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Research Interests: Genetics and molecular biology of carcinogenesis

Research Description: Genetic factors can play an important role in determining an individual's risk for developing cancer. We are studying inbred strains of mice that are highly sensitive to tumor induction in specific tissues as a model for understanding the mechanism of action of cancer susceptibility genes. In many cases, these genes also play an important role in regulating the proliferation or differentiation of normal cells. We are currently attempting to determine the molecular identities of several cancer susceptibility genes using a "reverse genetic" approach, based on first mapping the genes and then using this positional information as starting points for molecular cloning.

Selected recent publications

Attia, S., Holen, K. D., Thomas, J. P., Richie, K., Dzelak, T., Teeter, K., Warren, D., Bilger, A., Fine, J., Eickhoff, J., Drinkwater, N., Mulkerin, D., and Morgan-Meadows, S.  Biologic Study of the Effects of Octreotide-LAR on Growth Hormone in Unresectable and Metastatic Hepatocellular Carcinoma.  Clin. Adv. Hematol. Oncol., 6:  44-54, 2008.

Bilger, A., Sullivan, R., Prunuske, A. J., Clipson, L., Drinkwater, N., and Dove, W. F.  Widespread Hyperplasia Induced by Transgenic TGFa in Apc^Min Mice Is Associated with Only Regional Effects on Tumorigenesis.  Carcinogenesis, in press, 2008 [Epub ahead of print Feb 28 2008].

Drew, J. C., Kastenmeier, A. S., and Drinkwater, N. R.  Ancestral Bias in the Hras1 Gene and Distal Chromosome 7 Among Inbred Mice.  Mamm. Genome, 18:  732-738, 2007.

Thomae, T. L., Stevens, E. A., Liss, A. L., Drinkwater, N. R., and Bradfield, C. A. The Teratogenic Sensitivity to 2,3,7,8-Tetrachlorodibenzo-p-dioxin Is Modified by a Locus on Mouse Chromosome 3. Mol. Pharmacol., 69: 770-775, 2006.

Bilger, A., Bennett, L. M., Carabeo, R. A., Chiaverotti, T. A., Dvorak, C., Liss, K. M., Schadewald, S. A., Pitot, H. C., and Drinkwater, N. R. A Potent Modifier of Liver Cancer Risk on Distal Mouse Chromosome 1: Linkage Analysis and Characterization of Congenic Lines. Genetics, 167: 859-866, 2004.

Kelley, M. R., Tompkinson, A. E., Williams, K. J., Drinkwater, N. R., and Fung, V. A. Frontiers of Mutagenesis and DNA Repair: A Workshop. Cancer Res., 64: 3357-3360, 2004.

Yao, G., Craven, M., Drinkwater, N., and Bradfield, C. A. Interaction Networks in Yeast Define and Enumerate the Signaling Steps of the Vertebrate Aryl Hydrocarbon Receptor. PLoS Biol., 2: E65, 2004.

Bugni, J. M., and Drinkwater, N. R. Representational Difference Analysis of Gene Expression. In: W. S. El-Deiry (Ed.), Methods in Molecular Biology, Vol. 222: Tumor Suppressor Genes: Pathways and Isolation Strategies, Chap. 24, pp. 385-397. Totowa, NJ: Humana Press Inc., 2003.

Chiaverotti, T. A., and Drinkwater, N. R. C57BR/cdJ Hepatocarcinogen Susceptibility Genes Act Cell-Autonomously in C57BR/cdJ C57BL/6J Chimeras. Cancer Res., 63: 4914-4919, 2003.

Thomas, R. S., Rank, D. R., Penn, S. G., Craven, M. W., Drinkwater, N. R., and Bradfield, C. A. Developing Toxicologically Predictive Gene Sets Using cDNA Microarrays and Bayesian Classification. Methods Enzymol., 357: 198-205, 2002.

Bugni, J. M., Poole, T. M., and Drinkwater, N. R. The little Mutation Suppresses DEN-induced Hepatocarcinogenesis in Mice and Abrogates Genetic and Hormonal Modulation of Susceptibility. Carcinogenesis, 22: 1853-1862, 2001.

Chiaverotti, T., Carabeo, R., and Drinkwater, N. Genetic and Hormonal Regulation of Murine Hepatocarcinogenesis. In: H. Hiai and O. Hino (Eds.), Animal Models of Cancer Predisposition Syndromes, Prog. Exp. Tumor Res., Vol. 35, pp. 131-142. Basel: Karger, 1999.

Dragan, Y. P., Poole, T. M., and Drinkwater, N. R. Hormonal Mechanisms in Liver Cancer. In: P. W. Harvey, K. C. Rush, and A. Cockburn (Eds.), Endocrine and Hormonal Toxicology, pp. 309-326. New York: John Wiley & Sons Ltd., 1999.

Griep, A. E., Krawcek, J., Lee, D., Albert. D. M., Carabeo, R., Drinkwater, N., McCall, M., Sattler, C., Lasudry, J., and Lambert, P. F. Multiple Genetic Loci Modify Risk for Retinoblastoma in Transgenic Mice. Invest. Ophthalmol. Vis. Sci., 39: 2723-2732, 1998.

Lee, G.-H., Bugni, J.M., Obata, M., Nishimori, H., Ogawa, K., and Drinkwater, N.R. Genetic Dissection of Susceptibility to Murine Ovarian Teratomas that Originate from Parthenogenetic Oocytes. Cancer Res., 57: 590-593, 1997.

Poole, T.M., and Drinkwater, N.R. Two Genes Abrogate the Inhibition of Murine Hepatocarcinogenesis by Ovarian Hormones. Proc. Natl. Acad. Sci. USA, 93: 5848-5853, 1996.

Lee, G.-H., Bennett, L.M., Carabeo, R.A., and Drinkwater, N.R. Identification of Hepatocarcinogen-Resistance Genes in DBA/2 Mice. Genetics, 139: 387-395, 1995.