West Virginia University Health Science Center
United States of America
Works as Professor in Biochemistry.
Coenzyme A (CoA) is an essential and universally distributed cofactor that acts as the major acyl group carrier in the cell. Free CoA and acyl-CoAs are involved in hundreds of metabolic reactions, and are among a selected number of small molecules that have the ability to act as global regulators of cellular metabolism. Consistent with this key function, CoA levels are at the same time tightly regulated and flexible, so that the available supply is sufficiently adaptive to metabolic challenges such as fasting or a high fat diet. Regulation of CoA levels occurs through coordination of synthesis and degradation. In the liver, modulation of the amount of CoA contributes to the metabolic flexibility of this organ and to its ability to maintain glucose homeostasis during a fast. Conversely, in diabetic mice, hepatic CoA levels are abnormally high and unresponsive to changes in the nutritional state. Not much is known about CoA degradation. The goal of our research is to establish the importance of two recently discovered CoA-degrading enzymes, Nudt7 and Nudt19, in the regulation of CoA levels and glucose homeostasis. In particular, we are interested in studying these enzymes in the context of diabetes and other metabolic diseases using a combination of biochemistry, animal studies and metabolomics.
Sharma, L. K., Leonardi, R., Lin, W., Boyd, V. A., Goktug, A., Shelat, A. A., Chen, T., Jackowski, S., and Rock, C. O. (2015) "A high-throughput screen reveals new small-molecule activators and inhibitors of pantothenate kinases", J. Med. Chem. 58, 1563-1568
Shumar, S. A., Fagone, P., Alfonso-Pecchio, A., Gray, J. T., Rehg, J. E., Jackowski, S. and Leonardi, R. (2015) "Induction of Neuron-Specific Degradation of Coenzyme A Models Pantothenate Kinase-Associated Neurodegeneration by Reducing Motor Coordination in Mice", PLoS One. 2015 Jun 8;10(6):e0130013
Corbin, D.R., Rehg, J.E., Shepherd D.L., Stoilov, P., Percifield, R.J., Horner, L., Frase, S., Zhang, Y.M., Rock, C.O., Hollander, J.M., Jackowski, S. and Leonardi, R. (2017) "Excess coenzyme A reduces skeletal muscle performance and strength in mice overexpressing human PANK2" Mol. Genet. Metab. 120, 350-362