Dr. Oliver Hankinson's research focuses on the mechanism of carcinogenesis by environmental chemicals and the response of cells to reduced oxygen.
Specifically, Hankinson studies polycyclic aromatic hydrocarbons (found in cigarette smoke and smog), 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 also dimerizes with HIF-1a to form HIF-1 (Hypoxia Inducible Factor), which is the master regulator of the hypoxic response. Hankinson is studying the molecular mechanism of gene activation by HIF-1 and the role of HIF-1 in tumor angiogenesis and growth.
Current research projects include analyzing the mechanism of transcriptional activation by the AHR/ARNT and HIF-1a/ARNT dimers, particularly the potential roles of coactivator proteins in these processes; analyzing novel genes his group has identified that are required for inductions by AHR/ARNT and H1F-1a/ARNT; and determining the roles of AHR and ARNT in development, response to hypoxia and response to chemical carcinogens.
Selected Cancer-Related Publications:
Bui P, Solaimani P, Wu X, Hankinson O. 2,3,7,8-Tetrachlorodibenzo-p-dioxin treatment alters eicosanoid levels in several organs of the mouse in an aryl hydrocarbon receptor-dependent fashion. Toxicol Appl Pharmacol. 2012 Mar 1;259(2):143-51. doi: 10.1016/j.taap.2011.12.009. Epub 2011 Dec 20.
Beedanagari SR, Taylor RT, Bui P, Wang F, Nickerson DW, Hankinson O. Role of epigenetic mechanisms in differential regulation of the dioxin-inducible human CYP1A1 and CYP1B1 genes. Mol Pharmacol. 2010 Oct;78(4):608-16. Epub 2010 Jul 14.
Wang F, Zhang R, Wu X, Hankinson O. Roles of coactivators in hypoxic induction of the erythropoietin gene. PLoS One. 2010 Apr 2;5(4):e10002.
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 Feb;49(2):157-65.
Shi S, Yoon DY, Hodge-Bell KC, Bebenek IG, Whitekus MJ, Zhang R, Cochran AJ, Huerta-Yepez S, Yim SH, Gonzalez FJ, Jaiswal AK, Hankinson O. The aryl hydrocarbon receptor nuclear translocator (Arnt) is required for tumor initiation by benzo[a]pyrene. Carcinogenesis. 2009 Nov;30(11):1957-61. Epub 2009 Sep 15.