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

James D. Shull, Ph.D.

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Shull Centennial Professor and Chairman, Department of Oncology
Director, McArdle Laboratory
Associate Director for Basic Research, UW Carbone Cancer Center


B.S., 1975, Zoology, University of Nebraska-Lincoln
M.S., 1977, Microbiology and Immunology, University of Nebraska-Lincoln
Ph.D., 1984, Biochemistry, University of Wisconsin-Madison
Postdoctoral research: Oncology, University of Wisconsin-Madison

Office: 708 McArdle Laboratory
Telephone: Office - (608) 265-5003; Lab - (608) 262-9821
Email: shull@oncology.wisc.edu


Research Interests: cancer genetics, hormones and breast cancer, estrogen action

Research Description: Estrogens are inextricably implicated in the etiology of breast cancer.  The primary goals of our research group are to utilize the ACI rat model of 17β-estradiol (E2)-induced mammary cancer to identify novel genetic determinants of breast cancer susceptibility and to define the molecular mechanisms through which estrogens contribute to development of breast cancer. Whereas ACI rats are highly and uniquely susceptible to E2-induced mammary cancer, the Copenhagen (COP) and Brown Norway (BN) rat strains are resistant to mammary cancer development when treated with E2.  In genetic crosses between ACI and COP or BN rats, we have mapped several genetic determinants of mammary cancer susceptibility within the rat genome, designated Emca1 through Emca9. Research currently underway is focused on high resolution mapping and identification of the mammary cancer susceptibility genes that reside within these Emca loci.  We hope to then determine how these genes influence mammary cancer development and to evaluate the impact of these same genes on breast cancer risk in human populations.  Knowledge regarding the identities of these genes should reveal novel insight into the mechanisms through which estrogens contribute to breast cancer development.

Mammary cancers that develop in E2 treated ACI rats exhibit non-random and recurring patterns of chromosome copy number changes.  A second project underway in our group is focused on defining the role of genome instability in the genesis of E2-induced mammary cancer. We also hope to define the mechanism through which E2 induces genome instability in this rat model.

Selected recent publications

Aitman, T. J., Critser, J. K., Cuppen, E., Dominiczak, A., Fernandez-Suarez, X. M., Flint, J., Gauguier, D., Geurts, A. M., Gould, M., Harris, P. C., Holmdahl, R., Hubner, N., Izsvák, Z., Jacob, H. J., Kuramoto, T., Kwitek, A. E., Marrone, A., Mashimo, T., Moreno, C., Mullins, J., Mullins, L., Olsson, T., Pravenec, M., Riley, L., Saar, K., Serikawa, T., Shull, J. D., Szpirer, C., Twigger, S. N., Voigt, B., and Worley, K.  Progress and Prospects in Rat Genetics:  A Community View.  Nat. Genet., 40:  516-522, 2008.

Guryev, V., Saar, K., Adamovic, T., Verheul, M., van Heesch, S. A. A. C., Cook, S., Pravenec, M., Aitman, T., Jacob, H., Shull, J. D., Hubner, N., and Cuppen, E.  Distribution and Functional Impact of DNA Copy Number Variation in the Rat.  Nat. Genet., 40:  538-545, 2008.

Kurz, S. G., Hansen, K. K., McLaughlin, M. T., Shivaswamy, V., Schaffer, B. S., Gould, K. A., McComb, R. D., Meza, J. L., and Shull, J. D.  Tissue-Specific Actions of the Ept1, Ept2, Ept6, and Ept9 Genetic Determinants of Responsiveness to Estrogens in the Female Rat.  Endocrinology, 149:  3850-3859, 2008.

Ruhlen, R. L., Willbrand, D. M., Besch-Williford, C. L., Ma, L., Shull, J. D., and Sauter, E. R.  Tamoxifen Induces Regression of Estradiol-Induced Mammary Cancer in the ACI.COP-Ept2 Rat Model.  Breast Cancer Res. Treat., in press, 2008 [Epub ahead of print Sep 9 2008].

Adamovic, T., Roshani, L., Chen, L., Schaffer, B. S., Helou, K., Levan, G., Olsson, B., and Shull, J. D.  Nonrandom Pattern of Chromosome Aberrations in 17β-Estradiol-Induced Rat Mammary Tumors:  Indications of Distinct Pathways for Tumor Development.  Genes Chromosomes Cancer, 46:  459-469, 2007.

Shull, J. D.  The Rat Oncogenome:  Comparative Genetics and Genomics of Rat Models of Mammary Carcinogenesis.  Breast Dis., 28:  69-86, 2007.

Shull, J. D., Lachel, C. M., Murrin, C. R., Pennington, K. L., Schaffer, B. S., Strecker, T. E., and Gould, K. A.  Genetic Control of Estrogen Action in the Rat:  Mapping of QTLs That Impact Pituitary Lactotroph Hyperplasia in a BN x ACI Intercross.  Mamm. Genome, 18:  657-669, 2007.

Gould, K. A., Strecker, T. E., Hansen, K. K., Bynoté, K. K., Peterson, K. A., and Shull, J. D.  Genetic Mapping of Loci Controlling Diethylstilbestrol-Induced Thymic Atrophy in the Brown Norway Rat.  Mamm. Genome, 17:  451-464, 2006.

Schaffer, B. S., Lachel, C. M., Pennington, K. L., Murrin, C. R., Strecker, T. E., Tochacek, M., Gould, K. A., Meza, J. L., McComb, R. D., and Shull, J. D.  Genetic Bases of Estrogen-Induced Tumorigenesis in the Rat: Mapping of Loci Controlling Susceptibility to Mammary Cancer in a Brown Norway x ACI Intercross.  Cancer Res., 66:  7793-7800, 2006.

Shull, J. D., Lachel, C. M., Strecker, T. E., Spady, T. J., Tochacek, M., Pennington, K. L., Murrin, C. R., Meza, J. L., Schaffer, B. S., Flood, L. A., and Gould, K. A.  Genetic Bases of Renal Agenesis in the ACI Rat: Mapping of Renag1 to Chromosome 14.  Mamm. Genome, 17:  751-759, 2006.

Gould, K. A., Pandey, J., Lachel, C. M., Murrin, C. R., Flood, L. A., Pennington, K. L., Schaffer, B. S., Tochacek, M., McComb, R. D., Meza, J. L., Wendell, D. L., and Shull, J. D.  Genetic Mapping of Eutr1, a Locus Controlling E2-Induced Pyometritis in the Brown Norway Rat, to RNO5.  Mamm. Genome, 16:  854-864, 2005.

Pandey, J., Gould, K. A., McComb, R. D., Shull, J. D., and Wendell, D. L.  Localization of Eutr2, a Locus Controlling Susceptibility to DES-Induced Uterine Inflammation and Pyometritis, to RNO5 Using a Congenic Rat Strain.  Mamm. Genome, 16:  865-872, 2005.

Strecker, T. E., Spady, T. J., Schaffer, B. S., Gould, K. A., Kaufman, A. E., Shen, F., McLaughlin, M. T., Pennington, K. L., Meza, J. L., and Shull, J. D.  Genetic Bases of Estrogen-Induced Pituitary Tumorigenesis: Identification of Genetic Loci Determining Estrogen-Induced Pituitary Growth in Reciprocal Crosses Between the ACI and Copenhagen Rat Strains.  Genetics, 169:  2189-2197, 2005.

Gould, K. A., Tochacek, M., Schaffer, B. S., Reindl, T. M., Murrin, C. R., Lachel, C. M., VanderWoude, E. A., Pennington, K. L., Flood, L. A., Bynote, K. K., Meza, J. L., Newton, M. A., and Shull, J. D.  Genetic Determination of Susceptibility to Estrogen-Induced Mammary Cancer in the ACI Rat:  Mapping of Emca1 and Emca2 to Chromosomes 5 and 18.  Genetics, 168:  2113-2125, 2004.