Research Interests
Orphan Nuclear receptor, bile acid metabolism, atherosclerosis, lipid disorder, diabetes and colon cancer
Research in my laboratory focuses on elucidating the role of an “adopted” orphan nuclear receptor, farnesoid X receptor (FXR), on human diseases, such as arthrosclerosis, colon cancer, and metabolic syndrome. Nuclear receptors are ligand-activated transcription factors that are involved in various physiological, developmental, and toxicological processes. Using synthetic modulators to modify nuclear receptor activity provides a novel therapeutic strategy to treat human diseases with dysfunction of these receptors.
The nuclear receptors have highly conserved DNA- and ligand-binding domains, and are classified into several groups, based mainly upon their dimerization and ligand properties. FXR is essential in preventing the toxicity of bile acids, and is critical in maintaining the homeostasis of cholesterol and triglycerides. FXR regulates the expression of its target genes by feedback and feed-forward mechanisms. One of my current research interests focuses on how FXR deficiency affects hepatic and macrophage lipid metabolism, as well as on the role of FXR in colorectal cancer formation. To achieve these goals, we use in vivo and in vitro experimental models, including knockout and transgenic mice and human cell lines. Our laboratory uses a variety of cellular and molecular techniques, and has a wide collaboration with other laboratories.
Guo GL, Rose D, Flick JT, Barnett JB and Soderberg LSF: Acute exposure to the abused inhalant, isobutyl nitrite, reduced T cell responsiveness and spleen cellularity. Toxicology Letters, 116:151-158, 2000.
Guo GL and Klaassen CD: Protein-Kinase C suppresses rat organic anion transporting polypeptide 1- and 2-mediated uptake. J Pharmacol Exp Ther, 299: 551-557, 2001.
Guo GL, Johnson DR and Klaassen CD: Expression and induction by pregnenolone-16α-carbonitrile (PCN) of rat organic anion transporting polypeptide 2 (oatp2) in the liver during postnatal development, Drug Metab Dispos, 30:283-288, 2002.
Guo GL, Choudhuri S, and Klaassen CD: Induction profile of rat organic anion transporting polypeptide 2 (oatp2) by prototypical microsomal enzyme inducers that act through ligands-activated transcription factor pathways. J Pharmacol Exp Ther, 300:206-212, 2002.
Guo GL, Staudinger J, Ogura K and Klaassen CD: Induction of the rat organic anion transporting polypeptide 2 by pregnenolone-16α-carbonitrile is via Interaction with the pregnane-X-receptor. Mol Pharmacol, 61:832-839, 2002.
Johnson D, Guo GL, Klaassen CD: Expression of rat multidrug resistance protein 2 (Mrp2) in male and female rats during normal and pregnenolone-16α-carbonitrile (PCN)-induced postnatal ontogeny. Toxicology, 178:209, 2002.
Lambert G, Amar MJ, Guo GL, Brewer HB Jr, Gonzalez FJ, Sinal CJ: The farnesoid X-receptor is an essential regulator of cholesterol homeostasis. J Biol Chem 278:2563-70, 2003
Kitada H, Miyata M, Nakamura T, Tozawa A, Honma W, Shimada M, Nagata K, Sinal CJ, Guo GL, Gonzalez FJ, Yamazoe Y: Protective role of hydroxysteroid sulfotransferase in lithocholic acid-induced liver toxicity. J Biol Chem. 278:17838-44, 2003.
Wagner M, Fickert P, Zollner G, Fuchsbichler A, Silbert D, Tsybrovskyy O, Zatloukal K, Guo GL, Schuetz JD, Gonzalez FJ, Marschall HU, Denk H, Trauner M: Role of farnesoid X receptor in determining hepatic ABC transporter expression and liver injury in bile duct-ligated mice. Gastroenterology. 125: 825-838, 2003.
Guo GL, Lambert G, Negishi M, Ward J, Brewer HB Jr, Kliewer SA, Gonzalez FUJI, Sinal CJ: Complementary roles of farnesoid X receptor, pregnane X receptor, and constitutive androstane receptor in protection against bile acid toxicity. J Biol Chem. 278:45062-45071, 2003.
Guo GL, Moffit JS, Nicol CJ, Ward JM, Aleksunes LA, Slitt AL, Kliewer SA, Manautou JE, Gonzalez FJ: Enhanced acetaminophen toxicity by activation of the pregnane X receptor. Toxicol Sci. 82:374-80, 2004.
Grace L. Guo, Ph.D
.Assistant Professor
Department of Pharmacology, Toxicology and Therapeutics
The University of Kansas Medical Center
MS1018
3901 Rainbow Boulevard
Kansas City, KS 66160
Phone: (913) 588-0481
Fax: (913) 588-7501
E-Mail: lguo@kumc.edu
Updated 11/29/05
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The University of Kansas Medical Center