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Skaggs Phamacy Building
Primary Phone: (520) 6260219
Skaggs Phamacy Building
1703 E. Mabel
Primary Phone: (520) 6260219
PhD, North Carolina State University, 1997, Toxicology
BS, Brigham Young University, 1993, Zoology
- College Of Pharmacy
- College Of Public Health
Individual Variability in Drug Response and Adverse Drug Reactions,Transporter Regulation and Molecular Toxicology
Environmental Health Research & Expertise:
My laboratory has been focused on the effect of liver disease on the ability of an individual to metabolize and eliminate drugs and xenobiotics, as well as the mechanisms by which drug metabolizing enzymes and transporters are regulated by cellular stress. A major focus of my laboratory has been investigating the mechanisms of altered expression and activity of the major drug metabolizing enzymes and transporters during the progressive stages of nonalcoholic fatty liver disease. We have identified changes in the expression and functionality of several drug metabolizing enzymes in both rodent models and the human disease. We have recently discovered alterations in the expression and localization of key drug transporters in NASH resulting in altered disposition of drugs and xenobiotics. A major thrust of this work is an effort to identify patients at greater risk of developing adverse drug reactions due to altered pharmacokinetics and overall exposure. This work has led to the development of a non-invasive biomarker in a cohort of pediatric nonalcoholic fatty liver disease patients that specifically identifies those with NASH. My laboratory is now poised at the forefront of understanding drug disposition alterations in liver disease.
- Renal Xenobiotic Transporter Expression is Altered in Multiple Experimental Models of Nonalcoholic Steatohepatitis.
- Identification of a Functional Antioxidant Response Element within the Eighth Intron of the Human ABCC3 Gene.
- Systems Level Metabolic Phenotype of Methotrexate Administration in the Context of Non-alcoholic Steatohepatitis in the Rat.
- Increased susceptibility to methotrexate-induced toxicity in nonalcoholic steatohepatitis.
- Drug disposition alterations in liver disease: extrahepatic effects in cholestasis and nonalcoholic steatohepatitis.
- Xenobiotic transporter expression along the male genital tract.
- Synergistic interaction between genetics and disease on pravastatin disposition.
- Experimental nonalcoholic steatohepatitis increases exposure to simvastatin hydroxy acid by decreasing hepatic organic anion transporting polypeptide expression.
- Modeling human nonalcoholic steatohepatitis-associated changes in drug transporter expression using experimental rodent models.
- Selective and cytokine-dependent regulation of hepatic transporters and bile acid homeostasis during infectious colitis in mice.
- Circulating microRNA 122 in the methionine and choline-deficient mouse model of non-alcoholic steatohepatitis.
- Localization of multidrug resistance-associated proteins along the blood-testis barrier in rat, macaque, and human testis.
- The adaptive endoplasmic reticulum stress response to lipotoxicity in progressive human nonalcoholic fatty liver disease.
- Characterization of hepatocellular carcinoma related genes and metabolites in human nonalcoholic fatty liver disease.
- Differential regulation of hepatic organic cation transporter 1, organic anion-transporting polypeptide 1a4, bile-salt export pump, and multidrug resistance-associated protein 2 transporter expression in lymphocyte-deficient mice associates with interleukin-6 production.
- Downregulation of sulfotransferase expression and activity in diseased human livers.
- Basolateral uptake of nucleosides by Sertoli cells is mediated primarily by equilibrative nucleoside transporter 1.
- Alcohol cirrhosis alters nuclear receptor and drug transporter expression in human liver.
- Decreased hepatotoxic bile acid composition and altered synthesis in progressive human nonalcoholic fatty liver disease.
- Altered UDP-glucuronosyltransferase and sulfotransferase expression and function during progressive stages of human nonalcoholic fatty liver disease.
- The hepatic bile acid transporters Ntcp and Mrp2 are downregulated in experimental necrotizing enterocolitis.
- Altered arsenic disposition in experimental nonalcoholic Fatty liver disease.
- Genetics or environment in drug transport: the case of organic anion transporting polypeptides and adverse drug reactions.
- Molecular mechanism of altered ezetimibe disposition in nonalcoholic steatohepatitis.
- Genetic variation in the mouse model of Niemann Pick C1 affects female, as well as male, adiposity, and hepatic bile transporters but has indeterminate effects on caveolae.
- Variations in ATP-binding cassette transporter regulation during the progression of human nonalcoholic fatty liver disease.
- Analysis of global and absorption, distribution, metabolism, and elimination gene expression in the progressive stages of human nonalcoholic fatty liver disease.
- Drug metabolism alterations in nonalcoholic fatty liver disease.
- Constitutive activation of nuclear factor-E2-related factor 2 induces biotransformation enzyme and transporter expression in livers of mice with hepatocyte-specific deletion of Kelch-like ECH-associated protein 1.
- Vanadium pentoxide (V(2)O(5)) induced mucin production by airway epithelium.
- Cloning and characterization of human MUC19 gene.
- NF-κB mediates IL-1β- and IL-17A-induced MUC5B expression in airway epithelial cells.
- Diversity in antioxidant response enzymes in progressive stages of human nonalcoholic fatty liver disease.
- Drug transporter expression and localization in rat nasal respiratory and olfactory mucosa and olfactory bulb.
- Hepatic cytochrome P450 enzyme alterations in humans with progressive stages of nonalcoholic fatty liver disease.
- Experimental non-alcoholic fatty liver disease results in decreased hepatic uptake transporter expression and function in rats.
- Decreased apoptosis during CAR-mediated hepatoprotection against lithocholic acid-induced liver injury in mice.
- Constitutive androstane receptor-mediated changes in bile acid composition contributes to hepatoprotection from lithocholic acid-induced liver injury in mice.
- Effect of allyl alcohol on hepatic transporter expression: zonal patterns of expression and role of Kupffer cell function.
- Renal xenobiotic transporters are differentially expressed in mice following cisplatin treatment.
- Hepatic Mrp4 induction following acetaminophen exposure is dependent on Kupffer cell function.
- Tissue distribution, ontogeny and induction of the transporters Multidrug and toxin extrusion (MATE) 1 and MATE2 mRNA expression levels in mice.
- Drug metabolizing enzyme induction pathways in experimental non-alcoholic steatohepatitis.
- The Nrf2 activator oltipraz also activates the constitutive androstane receptor.
- Drug-metabolizing enzyme and transporter expression in a mouse model of diabetes and obesity.
- Minimal role of hepatic transporters in the hepatoprotection against LCA-induced intrahepatic cholestasis.
- Induction of Mrp3 and Mrp4 transporters during acetaminophen hepatotoxicity is dependent on Nrf2.
- Efflux transporter expression and acetaminophen metabolite excretion are altered in rodent models of nonalcoholic fatty liver disease.
- Induction of hepatobiliary efflux transporters in acetaminophen-induced acute liver failure cases.
- Molecular identification and functional characterization of rabbit MATE1 and MATE2-K.
- Induction of drug-metabolizing enzymes by garlic and allyl sulfide compounds via activation of constitutive androstane receptor and nuclear factor E2-related factor 2.
- Differential regulation of hepatic transporters in the absence of tumor necrosis factor-alpha, interleukin-1beta, interleukin-6, and nuclear factor-kappaB in two models of cholestasis.
- Regulation of transporter expression in mouse liver, kidney, and intestine during extrahepatic cholestasis.
- Sex differences in the mRNA, protein, and functional expression of organic anion transporter (Oat) 1, Oat3, and organic cation transporter (Oct) 2 in rabbit renal proximal tubules.
- Rhinovirus induces airway epithelial gene expression through double-stranded RNA and IFN-dependent pathways.
- Tissue distribution and hepatic and renal ontogeny of the multidrug resistance-associated protein (Mrp) family in mice.
- Liver disease with altered bile acid transport in Niemann-Pick C mice on a high-fat, 1% cholesterol diet.
- Differential expression of mouse hepatic transporter genes in response to acetaminophen and carbon tetrachloride.
- Xenobiotic and endobiotic transporter mRNA expression in the blood-testis barrier.
- Functional map of TEA transport activity in isolated rabbit renal proximal tubules. Previous years
- Induction of multidrug resistance protein 3 (mrp3) in vivo is independent of constitutive androstane receptor.
- Constitutive expression of various xenobiotic and endobiotic transporter mRNAs in the choroid plexus of rats.
- Endocrine regulation of rat organic anion transporters.
- Intestinal absorption of cadmium is associated with divalent metal transporter 1 in rats.
- Gender-specific and developmental influences on the expression of rat organic anion transporters.
- Tissue expression, ontogeny, and inducibility of rat organic anion transporting polypeptide 4.
- Tissue distribution and chemical induction of multiple drug resistance genes in rats.
- Lipopolysaccharide-mediated regulation of hepatic transporter mRNA levels in rats.
- Down-regulation of mouse organic anion-transporting polypeptide 4 (Oatp4; Oatp1b2; Slc21a10) mRNA by lipopolysaccharide through the toll-like receptor 4 (TLR4).
- Influence of acetaminophen vehicle on regulation of transporter gene expression during hepatotoxicity.
- Genes of the antioxidant response undergo upregulation in a rodent model of nonalcoholic steatohepatitis.
- Gender divergent expression of Nqo1 in Sprague Dawley and August Copenhagen x Irish rats.
- Induction of drug metabolism enzymes and transporters by oltipraz in rats.
- Nuclear factor-E2-related factor 2 expression in liver is critical for induction of NAD(P)H:quinone oxidoreductase 1 during cholestasis.
- Enzyme induction and cytotoxicity in human hepatocytes by chlorpyrifos and N,N-diethyl-m-toluamide (DEET).
- Organ distribution of multidrug resistance proteins 1, 2, and 3 (Mrp1, 2, and 3) mRNA and hepatic induction of Mrp3 by constitutive androstane receptor activators in rats.
- Measuring altered disposition of xenobiotics in experimental models of liver disease.