Research Interests
Retinoic acid and its receptors, xenobiotic metabolism,
alcoholic liver disease, hepato carcinogenesis,
pharmacogenetic studies
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.
Wan Y-J, An D, Cai Y, Repa JJ, Chen H-P, Flores M, Postic C, Magnuson MA, Chen J, Chien KR, French S, Mangelsdorf DJ, Sucov HM. Hepatocyte-specific mutation establishes RXRa as a heterodimeric integrator of multiple physiological processes in the liver. Molecular and Cellular Biology 20: 4436-4444, 2000.
Wan Y-J, Cai Y, Lungo W, Fu P, Locker J, French S, Sucov HM. Peroxisome proliferator-activated receptor a-mediated pathways are altered in hepatocyte-specific retinoid x receptor a-deficient mice. Journal Biological Chemistry 275: 28285-28290, 2000.
WanY-J, Poland RE, Han G, Konishi T, Zheng Y-P, Lin K-M. Analysis of the CYP2D6 gene polymorphism and enzyme activity in Africa-Americans in Southern California. Pharmacogenetics 11 (6): 489-499, 2001.
Mendoza R, Wan Y-J, Poland RE, Smith M, Zheng Y, Berman N, Lin K-M. CYP2D6 polymorphism in a Mexican American population. Clinical Pharmacology and Therapeutics 70: 552-560, 2001.
Konishi T, Smith JL, Lin K-M, Wan Y-J. Influence of genetic admixture on polymorphisms of alcohol-metabolizing enzymes: analyses of mutations on the CYP2E1, ADH2, ADH3, and ALDH2 genes in a Mexican American population Living in the Los Angeles area. Alcohol and Alcoholism, 38: 93-94, 2003.
Konishi T, Calvillo M, Leng A-S, Feng J, Lee T, Lee H, Smith JL, Sial SH, Berman N, French S, Eysselein V, Lin K-M, Wan Y-J. The ADH3*2 and CYP2E1 c2 alleles increase the risk of alcoholism in Mexican American men. Experimental and Molecular Pathology, 74: 183-189, 2003.
Wan Y-J, Han G, Cai Y, Dai T, Konishi T, Leng A-S. Hepatocyte RXR -deficient mice have reduced food intake, increased body weight, and improved glucose tolerance. Endocrinology, 144(2): 605-611, 2003.
Bentinger M, Turunen M, Zhang X-X, Wan Y-J, Dallner G. Involvement of retinoid X receptor in coenzyme Q metabolism. J Molecular Biology, 326: 795-803, 2003.
French S, Wan Y-J. Nutritional factors in the pathogenesis of alcoholic liver disease: an update. Nutrition and Alcohol, in press, 2003.
Cai Y, Dai T, Ao Y, Konishi T, Chuang K-H, Lue Yanhe, Chang C, Wan Y-J. Cytochorme P450 genes are differentially expressed in female and male hepatocyte RXR -deficient mice. Endocrinology, 144: 2311-2318, 2003.
Perlis RH, Mischoulon D, Smoller JW, Wan Y-J, Lamon-Fava S, Lin K-M, Rosenbaum JF, Fava M. Serotonin transporter polymorphisms and adverse effects with fluoxetine treatment. Biological Psychiatry 54: 879-883, 2003.
Cherrington NJ, Slitt AL, Maher JM, Zhang XX, Zhang J, Huang W, Wan Y-J, Moore DD, Klaassen CD. Induction of multidrug resistance protein 3 (mrp3) in vivo is independent of constitutive androstane receptor. Drug Metab Dispos 31: 1315-1319, 2003.
Dai T, Wu Y, Leng A, Ao Y, Robel RCV, Lu SC, French SW, Wan Y-J. RXR regulated liver SAMe and GSH levels influence the susceptibility to alcohol induced hepatotoxicity. Experimental and Molecular Pathology 75: 194-200, 2003.
Konishi T, Calvillo M, Leng A-S, Lin K-M, Wan Y-J. Polymorphisms of the dopamine D2 receptor, serotonin transporter, and GABAA Receptor B3 subunit genes and alcohol dependence in Mexican Americans. Alcohol 32: 45-52, 2004.
Wu Y, Cai Y, Aguilo J, Dai T, Ao Y, Wan Y-J. RXR mRNA expression is associated with cell proliferation and cell cycle regulation in Hep3B cell. Experimental and Molecular Pathology 76: 24-28, 2004.
Leng A-S, Calvillo M, Konishi T, Dai T, Guzman GD, Pineda E, Lin K-M, Tsuang J, Wan Y-J. Characterization and drinking patterns in Mexican American men. Addictive Disorders and Their Treatment 3: 14-17, 2004.
Wu Y, Zhang X, Bardag-Gorce F, Robel R, Aguilo J, Chen L, Zeng Y, Hwang K, French SW, Lu SC, Wan Y-J. Retinoid x receptor alpha regulates glutathione homeostasis and xenobiotic detoxification processes in mouse liver. Molecular Pharmacology 65: 550-557, 2004.
Konishi T, Luo H, Calvillo M, Mayo M, Lin K-M, Wan Y-J. ADH1B*2, ADH1C*1, DRD2 (-141C Ins) and 5-HTTLPR are associated with alcoholism in Mexican American Men living in Los Angeles. Alcoholism: Clinical and Experimental Research, 32: 45-52, 2004.
Luo H-R, Aloumanis V, Lin K-H, Gurwitz D, Wan Y-J. Polymorphisms of CYP2C19 and CYP2D6 in Israeli ethnic groups. American Journal of PharmacoGenomic, in press, 2004.
Yu-Jui Yvonne Wan, Ph.D.
Professor
Department of Pharmacology, Toxicology and Therapeutics
The University of Kansas Medical Center
MS 1018
3901 Rainbow Boulevard
Kansas City, Kansas 66160
Phone: (913) 588-9111
Fax: (913) 588-7501
Email: ywan@kumc.edu
Curriculum Vitae in PDF Format
Updated 9/5/08
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The University of Kansas Medical Center