A.B., 1958, Chemistry, Amherst College, Massachusetts
Ph.D., 1962, Chemistry, California Institute of Technology
Postdoctoral research: Cambridge University; Stanford University
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.
Pleiman JK, Irving AA, Wang Z, Toraason E, Clipson L, Dove WF, Deming DA, Newton MA. The conserved protective cyclic AMP-phosphodiesterase function PDE4B is expressed in the adenoma and adjacent normal colonic epithelium of mammals and silenced in colorectal cancer. PLoS Genet. 2018 Sep 6;14(9):e1007611. doi: 10.1371/journal.pgen.1007611. [Epub ahead of print] PubMed PMID: 30188895.
Dove WF. Weaving a Tapestry from Threads Spun by Geneticists: The Series Perspectives on Genetics, 1987-2008. Genetics. 2016 Jul;203(3):1011-22. doi: 10.1534/genetics.116.191155. PubMed PMID: 27384024; PubMed Central PMCID: PMC4937473.
Sievers CK, Leystra AA, Clipson L, Dove WF, Halberg RB. Understanding intratumoral heterogeneity: lessons from the sequence analysis of at-risk tissue and pre-malignant lesions in the colon. Cancer Prev Res (Phila). 2016 May 19. pii: canprevres.0096.2016. [Epub ahead of print] PubMed PMID: 27199343; PubMed Central PMCID: PMC4970935.
Irving AA, Plum LA, Blaser WJ, Ford MR, Weng C, Clipson L, DeLuca HF, Dove WF. Cholecalciferol or 25-hydroxycholecalciferol neither prevents nor treats adenomas in a rat model of familial colon cancer. J Nutr. 2015 Feb;145(2):291-8. doi: 10.3945/jn.114.204396. Epub 2014 Dec 24. PubMed PMID: 25644350; PubMed Central PMCID: PMC4304025.
Amos-Landgraf, J. M., Heijmans, J., Wielenga, M. C. B., Dunkin, E., Krentz, K. J., Clipson, L. Ederveen, A. G., Groothuis, P. G., Mosselman, S., Muncan, V., Hommes, D. W., Shedlovsky, A., Dove, W. F., and van den Brink, G. R. Sex Disparity in Colonic Adenomagenesis Involves Promotion by Male Hormones, Not Protection by Female Hormones. Proc. Natl. Acad. Sci. USA, 111(46): 16514-16519, 2014.
Dove, W., and Shedlovsky, A. François Jacob – The Rest of the Story. Res. Microbiol., 165(5): 362-364, 2014.
Dove, W. F., Shedlovsky, A., Clipson, L., Amos-Landgraf, J. M., Halberg, R. B., Krentz, K. J., Boehm, F. J., Newton, M. A., Adams, D. J., and Keane, T. M. A Strategy to Identify Dominant Point Mutant Modifiers of a Quantitative Trait. G3 (Bethesda), 4(6): 1113-1121, 2014.
Irving, A. A., Yoshimi, K., Hart, M. L., Parker, T., Clipson, L., Ford, M. R., Kuramoto, T., Dove, W. F., and Amos-Landgraf, J. M. The Utility of Apc-Mutant Rats in Modeling Human Colon Cancer. Dis. Model. Mech., 7(11): 1215-1225, 2014.
Irving, A. A., Young, L. B., Pleiman, J. K., Konrath, M. J., Marzella, B., Nonte, M., Cacciatore, J., Ford, M. R., Clipson, L., Amos-Landgraf, J. M., and Dove, W. F. A Simple, Quantitative Method Using Alginate Gel to Determine Rat Colonic Tumor Volume In Vivo. Comp. Med., 64(2): 128-134, 2014.
Ivancic, M. M., Irving, A. A., Jonakin, K. G., Dove, W. F., and Sussman, M. R. The Concentrations of EGFR, LRG1, ITIH4, and F5 in Serum Correlate with the Number of Colonic Adenomas in ApcPirc/+ Rats. Cancer Prev. Res., 7(11): 1160-1169, 2014.
Dove, W., and Shedlovsky, A. From MRC-Cambridge to Madison, Wisconsin. In: Memories and Consequences: Visiting Scientists at the MRC Laboratory of Molecular Biology, Cambridge. Cambridge, UK: Medical Research Council, 2013.
Ivancic, M. M., Huttlin, E. L., Chen, X., Pleiman, J. K., Irving, A. A., Hegeman, A. D., Dove, W. F., and Sussman, M. R. Candidate Serum Biomarkers for Early Intestinal Cancer Using 15N Metabolic Labeling and Quantitative Proteomics in the ApcMin/+ Mouse. J. Proteome Res., 12(9): 4152-4166, 2013.
Pickhardt, P. J., Kim, D. H., Pooler, B. D., Hinshaw, J. L., Barlow, D., Jensen, D., Reichelderfer, M., and Cash, B. D. Assessment of Volumetric Growth Rates of Small Colorectal Polyps with CT Colonography: a Longitudinal Study of Natural History. Lancet Oncol., 14(8): 711-720, 2013.
Thliveris, A. T., Schwefel, B., Clipson, L., Plesh, L., Zahm, C. D., Leystra, A. A., Washington, M. K., Sullivan, R., Deming, D. A., Newton, M. A., and Halberg, R. B. Transformation of Epithelial Cells through Recruitment Leads to Polyclonal Intestinal Tumors. Proc. Natl. Acad. Sci. USA, 110(28): 11523-11528, 2013.
Washington, M. K., Powell, A. E., Sullivan, R., Sundberg, J. P., Wright, N., Coffey, R. J., and Dove, W. F. Pathology of Rodent Models of Intestinal Cancer: Progress Report and Recommendations. Gastroenterology, 144(4): 705-717, 2013.
Amos-Landgraf, J. M., Clipson, L., Newton, M. A., and Dove, W. F. The Many Ways to Open the Gate to Colon Cancer. Cell Cycle, 11: 1261-1262, 2012.
Amos-Landgraf, J. M., Irving, A. A., Hartman, C., Hunter, A., Laube, B., Chen, X., Clipson, L., Newton, M. A., and Dove, W. F. Monoallelic Silencing and Haploinsufficiency in Early Murine Intestinal Neoplasms. Proc. Natl. Acad. Sci. USA, 109: 2060-2065, 2012.
Dove, W., and Susman, M. Retrospective. James F. Crow (1916-2012). Science, 335: 812, 2012.
Thliveris, A. T., Clipson, L., Sommer, L. L., Schoenike, B. A., Hasenstein, J. R., Schlamp, C. L., Alexander, C. M., Newton, M. A., Dove, W. F., and Amos-Landgraf, J. M. Regulated Expression of Chromobox Homolog 5 Revealed in Tumors of ApcMin/+ ROSA11 Gene Trap Mice. G3 (Bethesda), 2: 569-578, 2012.