Oliver Hankinson, Ph.D.

Mailing Address:
UCLA Path & Lab Med
BOX 951732, 10833 Le Conte Ave, 13-244 Factor Bldg
Los Angeles, CA 90095

Affiliations
Affiliations
Distinguished Research Professor, Director of Molecular Toxicology IDP, Environmental Health Sciences
Professor, Pathology and Laboratory Medicine
Member, Gene Regulation GPB Home Area, JCCC Cancer and Stem Cell Biology Program Area, JCCC Molecular Epidemiology Program Area, Molecular Pharmacology GPB Home Area
Faculty, Cellular and Molecular Pathology PhD Program
Research Interests
Research Area: Carcinogenesis, Hypoxia. Research Interests: Dr. Hankinson's research focuses on several areas. In one line of investigation he studies the mechanism of carcinogenesis by polycyclic aromatic hydrocarbons (found in cigarette smoke and smog) and dioxin (a widespread pollutant), and related compounds. Carcinogenesis by these compounds depends upon their binding to the aryl hydrocarbon receptor (AHR) and the subsequent dimerization of AHR with the ARNT protein. He is studying the molecular mechanism of activation of gene transcription by the liganded AHR/ARNT dimer (including the role of coactivator proteins in this process). In addition, he studies the roles of AHR and ARNT in animal models of carcinogenesis. ARNT dimerizes with HIF-1a to form HIF-1 (Hypoxia Inducible Factor), which is the master regulator of the hypoxic response. Dr. Hankinson is also studying the molecular mechanism of gene activation by HIF-1 and the role of HIF-1 in tumor angiogenesis and growth. He also studies CYP2S1, a novel human cytochrome P450 that his group discovered and which appears to play a critical role in the metabolism of prostaglandins and other eicosanoids. Current research focuses on the following : Analyzing the mechanism of transcriptional activation by the AHR/ARNT and HIF-1a/ARNT dimers, particularly the potential roles of coactivator proteins and covalent histone modification in theses processes. Determining the role of ARNT in response to hypoxia, and response to chemical carcinogens, via analysis of ARNT "conditional knockout" mice. Studying the role of CYP2S1 in the development of cancer and asthma.
Biography

Dr. Hankinson is a Professor of Pathology and Laboratory Medicine, and Director of the Doctoral Program in Molecular Toxicology. He received his Ph.D. in genetics from Cambridge University, England, in 1972. He did postdoctoral research in mammalian cell genetics at Harvard University, the University of Colorado, and the University of California, Berkeley, before joining the UCLA faculty in 1979. He was Director of the Carcinogenesis program of the UCLA Jonsson Comprehensive Cancer Center from 1994 to 2003, and Vice-Chair for Research of the Department of Pathology from 1997 to 2003. In 2000 he was founding director of the Molecular Toxicology Ph.D. program. He received the 2011 Distinguished Toxicology Award from the Society of Toxicology.

Publications
Solaimani Parrisa, Damoiseaux Robert, Hankinson Oliver Genome Wide RNAi High Throughput Screen Identifies Proteins Necessary for the AHR-Dependent Induction of CYP1A1 by 2,3,7,8-Tetrachlorodibenzo-ρ-dioxin. Toxicological sciences : an official journal of the Society of Toxicology. 2013; .
Ingelman-Sundberg Magnus, Zhong Xiaobo, Hankinson Oliver, Beedanagari Sudheer, Yu Ai-Ming H, Peng Lai, Osawa Yoichi Potential Role of Epigenetic Mechanisms in the Regulation of Drug Metabolism and Transport. Drug metabolism and disposition: the biological fate of chemicals. 2013; .
Bui Peter, Solaimani Parrisa, Wu Xiaomeng, Hankinson Oliver 2,3,7,8-Tetrachlorodibenzo-p-dioxin treatment alters eicosanoid levels in several organs of the mouse in an aryl hydrocarbon receptor-dependent fashion. Toxicology and applied pharmacology. 2012; 259(2): 143-51.
Bebenek Ilona G, Solaimani Parrisa, Bui Peter, Hankinson Oliver CYP2S1 is negatively regulated by corticosteroids in human cell lines. Toxicology letters. 2012; 209(1): 30-4.
Baay-Guzman Guillermina J, Bebenek Ilona G, Zeidler Michelle, Hernandez-Pando Rogelio, Vega Mario I, Garcia-Zepeda Eduardo A, Antonio-Andres Gabriela, Bonavida Benjamin, Riedl Marc, Kleerup Eric, Tashkin Donald P, Hankinson Oliver, Huerta-Yepez Sara HIF-1 expression is associated with CCL2 chemokine expression in airway inflammatory cells: implications in allergic airway inflammation. Respiratory research. 2012; 13: 60.
Quesada Arnulfo, Bui Peter H, Homanics Gregg E, Hankinson Oliver, Handforth Adrian Comparison of mibefradil and derivative NNC 55-0396 effects on behavior, cytochrome P450 activity, and tremor in mouse models of essential tremor. European journal of pharmacology. 2011; 39(2): .
Bui Peter, Imaizumi Satoshi, Beedanagari Sudheer Reddy, Reddy Srinivasa T, Hankinson Oliver Human CYP2S1 metabolizes cyclooxygenase- and lipoxygenase-derived eicosanoids. Drug metabolism and disposition: the biological fate of chemicals. 2011; 39(2): 180-90.
Shi S, Yoon DY, Hodge-Bell K, Huerta-Yepez S, Hankinson O. Aryl hydrocarbon nuclear translocator (hypoxia inducible factor 1beta) activity is required more during early than late tumor growth. Mol Carcinog. 2010; 49(2): 157-65.
Beedanagari Sudheer R, Taylor Robert T, Hankinson Oliver Differential regulation of the dioxin-induced Cyp1a1 and Cyp1b1 genes in mouse hepatoma and fibroblast cell lines. Toxicology letters. 2010; 194(1-2): 26-33.
Beedanagari Sudheer R, Taylor Robert T, Bui Peter, Wang Feng, Nickerson Derek W, Hankinson Oliver Role of epigenetic mechanisms in differential regulation of the dioxin-inducible human CYP1A1 and CYP1B1 genes. Molecular pharmacology. 2010; 78(4): 608-16.
Wang Feng, Zhang Ruixue, Wu Xiaomeng, Hankinson Oliver Roles of coactivators in hypoxic induction of the erythropoietin gene. PloS one. 2010; 5(4): e10002.
Bui, P.H. Hsu, E.L. Hankinson, O. Fatty Acid Hydroperoxides Support CYP2S1-Mediated Bioactivation of Benzo[a]pyrene7,8-dihydrodiol. Mol Pharmacol. 2009; [Epub ahead of print].
Bui Peter H, Hsu Erin L, Hankinson Oliver Fatty acid hydroperoxides support cytochrome P450 2S1-mediated bioactivation of benzo[a]pyrene-7,8-dihydrodiol. Molecular pharmacology. 2009; 76(5): 1044-52.
Bui, P.H. Hankinson, O. Functional Characterization of Human Cytochrom P450 2S1 Using a Synthetic Gene-Expressed Protein in E.Coli. Mol. Pharmacol. 2009; [Epub ahead of print] .
Bui Peter H, Hankinson Oliver Functional characterization of human cytochrome P450 2S1 using a synthetic gene-expressed protein in Escherichia coli. Molecular pharmacology. 2009; 76(5): 1031-43.
Hsu, E. L. Chen, N. Westbrook, A. Wang, F. Zhang, R. Taylor, R. T. Hankinson, O. Modulation of CXCR4, CXCL12, and Tumor Cell Invasion Potential In Vitro by Phytochemicals. J Oncol. 2009; 2009(number): 491985.
Hsu Erin L, Chen Natalie, Westbrook Aya, Wang Feng, Zhang Ruixue, Taylor Robert T, Hankinson Oliver Modulation of CXCR4, CXCL12, and Tumor Cell Invasion Potential In Vitro by Phytochemicals. Journal of oncology. 2009; 2009(2): 491985.
Hankinson, O. Repression of aryl hydrocarbon receptor transcriptional activity by epidermal growth factor. Mol Interv. 2009; 9(3): 116-8.
Hankinson Oliver Repression of aryl hydrocarbon receptor transcriptional activity by epidermal growth factor. Molecular interventions. 2009; 9(3): 116-8.
Beedanagari, S. R. Bebenek, I. Bui, P. Hankinson, O. Resveratrol inhibits dioxin-induced expression of human CYP1A1 and CYP1B1 by inhibiting recruitment of the aryl hydrocarbon receptor complex and RNA polymerase II to the regulatory regions of the corresponding genes. Toxicol Sci. 2009; 110(1): 61-7.
Beedanagari Sudheer R, Bebenek Ilona, Bui Peter, Hankinson Oliver Resveratrol inhibits dioxin-induced expression of human CYP1A1 and CYP1B1 by inhibiting recruitment of the aryl hydrocarbon receptor complex and RNA polymerase II to the regulatory regions of the corresponding genes. Toxicological sciences : an official journal of the Society of Toxicology. 2009; 110(1): 61-7.
Taylor, R. T. Wang, F. Hsu, E. L. Hankinson, O. Roles of coactivator proteins in dioxin induction of CYP1A1 and CYP1B1 in human breast cancer cells. Toxicol Sci. 2009; 107(1): 1-8.
Taylor Robert T, Wang Feng, Hsu Erin L, Hankinson Oliver Roles of coactivator proteins in dioxin induction of CYP1A1 and CYP1B1 in human breast cancer cells. Toxicological sciences : an official journal of the Society of Toxicology. 2009; 107(1): 1-8.
Shi, S. Yoon, D. Hodge-Bell, K. Bebenek, I. Whitekus, M. Zhang, R. Cochran, A. Huerta Yepez, S. Yim, S.-H. Gonzalez, F.J. Jaiswal, A. Hankinson, O. The Aryl Hydrocarbon Receptor Nuclear Translocator (Arnt) is required for tumor initiation by benzo(a)pyrene. Carcinogenesis. 2009; [Epub ahead of print] .
Shi Shengli, Yoon Diana Y, Hodge-Bell Kimberly C, Bebenek Ilona G, Whitekus Michael J, Zhang Ruixue, Cochran Alistair J, Huerta-Yepez Sara, Yim Sun-Hee, Gonzalez Frank J, Jaiswal Anil K, Hankinson Oliver The aryl hydrocarbon receptor nuclear translocator (Arnt) is required for tumor initiation by benzo[a]pyrene. Carcinogenesis. 2009; 30(11): 1957-61.
Buchler, P. Reber, H. A. Tomlinson, J. S. Hankinson, O. Kallifatidis, G. Friess, H. Herr, I. Hines, O. J. Transcriptional regulation of urokinase-type plasminogen activator receptor by hypoxia-inducible factor 1 is crucial for invasion of pancreatic and liver cancer. Neoplasia. 2009; 11(2): 196-206.
Hsu, E. L. Chen, N. Westbrook, A. Wang, F. Zhang, R. Taylor, R. T. Hankinson, O. CXCR4 and CXCL12 down-regulation: a novel mechanism for the chemoprotection of 3,3'-diindolylmethane for breast and ovarian cancers. Cancer Lett. 2008; 265(1): 113-23.
Bui, P. H. Quesada, A. Handforth, A. Hankinson, O. The mibefradil derivative NNC55-0396, a specific T-type calcium channel antagonist, exhibits less CYP3A4 inhibition than mibefradil. Drug Metab Dispos. 2008; 36(7): 1291-9.
Bui Peter H, Quesada Arnulfo, Handforth Adrian, Hankinson Oliver The mibefradil derivative NNC55-0396, a specific T-type calcium channel antagonist, exhibits less CYP3A4 inhibition than mibefradil. Drug metabolism and disposition: the biological fate of chemicals. 2008; 36(7): 1291-9.
Hankinson, O. Why does ARNT2 behave differently from ARNT?. Toxicol Sci. 2008; 103(1): 1-3.
Rivera, S. P. Wang, F. Saarikoski, S. T. Taylor, R. T. Chapman, B. Zhang, R. Hankinson, O. A novel promoter element containing multiple overlapping xenobiotic and hypoxia response elements mediates induction of cytochrome P4502S1 by both dioxin and hypoxia. J Biol Chem. 2007; 282(15): 10881-93.
Hsu, E. L. Yoon, D. Choi, H. H. Wang, F. Taylor, R. T. Chen, N. Zhang, R. Hankinson, O. A proposed mechanism for the protective effect of dioxin against breast cancer. Toxicol Sci. 2007; 98(2): 436-44.
Wang, F. Shi, S. Zhang, R. Hankinson, O. Comparative microarray analysis of gene expression in mouse Hepa-1c1c7 and B mutant cell lines - the effect of the aromatic hydrocarbon receptor on the phenotype of the cells in the absence of exogenous ligands. Gene Regulation and Systems Biology 2007; 1: 49-56.
Rivera, S. P. Saarikoski, S. T. Sun, W. Hankinson, O. Identification of novel dioxin-responsive genes by representational difference analysis. Xenobiotica. 2007; 37(3): 271-9.
Wang, F. Zhang, R. Xia, T. Hsu, E. Cai, Y. Gu, Z. Hankinson, O. Inhibitory effects of nitric oxide on invasion of human cancer cells. Cancer Lett. 2007; 257(2): 274-82.
Wang, F. Shi, S. Zhang, R. Hankinson, O. Identifying target genes of the aryl hydrocarbon receptor nuclear translocator (Arnt) using DNA microarray analysis. Biol Chem. 2006; 387(9): 1215-8.
Saarikoski, S. T. Rivera, S. P. Hankinson, O. Husgafvel-Pursiainen, K. CYP2S1: a short review. Toxicol Appl Pharmacol. 2005; 207(2 Suppl): 62-9.
Rivera, S. P. Choi, H. H. Chapman, B. Whitekus, M. J. Terao, M. Garattini, E. Hankinson, O. Identification of aldehyde oxidase 1 and aldehyde oxidase homologue 1 as dioxin-inducible genes. Toxicology. 2005; 207(3): 401-9.
Hankinson, O. Role of coactivators in transcriptional activation by the aryl hydrocarbon receptor. Arch Biochem Biophys. 2005; 433(2): 379-86.
Fretland, A. J. Safe, S. Hankinson, O. Lack of antagonism of 2,3,7,8-tetrachlorodibenzo-p-dioxin's (TCDDs) induction of cytochrome P4501A1 (CYP1A1) by the putative selective aryl hydrocarbon receptor modulator 6-alkyl-1,3,8-trichlorodibenzofuran (6-MCDF) in the mouse hepatoma cell line Hepa-1c1c7. Chem Biol Interact. 2004; 150(2): 161-70.
Beischlag, T. V. Taylor, R. T. Rose, D. W. Yoon, D. Chen, Y. Lee, W. H. Rosenfeld, M. G. Hankinson, O. Recruitment of thyroid hormone receptor/retinoblastoma-interacting protein 230 by the aryl hydrocarbon receptor nuclear translocator is required for the transcriptional response to both dioxin and hypoxia. J Biol Chem. 2004; 279(52): 54620-8.
Wang, S. Ge, K. Roeder, R. G. Hankinson, O. Role of mediator in transcriptional activation by the aryl hydrocarbon receptor. J Biol Chem. 2004; 279(14): 13593-600.
Wang, F. Zhang, R. Beischlag, T. V. Muchardt, C. Yaniv, M. Hankinson, O. Roles of Brahma and Brahma/SWI2-related gene 1 in hypoxic induction of the erythropoietin gene. J Biol Chem. 2004; 279(45): 46733-41.
Anilkumar, G. Rajasekaran, S. A. Wang, S. Hankinson, O. Bander, N. H. Rajasekaran, A. K. Prostate-specific membrane antigen association with filamin A modulates its internalization and NAALADase activity. Cancer Res. 2003; 63(10): 2645-8.
Wang, S. Hankinson, O. Functional involvement of the Brahma/SWI2-related gene 1 protein in cytochrome P4501A1 transcription mediated by the aryl hydrocarbon receptor complex. J Biol Chem. 2002; 277(14): 11821-7.
Rivera, S. P. Saarikoski, S. T. Hankinson, O. Identification of a novel dioxin-inducible cytochrome P450. Mol Pharmacol. 2002; 61(2): 255-9.
Saarikoski, S. T. Rivera, S. P. Hankinson, O. Mitogen-inducible gene 6 (MIG-6), adipophilin and tuftelin are inducible by hypoxia. FEBS Lett. 2002; 530(1-3): 186-90.
Beischlag, T. V. Wang, S. Rose, D. W. Torchia, J. Reisz-Porszasz, S. Muhammad, K. Nelson, W. E. Probst, M. R. Rosenfeld, M. G. Hankinson, O. Recruitment of the NCoA/SRC-1/p160 family of transcriptional coactivators by the aryl hydrocarbon receptor/aryl hydrocarbon receptor nuclear translocator complex. Mol Cell Biol. 2002; 22(12): 4319-33.
Anttila, S. Tuominen, P. Hirvonen, A. Nurminen, M. Karjalainen, A. Hankinson, O. Elovaara, E. CYP1A1 levels in lung tissue of tobacco smokers and polymorphisms of CYP1A1 and aromatic hydrocarbon receptor. Pharmacogenetics. 2001; 11(6): 501-9.
Heo, Y. Saxon, A. Hankinson, O. Effect of diesel exhaust particles and their components on the allergen-specific IgE and IgG1 response in mice. Toxicology. 2001; 159(3): 143-58.
Yoon, D. Y. Buchler, P. Saarikoski, S. T. Hines, O. J. Reber, H. A. Hankinson, O. Identification of genes differentially induced by hypoxia in pancreatic cancer cells. Biochem Biophys Res Commun. 2001; 288(4): 882-6.
Roth, M. D. Marques-Magallanes, J. A. Yuan, M. Sun, W. Tashkin, D. P. Hankinson, O. Induction and regulation of the carcinogen-metabolizing enzyme CYP1A1 by marijuana smoke and delta (9)-tetrahydrocannabinol. Am J Respir Cell Mol Biol. 2001; 24(3): 339-44.
Lei, X. D. Chapman, B. Hankinson, O. Loss of cyp1a1 messenger rna expression due to nonsense-mediated decay. Mol Pharmacol. 2001; 60(2): 388-93.