Education
- PhD: Biochemistry, University of Alabama Medical Center, Birmingham. 1982
Faculty Appointments
- 7/98 to Present - Associate Professor, Medicine
- 8/97 to Present - Toxicology Graduate Program Faculty
- 3/96 to Present - Graduate Faculty
- 1992 to 1998 - Assistant Professor, Department of Medicine, Division of Gastroenterology & Hepatology, University of Colorado Denver, Denver, CO
Committees and Responsibilities
- 1995 to present - American Society for Biochemistry and Molecular Biology
- 1998 to present - Society of Toxicology
- 2003 to 2004 - Vice President, Society of Toxicology, Mountain West Regional Chapter
- 2004 to 2005 - President, Society of Toxicology, Mountain West Regional Chapter
- 2002 to present - Advisory board for the NIEHS -ARCH program
- 2004 to present - Editorial Board of Molecular Pharmacology
- 2004 to present - American Society for Pharmacology and Experimental Toxicology
- 2000, 2001, 2003 - Reviewer, NIH Special Emphasis Study Sections
Research Interests
Dr. Quattrochi's laboratory is interested in the mechanisms regulating human cytochrome (CYP) P450 gene expression. Our work has focused on two such genes, CYP1A1 and CYP1A2 , that play a major role in the bioactivation of a large number of chemical carcinogens and environmental contaminants. These P450 enzymes are induced by halogenated and polycyclic aromatic hydrocarbons mediated through an intracellular receptor, the Aryl hydrocarbon Hydroxylase or Ah (dioxin)-receptor (AhR). One of our earlier significant findings was that dietary herbal and botanical agents can compete with toxins for binding the AhR, thus providing one plausible mechanism for dietary chemoprevention. A second interest of the laboratory is the effect of hepatitis C virus (HCV) on AhR-mediated signal transduction pathways. Our studies have shown that AhR signaling is altered in human hepatoma cells expressing the HCV subgenomic replicon. Using a combination of primary cultures of mammalian hepatocytes and novel HCV infected cell lines, we are exploring the molecular mechanisms by which environmental toxins and viral infections interact in a way that might contribute to HCV-associated liver pathogenesis. A third interest is the mechanisms regulating the expression of CYP3A4, a P450 that metabolizes more than 50% of clinical drugs. CYP3A4 is upregulated by a diverse number of structurally unrelated agents, including drugs and steroids, through activation of two nuclear receptors, PXR and CAR. A related focus is on the identification of other genes regulated through the PXR pathway. We have used gene expression analysis to profile genes regulated in rat liver by the PXR ligand, pregnenolone 16a-carbonitrile (PCN). We are presently focusing on one such gene, Myd118/GADD45b, that was highly induced by PCN in liver and lung. GADD45b is a member of a family of genes that has been shown to be induced by DNA damage and other genotoxic stresses, providing additional evidence that the activated PXR functions as a sensor of xenobiotic stress. Our long-term goal is to determine the mechanism by which the PXR functions in the pathway leading to induced GADD45b expression and to determine if PXR agonist can protect against hepatotoxic injury.
Representative Publications
- Williams SN, Shih H, Guenette DK, Pickwell GV, Brackney W, Denison MS and Quattrochi LC. Comparative studies on the effects of green tea extracts and individual tea catechins on human CYP1A gene expression. Chemico-Biological Interactions, 2000;128:211-229. (download PDF)
- Shaio T, Iwahashi M, Fortune J, Quattrochi LC, Bowman S, Wick M, Qadri I, and Simon FR. Structural and functional characterization of liver cell-specific activity of the human sodium/taurocholate cotransporter. Genomics 2000;69:203-213. (download PDF)
- Valerio LG Jr, Kepa JK, Pickwell GV, and Quattrochi LC. Induction of human NAD(P)H: quinine reductase (NQ01) gene expression by the flavonol quercetin. Toxicology Letters 2001;119:49-57. (download PDF)
- Quattrochi LC and Guzelian PS. CYP3A Regulation: From Pharmacology to Nuclear Receptors. Minireview, Drug Metabolism and Disposition 29, 615-622, 2001. (download PDF)
- Allen SW, Mueller L, Williams SN, Quattrochi LC, and Raucy JL. The use of a high volume screening procedure to assess the effects of dietary flavonoids on human CYP1A1 expression. Drug Metabolism and Disposition 29(8) 1074-9, 2001. (download PDF)
- Jimenez BD, Maldonado L, Dahl RH, Quattrochi LC, Guzelian PS. Ectopic expression of MHC class II genes (RT1.B(I) beta/alpha) in rat hepatocytes in vivo and in culture can be elicited by treatment with the pregnane X receptor agonists pregnenolone 16alpha-carbonitrile and dexamethasone. Life Sci. 2002 Jun 7;71(3):311-23. (download pdf)
- Pickwell, GV, Shih H, Quattrochi LC. Interaction of upstream stimulatory factor proteins with an E-box located within the human CYP1A2 5'-flanking gene contributes to basal transcriptional gene activation. Biochem. Pharmacol. 2003, 65(7): 1087-1096. (download PDF)
- Williams, SN, Pickwell, GV, and Quattrochi, LC. A Combination of Tea (Camellia senensis) Catechins is Required for Optimal Inhibition of Induced CYP1A Expression by Green Tea Extract. J Agric Food Chem 51(22):6627-6634, 2003. (download PDF)
- Black VH, Quattrochi LC. Molecular cloning of the guinea pig CYP1A2 gene 5’-flanking region, identification of functional AHRE and characterization of CYP1A2 expression in GPC16 cells. Drug Metabolism and Disposition, 32:595-602, 2004. (download PDF)
- Narvaez, MJ, Anderson, GR, Pickwell, GV, and Quattrochi, LC. Characterization of Adjacent E-box and Nuclear Factor 1-Like DNA Binding Sequence in the Human CYP1A2 Promoter, J Biochem Mol Toxicol 19:78-86, 2005. (download PDF)
- Anderson GR, Hasan A, Yin H, Qadri I, and Quattrochi LC. Regulation of the
CYP1A1 Gene by 2,3,7,8-Tetrachlorodibenzo-p-dioxin, but not b-Naphthoflavone or 3-Methylcholanthrene, is Altered in Hepatitis C Virus Replicon-Expressing Cells. Mol Pharmacol 70:1062-1070, 2006.