the PDC. A long-standing focus of his research has been understanding the structure, molecular interactions and effector control of PDK and PDP isoforms. His work was facilitated by developing E. coli expression systems for producing most of the components of the PDC, including E1, E2, E3-E3BP, E3, four PDKs, and the catalytic subunit of PDP1. His discoveries may lead to new treatments for diabetes or cancer. Dr. Roche has continued to study PDC well past his official retirement date in 2012, with his most recent project requiring the addition of an evolutionary biology perspective to his ongoing biochemistry-based research strategies.
Selected publications
Guo, Y., Qiu, W., Roche, T.E., Hackert, M.L. (2020) Crystal structure of the catalytic subunit of bovine pyruvate dehydrogenase phosphatase. Acta Crystallogr. F Struct. Biol. Commun. 76, 292-301. With online Supplemental Information.
Jiang, J., Baiesc, F.L., Hiromasa, Y., Yu, X., Hui, W.H., Dai, X., Roche, T.E., Zhou, Z.H. (2018) Atomic Structure of the E2 Inner Core of Human Pyruvate Dehydrogenase Complex. Biochemistry 57, 2325-2334.
Hiromasa, Y., Yan, X., and Roche, T. E. (2008) Specific ion influences on self-association of pyruvate dehydrogenase kinase isoform 2 (PDHK2) binding of PDHK2 to the L2 lipoyl domain, and effects of the lipoyl group-binding site inhibitor, Nov3r. Biochemistry 47:2312-2324.
Hiromasa, Y. and Roche, T. E. (2008) Critical role of specific ions for ligand-induced changes regulating pyruvate dehydrogenase kinase isoform 2. Biochemistry 47:2298-2311.
Yu, X., Hiromasa, Y., Tsen, H., Chiu, W., Stoops, J. K., Roche, T. E., and Zhou, Z. H. (2008) Structures of the human pyruvate dehydrogenase complex cores: a highly conserved catalytic center with flexible N-terminal domains. Structure 16:104-114.
Roche, T. E. and Hiromasa, Y. (2007) Pyruvate dehydrogenase kinase regulatory mechanisms and inhibition in treating diabetes, heart ischemia, and cancer. Cell. and Mol. Life Sci. 64:830-849.
Knoechel, T. R., Tucker, A. D., Robinson, C. M., Phillips, C., Taylor, W., Bungay, P. J., Kasten, S. A., Roche, T. E., and Brown, D. G. (2006) Regulatory roles of the N-terminal domain based on crystal structures of human pyruvate dehydrogenase kinase 2 containing physiological and synthetic ligands. Biochemistry 45:402-415.
Hiromasa, Y., Hu, L., and Roche, T. E. (2006) Ligand-induced Effects on Pyruvate Dehydrogenase Kinase Isoform 2. J. Biol. Chem. 281:12568-12579.