Research Statement

Metabolic dysregulation has long been associated with many human diseases including heart disease, diabetes and obesity. Research in recent years has also linked disordered metabolism to cancer, stem cell function, development and almost every aspect of biology. However, how metabolism is regulated at the molecular, genomic, cellular and organismal levels is still poorly understood. Why do mature neurons use glucose exclusively while the adult heart prefers fat as fuel source? Why do stem cells and many tumors prefer glycolysis while most differentiated cells exploit oxidative phosphorylation? Can we apply our knowledge of metabolism to the management of medical conditions – such as neurodegenerative disorders – not traditionally conceptualized as derangements of metabolism?
We strive to answer these questions utilizing a variety of experimental approaches from molecular and cell biology to genetics and genomics.  The goal of our research is to understand metabolism and metabolic regulation in both normal physiology and disease states and apply this knowledge to human health and medicine.

Selected Publications

• Wang, T., McDonald, C., Petrenko, N.B., Leblanc, M., Giguere, V., Evans, R.M., Patel, V.V., and Pei, L.: ERRalpha and ERRgamma are essential coordinators of cardiac metabolism and function. Mol Cell Biol. 35(7): 1281-1298, 2015.
• Pei, L, Mu, Y., Leblanc, M., Alaynick, W., Barish, G.D., Pankratz, M., Tseng, T.W., Kaufman, S., Liddle, C., Yu, R.T., Downes, M., Pfaff, S.L., Auwerx, J., Gage, F.H., Evans, R.M.: Dependence of hippocampal function on ERRγ regulated mitochondrial metabolism. Cell Metab 21(4): 628-636, 2015.
• Pei, L, Leblanc M, Barish G, Atkins A, Nofsinger R, Whyte J, Gold D, He M, Kawamura K, Li H, Downes M, Yu RT, Powell HC, Lingrel JB, Evans RM. Thyroid hormone receptor repression is linked to type I pneumocyte associated respiratory distress syndrome. Nat Med 17, 1466-1472, 2011.
• Pei L, Waki H, Vaitheesvaran B, Wilpitz DC, Kurland IJ and Tontonoz P. NR4A orphan nuclear receptors are transcriptional regulators of hepatic glucose metabolism. Nat Med 12, 1048-1055, 2006.
• Pei L, Castrillo A and Tontonoz P.Regulation of macrophage inflammatory gene expression by the orphan nuclear receptor Nur77. Mol Endocrinol 20, 786-794, 2006.
• Pei L, Castrillo A, Chen M, Hoffmann A and Tontonoz P. Induction of NR4A Orphan Nuclear Receptor Expression in Macrophages in Response to Inflammatory Stimuli.  J Biol Chem 280, 29256-29262, 2005. 

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