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Assistant Professor of Pharmacology
Primary Office: 2-238 Bowen Science BuildingIowa City, IA 52242
Primary Office Phone: 319-384-4438
Lab: 2-200 Bowen Science BuildingIowa City, IA 52242
Email: firstname.lastname@example.orgWeb: http://www.medicine.uiowa.edu/pharmacology/
BS, Suma Cum Laude, Biology / Zoology, University of OklahomaPhD, Genetics and Development, University of Texas Southwestern Medical Center
Postdoctoral Fellow, Howard Hughes Medical Institute, University of Texas Southwestern Medical Center
Biosciences Graduate ProgramInterdisciplinary Graduate Program in GeneticsInterdisciplinary Graduate Program in Molecular and Cellular Biology
The regulation of metabolic homeostasis is a complex process coordinated by numerous growth factors and hormones signaling the availability of energy and nutrients. Organisms must properly perceive and respond to these signals to maintain homeostasis. The main goals of my lab are: 1) to identify secreted proteins and transcription factors that regulate nutritional status and contribute to metabolic disease, 2) to determine molecular mechanisms for these signals, 3) to understand how these pathways regulate biological functions, and 4) how dysregulation of these pathways contribute to metabolic disease (i.e., in diabetes and cancer). To accomplish these goals, my lab integrates biochemistry, proteomics, cell biology, metabolomics, and mouse genetics. We currently have multiple projects aimed at addressing these goals, with the two main projects focused on the endocrine fibroblast growth hormone 21 (FGF21) and a hepatic transcription factor termed Tox.
In mammals, the liver is important in maintaining whole body energy balance during feeding and fasting through regulation of carbohydrate and lipid metabolism. While hormones such as insulin and glucagon have long been known to control energy balance in response to nutritional status, additional metabolic hormones, including FGF21, have recently been shown to be important regulators of hepatic metabolism. FGF21 is an atypical FGF that lacks the conventional heparin-binding domain found in most other members of the FGF family. As a consequence, endocrine FGFs can circulate as hormones and signal through cell-surface receptors comprised of classical FGF receptors (FGFRs) complexed with beta-Klotho. Our previous work has demonstrated that FGF21 is sufficient to drive the hepatic fasting response by rapidly inducing hepatic expression of peroxisome proliferator-activated receptor gamma coactivator protein-1alpha (PGC-1alpha), a key transcriptional regulator of energy homeostasis (Potthoff et al. 2009). More recently, FGF21 was shown to act on white and brown adipose tissue, and these actions of FGF21 likely represent an extension of its role in the adaptive starvation response. In contrast to the physiological actions of FGF21 in lean animals, pharmacological studies have shown that FGF21 administration markedly improves insulin sensitivity, lowers lipid levels, and reduces body weight in obese animal models. Thus, FGF21 remarkably improves a number of metabolic parameters in obese rodents. The mechanism by which endocrine FGFs perform these remarkable pharmacologic effects on carbohydrate and lipid metabolism is largely unknown and is currently an area of interest of the lab.
A second line of investigation in the lab is how Tox, a transcription factor, regulates hepatic lipid and glucose metabolism in vivo. Using genetically engineered Tox total and liver-specific conditional KO mice, as well as mice with acute liver-specific overexpression of Tox via adenovirus injection, we will elucidate the function of Tox during fasting and obesity. Our recent findings suggest that Tox is an important regulator of hepatic lipid and glucose metabolism during both of these conditions. The precise mechanism of Tox action is unclear, but we are currently using multiple techniques to identify Tox target genes in the liver and the mechanism by which it regulates carbohydrate and lipid metabolism in vivo. By identifying and studying pathways which signal energy and nutrient availability, we hope to gain insight into metabolic dysfunction and find novel candidates for the treatment of metabolic disease.
Center for Gene Therapy of Cystic Fibrosis and other Genetic DiseasesFraternal Order of Eagles Diabetes Research Center
Colesevelam Suppresses Hepatic Glycogenolysis by TGR5-mediated Induction of GLP-1 Action in DIO Mice.
Am J Physiol: Gastrointestinal and Liver Physiol.
2013 February. 304(4):G371-G380.
The starvation hormone, fibroblast growth factor-21, extends lifespan in mice.
2012 October 15. 1:e00065.
Endocrine fibroblast growth factors 15/19 and 21: from feast to famine.
2012 February 15. 26(4):312-324.
FGF15/19 regulates hepatic glucose metabolism by inhibiting the CREB-PGC-1α pathway.
2011 June 8. 13(6):729-738.
Myogenin and class II HDACs control neurogenic muscle atrophy by inducing E3 ubiquitin ligases.
2010 October 1. 143(1):35-45.
Progressive adaptation of hepatic ketogenesis in mice fed a high-fat diet.
Am J Physiol Endocrinol Metab.
2010 June. 298(6):E1226-E1235.
FGF21 induces PGC-1alpha and regulates carbohydrate and fatty acid metabolism during the adaptive starvation response.
Proc Natl Acad Sci U S A.
2009 June 30. 106(26):10853-10858.
Maintenance of cardiac energy metabolism by histone deacetylase 3 in mice.
J Clin Invest.
2008 November. 118(11):3588-3597.
MEF2: a central regulator of diverse developmental programs.
2007 December. 134(23):4131-4140.
Regulation of skeletal muscle sarcomere integrity and postnatal muscle function by Mef2c.
Mol Cell Biol.
2007 December. 27(23):8143-8151.
Date Last Modified: 09/04/2013 -
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