University of Wisconsin School of Medicine and Public Health McArdle Lab home

William F. Dove, Ph.D.

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BillDove George Streisinger Professor of Experimental Biology
Professor of Oncology and Medical Genetics

A.B., 1958, Chemistry, Amherst College, Massachusetts
Ph.D., 1962, Chemistry, California Institute of Technology
Postdoctoral research: Cambridge University; Stanford University

Office: 313A McArdle Laboratory
Telephone: Office - (608) 262-4977; Lab - (608) 262-0982
Email: dove@oncology.wisc.edu

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Research Interests: Colon cancer

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.

Selected recent publications

Kwong, L. N., and Dove, W. F.  APC and Its Modifiers in Colon Cancer, 24 pp.  In:  I. S. Nathke and B. M. McCartney (Eds.), APC Proteins.  Austin:  Landes Bioscience, 2009.

Bilger, A., Sullivan, R., Prunuske, A. J., Clipson, L., Drinkwater, N., and Dove, W. F.  Widespread Hyperplasia Induced by Transgenic TGFα in ApcMin Mice Is Associated with Only Regional Effects on Tumorigenesis.  Carcinogenesis, 29:  1825-1830, 2008.

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.

Chen, X., Halberg, R. B., Burch, R. P., and Dove, W. F.  Intestinal Adenomagenesis Involves Core Molecular Signatures of the Epithelial-Mesenchymal Transition.  J. Mol. Histol., 39: 283-294, 2008.

Durkee, B. Y., Mudd, S. R., Roen, C. N., Clipson, L., Newton, M. A., Weichert, J. P., Pickhardt, P. J., and Halberg, R. B.  Reproducibility of Tumor Volume Measurement at MicroCT Colonography in Living Mice.  Acad. Radiol., 15:  334-341, 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.

Kwong, L. N., Weiss, K. R., Haigis, K. M., and Dove, W. F.  Atm Is a Negative Regulator of Intestinal Neoplasia.  Oncogene, 27: 1013-1018, 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.

Halberg, R. B., and Dove, W. F.  Polyclonal Tumors in the Mammalian Intestine:  Are Interactions Among Multiple Initiated Clones Necessary for Tumor Initiation, Growth, and Progression?  Cell Cycle, 6:  44-51, 2007.

Kaiser, S., Park, Y.-K., Franklin, J. L., Halberg, R. B., Yu, M., Jessen, W. J., Freudenberg, J., Chen, X., Haigis, K., Jegga, A. G., Kong, S., Sakthivel, B., Xu, H., Reichling, T., Azhar, M., Boivin, G. P., Roberts, R. B., Bissahoyo, A. C., Gonzales, F., Bloom, G. C., Eschrich, S., Carter, S. L., Aronow, J. E., Kleimeyer, J., Kleimeyer, M., Ramaswamy, V., Settle, S. H., Boone, B., Levy, S., Graff, J. M., Doetschman, T., Groden, J., Dove, W. F., Threadgill, D. W., Yeatman, T. J., Coffey, R. J. Jr., and Aronow, B. J.  Transcriptional Recapitulation and Subversion of Embryonic Colon Development by Mouse Colon Tumor Models and Human Colon Cancer.  Genome Biol., 8:R131, 2007.

Kwong, L. N., Shedlovsky, A., Biehl, B. S., Clipson, L., Pasch, C. A., and Dove, W. F.  Identification of Mom7, a Novel Modifier of ApcMin/+  on Mouse Chromosome 18.  Genetics, 176: 1237-1244, 2007.

Megid, W. A., Ensenberger, M. G., Halberg, R. B., Stanhope, S. A., Kent-First, M. G., Prolla, T. A., and Bacher, J. W.  A Novel Method for Biodosimetry.  Radiat. Environ. Biophys., 46:  147-154, 2007.

Newton, M. A., Clipson, L., Thliveris, A. T., and Halberg, R. B.  A Statistical Test of the Hypothesis that Polyclonal Intestinal Tumors Arise by Random Collision of Initiated Clones.  Biometrics, 62:  721-727, 2006.

Wilkins, A. S., and Dove, W. F.  Human Biology:  An Ever-expanding Subject.  BioEssays, 28:  1146-1149, 2006.

Bacher, J. W., Abdel Megid, W. M., Kent-First, M. G., and Halberg, R. B.  Use of Mononucleotide Repeat Markers for Detection of Microsatellite Instability in Mouse Tumors.  Mol. Carcinog., 44:  285-292, 2005.

Leedham, S. J., Schier, S., Thliveris, A. T., Halberg, R. B., Newton, M. A., and Wright, N. A.  From Gene Mutations to Tumours – Stem Cells in Gastrointestinal Carcinogenesis.  Cell Prolif., 38:  387-405, 2005.

Leedham, S. J., Thliveris, A. T., Halberg, R. B., Newton, M. A., and Wright, N. A.  Gastrointestinal Stem Cells and Cancer – Bridging the Molecular Gap.  Stem Cell Rev., 1:  233-241, 2005.

Pickhardt, P. J., Halberg, R. B., Taylor, A. J., Durkee, B. Y., Fine, J., Lee, F. T., Jr., and Weichert, J. P. Microcomputed Tomography Colonography for Polyp Detection in an in Vivo Mouse Tumor Model. Proc. Natl. Acad. Sci. USA, 102: 3419-3422, 2005.

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.

Austin, C. P., Battey, J. F., Bradley, A., Bucan, M., Capecchi, M., Collins, F. S., Dove, W. F., Duyk, G., Dymecki, S., Eppig, J. T., Grieder, F. B., Heintz, N., Hicks, G., Insel, T. R., Joyner, A., Koller, B. H., Lloyd, K. C. K., Magnuson, T., Moore, M. W., Nagy, A., Pollock, J. D., Roses, A. D., Sands, A. T., Seed, B., Skarnes, W. C., Snoddy, J., Soriano, P., Stewart, D. J., Stewart, F., Stillman, B., Varmus, H., Varticovski, L., Verma, I. M., Vogt, T. F., von Melchner, H., Witkowski, J., Woychik, R. P., Wurst, W., Yancopoulos, G. D., Young, S. G., and Zambrowicz, B. The Knockout Mouse Project. Nat. Genet., 36: 921-924, 2004.

Haigis, K. M., Hoff, P. D., White, A., Shoemaker, A. R., Halberg, R. B., and Dove, W. F. Tumor Regionality in the Mouse Intestine Reflects the Mechanism of Loss of Apc Function. Proc. Natl. Acad. Sci. USA, 101: 9769-9773, 2004.

Boivin, G. P., Washington, K., Yang, K., Ward, J. M., Pretlow, T. P., Russell, R., Besselsen, D. G., Godfrey, V. L., Doetschman, T., Dove, W. F., Pitot, H. C., Halberg, R. B., Itzkowitz, S. H., Groden, J., and Coffey, R. J. Pathology of Mouse Models of Intestinal Cancer: Consensus Report and Recommendations. Gastroenterology, 124: 762-777, 2003.

Chen, X., Halberg, R. B., Ehrhardt, W. M., Torrealba, J., and Dove, W. F. Clusterin as a Biomarker in Murine and Human Intestinal Neoplasia. Proc. Natl. Acad. Sci. USA, 100: 9530-9535, 2003.

Dove, W. Aurora and the Hunt for Cancer-modifying Genes. Nat. Genet., 34: 353-354, 2003.

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.

Haigis, K. M., Caya, J. G., Reichelderfer, M., and Dove, W. F. Intestinal Adenomas Can Develop with a Stable Karyotype and Stable Microsatellites. Proc. Natl. Acad. Sci. USA, 99: 8927-8931, 2002.

Hoff, P. D., Halberg, R. B., Shedlovsky, A., Dove, W. F., and Newton, M. A. Identifying Carriers of a Genetic Modifier Using Nonparametric Bayesian Methods. In: C. Gatsonis, R. E. Kass, B. Carlin, A. Carriquiry, A. Gelman, I. Verdinelli, and M. West (Eds.), Lecture Notes in Statistics, Vol. 162 (Series): Case Studies in Bayesian Statistics, Vol. 5, pp. 329-343. New York: Springer-Verlag, 2002.

Cormier, R. T., and Dove, W. F. Dnmt1N/+ Reduces the Net Growth Rate and Multiplicity of Intestinal Adenomas in C57BL/6-Multiple Intestinal Neoplasia (Min)/+ Mice Independently of p53 but Demonstrates Strong Synergy with the Modifier of Min 1AKR Resistance Allele. Cancer Res., 60: 3965-3970, 2000.

Cormier, R. T., Bilger, A., Lillich, A. J., Halberg, R. B., Hong, K. H., Gould, K. A., Borenstein, N., Lander, E. S., and Dove, W. F. The Mom1AKR Intestinal Tumor Resistance Region Consists of Pla2g2a and a Locus Distal to D4Mit64. Oncogene, 19: 3182-3192, 2000.

Crow, J. F., and Dove, W. F. (Eds.) Perspectives on Genetics. Madison, WI: The University of Wisconsin Press, 2000. (723 pp.)

Dove, W. F. Closing the Circle: AD Hershey and Lambda I. In: F. W. Stahl (Ed.), We Can Sleep Later: Alfred D. Hershey and the Origins of Molecular Biology, Cold Spring Harbor: Cold Spring Harbor Laboratory Press, 2000.

Dove, W. F. Genes and Cancer: Risk Determinants and Agents of Change. In: M. D. Abeloff, J. O. Armitage, A. S. Lichter, and J. E. Niederhuber (Eds.), Clinical Oncology, Second Edition, Chap. 4, pp. 54-76. New York: Churchill Livingstone, 2000.

Dove, W. F., Halberg, R. B., Clipson, L., and Riegel, I. L. Techniques for Modeling Human Intestinal Cancer in Mice. The Jackson Laboratory, October 2000. http://emice.nci.nih.gov/emice/contentfiles/emicePublicLFS/section2.doc

Halberg, R. B., Katzung, D. S., Hoff, P. D., Moser, A. R., Cole, C. E., Lubet, R. A., Donehower, L. A., Jacoby, R. F., and Dove, W. F. Tumorigenesis in the Multiple Intestinal Neoplasia Mouse: Redundancy of Negative Regulators and Specificity of Modifiers. Proc. Natl. Acad. Sci. USA, 97: 3461-3466, 2000.

Shoemaker, A. R., Haigis, K. M., Baker, S. M., Dudley, S., Liskay, R. M., and Dove, W. F. Mlh1 Deficiency Enhances Several Phenotypes of ApcMin/+ Mice. Oncogene, 19: 2774-2779, 2000.

Bailey, J., Cook, L. J., Kilmer-Barber, R., Swanston, E., Solnica-Krezel, L., Lohman, K., Dove, W. F., Dee, J., and Anderson, R. W. Identification of Three Genes Expressed Primarily during Development in Physarum polycephalum. Arch. Microbiol., 172: 364-376, 1999.

Battey, J., Jordan, E., Cox, D., and Dove, W. An Action Plan for Mouse Genomics. Nature Genetics, 21: 73-75, 1999.

Cox, R. D., Hugill, A., Shedlovsky, A., Noveroske, J. K., Best, S., Justice, M. J., Lehrach, H., and Dove, W. F. Contrasting Effects of ENU Induced Embryonic Lethal Mutations of the quaking Gene. Genomics, 57: 333-341, 1999.

Crow, J. W., and Dove, W. F. Bird's Eye View - a Decade of Perspectives. Genetics, 148: 1405-1407, 1998.

Dove, W. F., Cormier, R. T., Gould, K. A., Halberg, R. B., Merritt, A. J., Newton, M. A., and Shoemaker, A. R. The Intestinal Epithelium and Its Neoplasms: Genetic, Cellular and Tissue Interactions. Phil. Trans. R. Soc., Lond. B., 353: 915-923, 1998.

Gould, K. A., and Dove, W. F. Analysis of the Mom1 Modifier of Intestinal Neoplasia in Mice. Exp. Lung Res., 24: 437-453, 1998.

Shoemaker, A. R., Moser, A. R., Midgley, C. A., Clipson, L., Newton, M. A., and Dove, W. F. A Resistant Genetic Background Leading to Incomplete Penetrance of Intestinal Neoplasia and Reduced Loss of Heterozygosity in ApcMin/+ Mice. Proc. Natl. Acad. Sci. USA, 95: 10826-10831, 1998.

Cormier, R.T., Hong, K.H., Halberg, R.B., Hawkins, T.L., Richardson, P., Mulherkar, R., Dove, W.F., and Lander, E.S. Secretory Phospholipase Pla2g2a Confers Resistance to Intestinal Tumorigenesis. Nature Genet., 17: 88-91, 1997.

Gould, K.A., and Dove, W.F. Localized Gene Action Controlling Intestinal Neoplasia in Mice. Proc. Natl. Acad. Sci. USA, 94: 5848-5853, 1997.

Merritt, A.J., Gould, K.A., and Dove, W.F. Polyclonal Structure of Intestinal Adenomas in ApcMin/+ Mice with Concomitant Loss of Apc+ from all Tumor Lineages. Proc. Natl. Acad. Sci. USA, 94: 13927-13931, 1997.

Shoemaker, A.R., Gould, K.A., Luongo, C., Moser, A.R., and Dove, W. F. Studies of Neoplasia in the Min Mouse. BBA Reviews on Cancer, 1332: F25-F48, 1997.

Dietrich, W.F., Lander, E.S., Smith, J.S., Moser, A.R., Gould, K.A., Luongo, C., Borenstein, N., and Dove, W. Genetic Identification of Mom-1, a Major Modifier Locus Affecting Min-induced Intestinal Neoplasia in the Mouse. Cell, 75: 631-639, 1993.