Mammary carcinogenesis, Lung Carcinogenesis, Mechanisms of toxicity, Genetic susceptibility, Toxicogenomics, Tumor suppressor genes, Functional genomics, Signal transduction, Transcriptional regulation, Mutagenesis

Dr. Zarbl’s research has focused largely on toxicogenomics and functional genomics, carcinogenesis, molecular and cellular biology, and toxicology.  Specifically this has included work to understand molecular mechanisms of chemical carcinogenesis and the genetic basis for differential susceptibility to mammary carcinogenesis using both animal and in vitro model systems. Studies in the rat model have included analysis of oncogene activation, mechanisms of signal transduction, and genetic linkage analysis to identify mammary tumor suppressor genes. He has also used toxicogenomics to dissect mechanisms of mechanism carcinogenesis, tumor progression and chemoprevention.  His studies in the area of toxicogenomics include the development and application of standards for DNA microarray experiments, and phenotypic anchoring of response of human cells, model organisms (yeast) and target organs (rodents) to toxicants, providing insights into dose and temporal responses, as well as mechanisms of action. He is also actively involved in technology development, including his patented work on RNAi and its application to the development of novel platforms for functional genomics (with Engineering Arts, Inc.). 

Selected Publications

Ren X, Zhang X, Kim AS, Mikheev AM, Fang M, Sullivan RC, Bumgarner RE, Zarbl H. (2008)
Comparative genomics of susceptibility to mammary carcinogenesis among inbred rat strains: role of reduced prolactin signaling in resistance of the Copenhagen strain. Carcinogenesis. 29(1):177-85.

Zarbl H. (2007) Toxicogenomic analyses of genetic susceptibility to mammary gland carcinogenesis in rodents: implications for human breast cancer. Breast Dis. 28:87-105.

Members of the Toxicogenomics Research Consortium. (2007) Multicenter study of acetaminophen hepatotoxicity reveals the importance of biological endpoints in genomic analyses. Toxicol Sci. 99(1):326-37.

Olsavsky KM, Page JL, Johnson MC, Zarbl H, Strom SC, Omiecinski CJ. (2007) Gene expression profiling and differentiation assessment in primary human hepatocyte cultures, established hepatoma cell lines, and human liver tissues. Toxicol Appl Pharmacol. 222(1):42-56.

Mikheev AM, Mikheeva SA, Rostomily R, Zarbl H. (2007) Dickkopf-1 activates cell death in MDA-MB435 melanoma cells. Biochem Biophys Res Commun. 352(3):675-80.

Ricicki EM, Luo W, Fan W, Zhao LP, Zarbl H, Vouros P. (2006) Quantification of N-(deoxyguanosin-8-yl)-4-aminobiphenyl adducts in human lymphoblastoid TK6 cells dosed with N-hydroxy-4-acetylaminobiphenyl and their relationship to mutation, toxicity, and gene expression profiling. Anal Chem. 78(18):6422-32.

Sudo H, Li-Sucholeiki XC, Marcelino LA, Gruhl AN, Zarbl H, Willey JC, Thilly WG. (2006) Distributions of five common point mutants in the human tracheal-bronchial epithelium.
Mutat Res. 596(1-2):113-27.

Guo, Y., Breeden, L. L., Kelley, E., and Eaton, D. L., and Zarbl, H. (2006). Analysis of cellular responses to Aflatoxin B1 in yeast expressing human Cytochrome P450 1A2 using cDNA microarrays. Mutation Research 593:121-142.

Bahramian, B. and Zarbl, H. (2005). Gene impedance: A natural process for control of gene expression and the origin of RNA interference. Journal of Theoretical Biology 233(3): 301-314. Erratum: Vol 236(1):1.

Luo, W., Fan, W., Xie, H., Jing, L., Ricicki, E., Vouros, P, Zhao, L.P., and Zarbl, H. (2005). Phenotypic anchoring of global gene expression profiles induced by N-hydroxy-4-acetylaminobiphenyl and Benzo(a)pyrene diol epoxide reveals correlations between expression profiles and mechanism of toxicity. Chemical Research in Toxicology 18(4): 619-629.

Bammler, T., R.P. Beyer, S. Bhattacharya, G. Boorman, A. Boyles, B.U. Bradford, R.E. Bumgarner, P.R. Bushel, D. Choi, M. Cunningham, S. Deng, H.K. Dressman, R.D. Fannin, F.M. Farin, J.H. Freedman, R.C. Fry, M.C., Humble, P. Hurban, L. Jing, T.J. Kavanagh W.K. Kaufmann, K.F. Kerr, S. Milton, J.A. Lapidus, M. Lasarev, J. Li, Y.-J. Li E.K. Lobenhofer, X. Lu, R.L. Malek, S. Milton, S. Nagalla, J.P. O’Malley, V.S. Palmer, P. Pattee, R.S. Paules, C.M. Perou, L. Qin, S.D. Quigley, M. Rodland, I. Rusyn, L.D. Samson, D.A. Schwartz, Y. Shi, J.-L. Shin, S.O. Sieber, S. Slifer, M.C. Speer, P.S. Spencer, D.I. Sproles, W.A. Suk, R.C. Sullivan, J. Swenberg, R. Tennant, R. Tian, S.A. Todd, C.J. Tucker, B. van Houten, B.K. Weis, H. Zarbl. (2005). Standardizing Global Gene Expression Analysis Between Laboratories and Across Platforms. Nature Methods 2:351 – 356.

Mikheev, A.M., Mikheeva S.A., Liu, B., Cohen, P. and Zarbl, H. (2003). A functional genomics approach for identification of putative tumor suppressor genes: Insulin Growth Factor Binding Protein-3 and Dickkopf-1 as suppressors of HeLa cell transformation. Carcinogenesis 24 (10): 1-13.

Mikheev, A., Mikheev, S., Inoiue, A., Leanderson, T., Jing, L., Zarbl, H. (2004). Frequent overexpression of CArG binding factor A (CBF-A) in rat mammary tumors. Breast Cancer Research and Treatment 88 (1): 95-102.