Clavia Ruth Wooton-Kee, Ph.D.
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Positions
- Assistant Professor
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Pediatrics
Nutrition
Baylor College of Medicine
Houston, TX US
- Faculty Senator
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Baylor College of Medicine
Houston, Texas
- Assistant Professor
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Molecular and Cellular Biology - Secondary Appointment
Baylor College of Medicine
- Assistant Professor
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Pediatrics - Secondary Appointment
Gastroenterology, Hepatology, and Nutrition
Baylor College of Medicine
Addresses
- Children's Nutrition Research Center (CNRC) (Lab)
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1100 Bates
Office: 9070
Houston, TX 77030
United States
Phone: (713) 798-0372
wootenke@bcm.edu
Education
- BSc from Union College
- 05/1996 - Barbourville, Kentucky United States
- Biology and Chemistry
- MS from University of Louisville, School of Medicine
- 12/1999 - Louisville, Kentucky United States
- Biochemistry
- PhD from University of Kentucky, College of Medicine
- 12/2008 - Lexington, Kentucky United States
- Toxicology
Professional Statement
The overall goal of my research program is to understand the role of nuclear receptors in hepatic metabolism and chronic liver disease. Our previous and current studies have utilized a mouse model for Wilson’s disease (Atp7b-/- mouse). Wilson’s disease results from mutations in the Atp7b transporter, which leads to excessive hepatic copper levels and progressive liver disease. Wilson’s disease patients and Atp7b-/- mice have profound mitochondria and nuclear ultrastructural changes that are likely due to copper induction of redox stress in the hepatocyte. Atp7b-/- mice also develop spontaneous hepatic nodules between 10-16 months of age. Our lab identified that excessive copper concentrations decreased metabolic nuclear receptor activity (FXR - farnesoid X receptor, HNF4a – hepatocyte nuclear factor, and LRH-1 – liver receptor homolog-1) in vivo and in Atp7b-/- mice (Wooton-Kee, et. al, JCI, 2015). We also found that Atp7b-/- mice exhibited reduced adiposity and hepatic steatosis and were more insulin sensitive compared with wild-type mice (Wooton-Kee, et. al, PNAS, 2020).Our current projects aim to understand the mechanisms driving metabolic and hepatocellular changes in Atp7b-/- mice and whether ligand activation of nuclear receptors may lessen the hepatocellular dysfunction in Wilson’s disease. Future studies will address whether transcriptomic and proteomic signatures in Wilson’s disease overlap other chronic liver diseases.
Websites
Professional Development
- Career Advancement Series
- Workshop (Participant, 2017)
- Sponsor: Baylor College of Medicine
Selected Publications
- "Metabolic dysregulation in the Atp7b -/- Wilson's disease mouse model." 2020 Jan; Pubmed PMID: 31924743
- Clavia Ruth Wooton-Kee, Ajay K. Jain, Martin Wagner, Michael A. Grusak, Milton J. Finegold, Svetlana Lutsenko, David D. Moore "Elevated copper impairs hepatic nuclear receptor function in Wilson's disease." Journal of Clinical Investigation. 2015 Sep 1;125(9):3449-60. Pubmed PMID: 4588285
- 3. Pankowicz FP, Barzi M, Kim KH, Legras X, Martins CS, Wooton-Kee CR, Lagor WR, Marini JC, Elsea SH, Bissig-Choisat B, Moore DD, Bissig KD. "Rapid Disruption of Genes Specifically in Livers of Mice Using Multiplex CRISPR/Cas9 Editing." ; Pubmed PMID: 30170115
- Wagner M, Choi S, Panzitt K, Mamrosh JL, Lee JM, Zaufel A, Xiao R, Wooton-Kee R, Ståhlman M, Newgard CB, Borén J, Moore DD "Liver receptor homolog-1 is a critical determinant of methyl-pool metabolism." Hepatology. 2015 Aug 12; Pubmed PMID: 26267291
- Coy DJ, Wooton-Kee CR, Yan B, Sabeva NS, Su K, Graf GA, Vore M "ABCG5/ABCG8-independent biliary cholesterol excretion in lactating rats." Am J Physiol Gastrointestinal Liver Physiol. 2010 Apr 22;299(1):228-235. Pubmed PMID: 20413720
- Antony Athippozhy, Huang L, Wooton-Kee CR, Zhao T, Jungsuwadee P, Stromberg AJ, and Vore, M "Differential gene expression in liver and small intestine from lactating rats compared to age-matched virgin controls detects increased mRNA of cholesterol biosynthetic genes." BMC Genomics. 2011 Feb 3;12(95) Pubmed PMID: 3045338
- Wooton-Kee, C.R., Coy, D.J., Athippozhy, A.T., Jones, B.R., Zhao, T., and Vore, M "Mechanisms for increased expression of cholesterol 7 -hydroxylase (Cyp7A1) in lactating rats." Hepatology. 2010 Jan;51(1):277-285. Pubmed PMID: 2799537
- Wooton-Kee, C.R., Cohen, D.E., and Vore, M. "Increased cholesterol 7alpha-hydroxylase expression and size of the bile acid pool in the lactating rat." Am J Physiol Gastrointest Liver Physiol. 2008 Feb 21;294:1009-1016. Pubmed PMID: 2408447
- Wood, M., Ananthanarayanan, M., Jones, B., Wooton-Kee, R., Hoffman, T., Suchy, F.J., and Vore, M "Hormonal regulation of hepatic organic anion transporting polypeptides." Molecular Pharmacology. 2005 Jul;68(1):218-225. Pubmed PMID: 1463998
- Wooton-Kee, C.R., Boyanovsky, B.B., Nasser, M.S., de Villiers, W.J.S., and Webb, N.R. "Group V sPLA2 hydrolysis of low-density lipoprotein results in spontaneous particle aggregation and promotes macrophage foam cell formation." Arteriosclerosis, Thrombosis, and Vascular Bi. 2004;24(4):762-767.
- Tabb, A.L., Utsugi, T., Wooten-Kee, C.R., Sasaki, T., Edling, S.A., Gump, W., Kikuchi,Y., Ellis, S.R. "Genes encoding ribosomal proteins Rps0A/B of Saccharomyces cerevisiae interact with TOM1 mutants defective in ribosome synthesis." Genetics. 2001;157(3):1107-1116.
- Wooton-Kee, C.R., Clark, B.J. "Steroidogenic factor-1 influences protein-deoxyribonucleic acid interactions within the cyclic adenosine 3,5-monophosphate-responsive regions of the murine steroidogenic acute regulatory protein gene." Endocrinology. 2000;141(4):1345-1355.
- "Constitutive Androstane Receptor Differentially Regulates Bile Acid Homeostasis in Mouse Models of Intrahepatic Cholestasis." ; Pubmed PMID: 30620001
- "Xenobiotic Nuclear Receptor Signaling Determines Molecular Pathogenesis of Progressive Familial Intrahepatic Cholestasis." ; Pubmed PMID: 29718219
- "Targeted inactivation of copper transporter Atp7b in hepatocytes causes liver steatosis and obesity in mice." ; Pubmed PMID: 28428350
Memberships
- American Association for the Study of Liver Diseases
- Texas Medical Digestive Disease Center
- Dan L Duncan Comprehensive Cancer Center
Funding
- Nuclear Receptors as Novel Therapeutic Targets for Wilson's Disease - #1K01DK111716-01 (02/17/2017 - 01/31/2022) Grant funding from NIH/NIDDK
- NIH K01 Career Development Award
- Excessive Copper Levels Disrupt Hepatic Nuclear Receptor Function - #F32 DK089689-01A1 (10/01/2010 - 10/31/2012) Grant funding from NIH/NIDDK
- Ruth L. Kirschstein National Research Service Award for Individual Postdoctoral Fellow - F32 Award
- Copper Disruption of Nuclear Receptors and Zinc Therapy - #P30 DK056338 (02/28/2014 - 02/28/2015) Grant funding from Texas Medical Center Digestive Diseases Center, NIH/NIDDK
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