Liming Pei, Ph.D.

faculty photo
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
University of Science and Technology of China, 2000.
UCLA, 2006.
Permanent link

Description of Research Expertise

Cardiac endocrinology, Metabolic regulation and metabolic disease, 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 endocrinology
We have recently identified GDF15 as a heart-derived hormone that regulates pediatric body growth (Wang et al 2017 EMBO Molecular Medicine). We show that pediatric heart disease induces GDF15 synthesis and secretion by cardiomyocytes. Circulating GDF15 in turn acts on the liver to inhibit growth hormone (GH) signaling and body growth. Our study reveals a new endocrine mechanism by which the heart coordinates cardiac function and body growth, and provided a potential mechanism for the well-established clinical observation that children with heart diseases often develop failure to thrive (FTT). In addition to further understand the biology and mechanism of action of GDF15, we are exploring the endocrine function of the heart (cardiac endocrinology) which was so far little understood or appreciated. We are combining single cell genomics, molecular and cell biology, and genetic models of human disease in this endeavor.

2. 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.

3. 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.

4. 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

Zhao J, Lupino K, Wilkins BJ, Qiu C, Liu J, Omura Y, Allred AL, McDonald C, Susztak K, Barish GD, Pei L: Genomic integration of ERRγ-HNF1β regulates renal bioenergetics and prevents chronic kidney disease. PNAS Epub ahead of print, May 2018.

Wang T, Liu J, McDonald, C, Lupino K, Zhai X, Wilkins BJ, Hakonarson H, Pei L : GDF15 is a heart-derived hormone that regulates body growth. EMBO Molecular Medicine 9: 1150-1164, 2017.

Pei L, Wallace DC : Mitochondrial Etiology of Neuropsychiatric Disorders. Biological Psychiatry 2017.

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

back to top
Last updated: 05/10/2018
The Trustees of the University of Pennsylvania