William Dove

Research Description:
Our laboratory studies the genetic, cellular, and molecular interactions involved in cancer of the self-renewing mammalian intestinal epithelium. To pursue this goal, we have established two complementary animal models for familial colon cancer — the Min (Multiple intestinal neoplasia) mouse and Pirc (Polyposis in the rat colon) rat kindreds. By manipulating the genetic background of these kindreds, we can discover genes that quantitatively or qualitatively influence the colon cancer phenotype. The emergent power to analyze the genome, transcriptome, and proteome of the mouse, rat, and human connects these biological studies in experimental animals to the molecular players that control this disease in humans.

The power to phenotype the neoplastic process is greatly enhanced by achieving both spatial and temporal resolution. Spatial resolution by immunohistochemistry, in situ hybridization, or somatic lineage marking illuminates issues in cellular/genetic interactions involving the neoplastic lineage and the microenvironment. Imaging tumors over time in live animals by either optical endoscopy or virtual colonoscopy addresses issues in tumor progression and regression, spontaneous or induced by host factors, environmental agents, or drugs.

A doctoral or postdoctoral member of our laboratory would learn the biology of the laboratory mouse and rat, including the assay of molecular markers of neoplastic development by immunohistochemistry or in situ hybridization, objective assessment of neoplastic growth and regression, and investigation of the autonomy of gene action by tissue grafting, chimerism and mosaicism. Group members can broaden their research capacity through our ongoing research interactions with collaborators on campus. Working with biostatisticians, we become familiar with the genetics of quantitative modifiers of tumor susceptibility. Working with faculty in radiology and medical physics, we explore new imaging methods. With the Biotechnology Center, we engage the evolving power of mass spectrometry in the analysis of protein markers expressed in the plasma of tumor-bearing animals. Altogether, uniquely complementing other investigations worldwide, our Wisconsin team hopes to achieve a deep understanding of the biology of colon cancer and thereby to impact its management in humans through diagnosis, prognosis, and early detection.

Dr. Dove is no longer accepting graduate students.

Representative Publications:
Search PubMed for more publications by William Dove

Chen, X., Ehrhardt, W. M., Halberg, R. B., Aronow, B. J., and Dove, W. F. Cellular Expression Patterns of Genes Upregulated in Murine and Human Colonic Neoplasms. J. Histochem. Cytochem., 56: 433-441, 2008.

Halberg, R. B., Chen, X., Amos-Landgraf, J. M., White, A., Rasmussen, K., Clipson, L., Pasch, C., Sullivan, R., Pitot, H. C., and Dove, W. F. The Pleiotropic Phenotype of Apc Mutations in the Mouse: Allele Specificity and Effects of the Genetic Background. Genetics, 180: 601-609, 2008.

Amos-Landgraf, J. M., Kwong, L. N., Kendziorski, C. M., Reichelderfer, M., Torrealba, J., Weichert, J., Haag, J. D., Chen, K.-S., Waller, J. L., Gould, M. N., and Dove, W. F. A Target-selected Apc-mutant Rat Kindred Enhances the Modeling of Familial Human Colon Cancer. Proc. Natl. Acad. Sci. USA, 104: 4036-4041, 2007.

Thliveris, A. T., Halberg, R. B., Clipson, L., Dove, W. F., Sullivan, R., Washington , M. K., Stanhope, S., and Newton , M. A. Polyclonality of Familial Murine Adenomas: Analyses of Mouse Chimeras with Low Tumor Multiplicity Suggest Short-range Interactions. Proc. Natl. Acad. Sci. USA, 102: 6960-6965, 2005.

Haigis, K. M., and Dove, W. F. A Robertsonian Translocation Suppresses a Somatic Recombination Pathway to Loss of Heterozygosity. Nat. Genet., 33: 33-39, 2003.