Charles A. Harris, M.D., Ph.D.

Assistant Professor
Internal Medicine
Endocrinology/Metabolism and Lipid Research

Molecular Cell Biology Program
Biochemistry, Biophysics, and Structural Biology Program
Molecular Genetics and Genomics Program
Developmental, Regenerative and Stem Cell Biology Program

  • 314-362-2967

  • 314-362-3802

  • 314-362-7641

  • 8127

  • Soutwest Tower 821

  • HARRISC@WUSTL.EDU

  • http://endo.wustl.edu/harris-lab/

  • stress, diabetes, obesity, steroids, CRISPR, glucocorticoids, nuclear hormone receptors, adipogenesis, adipocyte, fat

  • We aim to understand the molecular mechanisms underlying metabolic effects of glucocorticoids.

Research Abstract:

We are interested in the molecular mechanisms of glucocorticoid action. Glucocorticoids are stress hormones produced by the adrenal gland but are also used as medication to treat a wide variety of common inflammatory conditions such as asthma, inflammatory bowel disease and rheumatoid arthritis. Although glucocorticoids are potent and effective treatments for these conditions their use is limited due to severe side effects such as weight gain, diabetes/insulin resistance, hypertension, osteoporosis, myopathy as well as cognitive changes, a constellation of symptoms known as Cushing’s syndrome. We therefore hope to understand the site of action of glucocorticoids in manifesting these adverse effects. Central to this aim is a greater understanding of the glucocorticoid receptor, a member of the nuclear hormone receptor gene family. We currently use a spectrum of techniques from whole mouse physiology to cell biology to molecular biology. For our mouse studies, we use mice with quantitative alterations to both glucocorticoid ligand production (A Cushingoid transgenic mouse: the CRH-Tg mice or adrenalectomized mice) as well as GR signaling (whole knockout as well as tissue specific knockouts of GR). We also use mice with qualitative differences in GR signaling introduced by homologous recombination. We use a combination of traditional methods to study metabolism as well as cutting edge technologies including stable isotope mass spectrometry of whole mice to determine metabolic flux. For our cell-based studies we use mouse embryonic fobroblasts and adipocytes derived from these fibroblasts. These cells have the advantage of being primary cells that can be generated from a wide variety of genetically modified mice and are tractable to shRNA studies as well. We use a combination of cell culture and tissues from animals to perform whole-genome molecular approaches such as microarray and Chip-Seq to better understand molecular mechanisms of glucocorticoid action in physiologically relevant cell types.

Because of the prominent role of glucocorticoids on triacylglycerol metabolism and adipocyte biology, additional projects in the lab are focused on the triacylglycerol synthesis pathway, adipogenesis and adipocyte biology. A new project is the characterization of novel adipocyte specific genes identified in one of our microarray experiments. We are beginning to study these genes and have constructed 2 knockout mice lines to facilitate discovery of gene function.

Selected Publications:

Bose S, Hutson, I, Harris C.Hepatic GR is more imprtant than adipose despite renal compensation. JBC 2016, in press.

Harris, C, Roohk DJ, Boudignon B, Halloran B, Hellerstein M Large increases in adipose triacylglycerol flux in Cushingoid CRH-Tg mice are explained by futile cycling. Am J Physiol Endocrinol Metab. 2013 304(3):E282-93. PMID: 23211515. PMCID: PMC3566431

Roohk DJ, Hellerstein, M, Harris C. Dexamethasone Mediated Changes in Adipose Triacylglycerol Metabolism Are Exacerbated in the Absence of a Functional GR Dimerization Domain. Endocrinology. 2013;154(4):1528-39. PMID:23493372. PMCID:PMC3602623

Kuo T, Harris C, Wang JC. Metabolic Functions of Glucocorticoid Receptor in Skeletal Muscle. Molecular and Cellular Endocrinology. 2013. Mol Cell Endocrinology S0303-7207(13)00088-9. PMID:23523565

Wang JC, Gray NE, Kuo T, Harris C. Regulation of Triglyceride Metabolism by Glucocorticoid Receptor. Cell Biosci. 2012 2(1):19. PMID:22640645. PMCID: PMC3419133

Kuo T, Lew MJ, Mayba O, Harris C, Speed TP, and JWang JC. Genome-Wide Analysis of Glucocorticoid
Receptor Binding Sites in Myotubes Identifies Gene Networks Modulating Insulin Signaling Pathway
Proc Natl Acad Sci U S A. 2012 109(28):11160-5. PMID: 22733784. PMCID: PMC3396543.

Yu CY, Mayba O, Lee JV, Tran J, Harris C, Speed T, and Wang JC. Genome-wide analysis of glucocorticoid receptor binding regions in adipocytes reveal gene network involved in triglyceride metabolism. PLoS ONE 5(12): e15188., 2010. PMID: 21187916. PMCID: PMC3004788


Last Updated: 9/9/2016 3:45:12 PM

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