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Liming Pei, Ph.D.

Liming Pei, Ph.D.

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Assistant Professor of Pathology and Laboratory Medicine
Department: Pathology and Laboratory Medicine
Graduate Group Affiliations

Contact information
CTRB 6018
3501 Civic Center Blvd.
Philadelphia, PA 19104
Office: 267-425-2118
Fax: 267-426-0978
Lab: 267-425-2145
Education:
B.S.
University of Science and Technology of China, 2000.
Ph.D.
UCLA, 2006.
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Description of Research Expertise

Metabolic regulation, mitochondrial function and human disease

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 favors fat as fuel source? Why do stem cells and many tumors prefer glycolysis while many 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 derangement 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.

We are currently working on the following research projects. We are also exploring other new ideas and we welcome students and fellows to join us in these efforts.

1.Cardiac metabolism and heart disease

We recently demonstrated that nuclear receptors ERRα and ERRγ together are essential transcriptional regulators of cardiac metabolism (fatty acid oxidation, mitochondrial OxPhos, etc) and function (contraction, conduction, etc) (Wang et al 2015 MCB). We are following up on studying the contributions of dysfunctional mitochondrial dynamics to heart disease, and the impact of pediatric heart disease on whole body metabolic status and health.

2.Mitochondrial function and mitochondrial disease

Mitochondria generate most of the energy of the cell and partial defects in mitochondrial function can cause an array of clinical symptoms. Mitochondrial dysfunction is also implicated in aging, obesity, diabetes and neurodegeneration. Mitochondrial disease affects hundreds of thousands people in the US. Currently there is no effective treatment and novel therapies are urgently needed. We are currently investigating the potential benefit of activated ERRα/ERRγ signaling in mitochondrial disease especially mitochondrial cardiomyopathy.

3. Mitochondrial function, neuronal metabolism and neurodegenerative diseases

The brain accounts for only about 2% of our body weight, but it consumes about 20-25% of the body's energy. Mature neurons almost exclusively use glucose as fuel and depend on mitochondrial OxPhos to generate energy essential for their survival and function. However, little is understood regarding the metabolic properties of different neuron populations. Using genomic methods (ChIP-Seq and RNA-Seq) and mice lacking ERRγ in specific neuronal population of the brain, we have recently demonstrated that ERRγ is a crucial transcriptional regulator of hippocampal neuronal metabolism and learning and memory (Pei et al 2015 Cell Metabolism). We are currently using different genetic mouse models to determine the physiological importance of ERRγ-dependent neuronal metabolism in different neuronal populations, with a focus on those that are critical for regulating whole body energy homeostasis and those related to neurodegenerative disease.

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-R., Downes, M., Yu, R., Powell, H.C., Lingrel, J.B., Evans, R.M.: Thyroid hormone receptor repression is linked to type I pneumocyte associated respiratory distress syndrome. Nat Med 17(11): 1466-1472, 2011.

Pei, L., and Evans, R.M: Retrofitting fat metabolism. Cell Metab 9(6): 483-484, 2009.

Pei, L., Waki, H., Vaitheesvaran, B., Wilpitz, D. C., Kurland, I. J., and Tontonoz, P: NR4A orphan nuclear receptors are transcriptional regulators of hepatic glucose metabolism. Nat Med 12(9): 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(4): 786-794, 2006.

Pei, L., Castrillo, A., Chen, M., Hoffmann, A., Tontonoz, P.: Induction of NR4A Orphan Nuclear Receptor Expression in Macrophages in Response to Inflammatory Stimuli. J Biol Chem 280(32): 29256-29262, 2005.

Pei, L., Tontonoz, P.: Fat's loss is bone's gain. J Clin Invest 113(6): 805-6, 2004.

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Last updated: 08/30/2016
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