Faculty

Yu-Jui Yvonne Wan, PhD

Joy McCann Professor of Pharmacology, Toxicology and Therapeutics
Director of the Liver Center
Joint Appointment in Pathology and Laboratory Medicine                                      
Division of Cancer & Developmental Biology     

Ph.D.: Hahnemann University School of Medicine, PA, 1983
Postdoctoral: National Institutes of Health, Bethesda, MD 1989

Email: ywan @ kumc.edu
Pharmacology bio page
Liver Center web site

Ph.D. students are welcome. Contact me for more info.

The major focus of Dr. Wan's research for the past decade has been retinoic acid and its receptors. She has demonstrated that retinoic and its receptor play a pivotal role in growth, differentiation, apoptosis, proliferation, and carcinogenesis. To study the in vivo function of the retinoid x receptor (RXRa) in liver, her laboratory has generated a tissue-specific knockout mouse model.

The study revealed that fatty acid, cholesterol, carbohydrate, amino acid, bile acid, steroid and xenobiotic metabolic pathways are compromised in hepatocyte RXRa -deficient mice, indicating that RXRa plays a key role in many biochemical and metabolic pathways. Using this mouse model, Dr. Wan has recently identified a large number of RXRa target genes in liver by DNA microarray analysis. Dr. Wan has also made major contributions in basic and clinical studies of alcoholic liver disease. Her studies have focused on the role of S-adenosyl methionine (SAM), a precursor of glutathione and an important antioxidant, in alcoholic liver disease. SAM has been implicated in the pathogenesis of alcoholic hepatitis.

Her studies have revealed that SAM synthesis and metabolism are disturbed in the RXRa -deficient hepatocytes, resulting in a 50% reduction of glutathione levels. This suggests a close relationship among RXRa , SAM, and alcoholic liver disease. The major goal of Dr. Wan's clinical study of alcoholic liver disease focuses on the identification of genetic risk factors for alcoholism in Mexican Americans. She has identified unique genetic patterns that might be responsible, in part, for the heightened risk for alcoholism and alcohol associated health problems in this population.

Lab Members

	Xiaoxia Yang, Ph.D. post doctoral fellow xyang@kumc.edu Research interests: My research involves studying the role of nuclear receptors in hepatocyte proliferation during liver regeneration and investigation of circadian patterns involved in lipid homeostasis.
	Kun Wang, Ph.D. post doctoral fellow kwang@kumc.edu Research interests: I am working on retinoic acid and its receptors.
	Hui Yang, M.S. research assistant hyang2@kumc.edu Research interests:CYP2E1 metabolizes a large number of endogenous or exogenous compounds including carcinogens, alcohol and drugs. I study the cellular mechanisms involved in the induction and regulation of CYP2E1.
	Maxwell Gyamfi, Ph.D. post doctoral fellow mgyamfi@kumc.edu Research interests: My research project in Dr.Wan’s Laboratory is focused on identifying the relationship between the nuclear receptor, retinoid X receptor α (RXRα) and S-adenosylmethionine homeostasis which may play a role in alcohol-induced liver injury and nonalcoholic fatty liver disease. The combination of methionine/choline-deficient and ethanol-containing diets are being used to achieve the aims of this research project. Our published data have clearly demonstrated the significant role of hepatocyte RXRα in the development of alcoholic liver disease (ALD). We have also illustrated the common as well as the differential molecular mechanisms by which ALD and non-alcoholic steatohepatitis are developed. Our most recent data has identified for the first time the involvement of RXRα in the regulation of inflammatory signaling.
	Chui Li Yeh, Ph.D. post doctoral fellow cyeh@kumc.edu Research interests: I am studying microRNA by culturing primary hepatocytes and infecting them with inhibitors to see how this alters their expression.
	Yanlei Du, Ph.D. post doctoral fellow ydu@kumc.edu Research interests: I explore genetic risk factors for alcoholism.
	Pengli Bu, M.S. graduate student pbu@kumc.edu Research interests: I am studying retinoid signaling and nuclear receptors and the role they play in liver cancer.
	Lin He Technician LHE@kumc.edu
	Barbara Brede, MPA Laboratory Manager bbrede@kumc.edu

 

Recent Publications

1. Gyamfi M, Wan Y-J. The effect of ethanol, ethanol metabolizing enzyme inhibitors, and vitamin E on regulating glutathione, glutathione S-transferase, and S-adenosylmethionine in mouse primary hepatocyte. Hepatology Research, 35: 53-61, 2006.
2. Wang K, Mendy AL, Dai G, Luo H, He L, Wan Y-J.  Retinoids Activate the RXR/SXR-mediated Pathway and Induce the Endogenous CYP3A4 Activity in Huh7 Human Hepatoma Cells. Toxicological Sciences, 92: 51-60, 2006.
3. Wan Y-J, Mostafa ZB. Inhibition of carrageenan-induced cutaneous inflammation by PPAR agonists is dependent on hepatocyte-specific retinoids x receptor alpha. PPAR Journal, Volume 2006, Article ID 96341, 1-6.
4. Nakamoto K, Wang S, Jenison RD, Guo G, Klaassen CD, Wan Y-J, Zhong X. Linkage disequilibrium blocks, haplotype structure, and htSNPs of human CYP7A1 gene, Biomedical Central Genetics, 7: 29, 2006.
5. Gyamfi M, Dai G, Kocsis M, He L, Mendy A, Wan Y-J. The role of retinoid X receptor alpha (RXRα) in regulating alcohol detoxification mediated by phase I and phase II enzymes. Journal of Pharmacology and Experimental Therapeutics, 319: 360-368, 2006.
6. Luo H, Wan Y-J. Polymorphism of genes encoding phase I enzymes in Mexican Americans- An ethnic comparison study. Current Pharmacogenomics, 4: 345-353, 2006.
7. Nakamoto K, Kidd JR, Luo H, Jenison RD, Klaassen CD, Wan Y-J, Zhong X. Genotyping and haplotyping of CYP2C19 functional alleles on thin-film biosensor chips. Pharmacogenomics and Genetics, 17:103-114, 2007.
8. Wortham M, Czerwinsky M, He L, Parkinson A, Wan Y-J. Expression of CAR, HNFα, and POR genes determines interindividual variability in basal expression and activity of a broad scope of xenobiotic metabolism genes in the human. Drug Metabolism and Disposition, Vol.3, No. 9, 2007.
9. Yang M, Tsuang J, Wan Y-J. A haplotype analysis of CYP2E1 polymorphisms in relation to alcoholic phenotypes in Mexican Americans. Alcoholism Clinical and Experimental Research, In press, 2007.
10. Dai G, He L, Bu P, Wan Y-J.  Pregnane X receptor is essential for normal progression of liver regeneration. Hepatology, 47(4):1277-1287, 2007.
11. Bu P, Wan Y-J. Fenretinide-induced aoptosis of Huh-7 hepatocellular carcinoma is retinoic acid receptor β dependent. BMC Cancer, 7(1):236, 2007.
12. Gyamfi M, Damjanov I, French S, Wan Y-J. The pathogenesis of ethanol versus methionine and choline deficient diet-induced liver injury. Biochemical Pharmacology, 75(4):981-985, 2008.
13. Gyamfi M, He L, French S, Damjanov I, Wan Y-J. Hepatocyte retinoid X receptor α-dependent regulation of lipid homeostasis and inflammatory cytokine expression contributes to alcohol-induced liver injury. Journal of Pharmacology and Experimental Therapeutics, 324(2):443-453, 2008.
14. Wang K, Wan Y-J. Nuclear receptors and inflammatory diseases. Experimental Biology and Medicine, 2008 Mar 28 e-publication ahead of print.
15. Yang X, Alnouti Y, Wan Y-J. Application of an improved HPLC-MS/MS method to study the gender difference in hepatic retinoid contents. Manuscript submitted, 2007.
16. Chen S, Wang K, Wan Y-J. Retinoids trans-activate the RXR/CAR-mediated pathway and induce CYP3A. Manuscript submitted, 2007.
17. Wang K, Chen S, Wan Y-J. Retinoids induce cytochrome P4503A4 through RXR/VDR-mediated pathway. Manuscript submitted, 2007.
18. Wortham M, He L, Gyamfi M, Copple BL, Wan YJ. The transition from fatty liver to NASH associates with SAMe depletion in de/db mice fed a methionine choline-deficient diet. Digestive Diseases Sciences, 2008 Feb 26 e-publication ahead of print.