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
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.
Ding L, Shunkwiler LB, Harper NW, Zhao Y, Hinohara K, Huh SJ, Ekram MB, Guz J, Kern MJ, Awgulewitsch A, Shull JD, Smits BMG, Polyak K. Deletion of Cdkn1b in ACI rats leads to increased proliferation and pregnancy-associated changes in the mammary gland due to perturbed systemic endocrine environment. PLoS Genet. 2019 Mar 20;15(3):e1008002. doi: 10.1371/journal.pgen.1008002. eCollection 2019 Mar. PubMed PMID: 30893315.
Dennison KL, Chack AC, Hickman MP, Harenda QE, Shull JD. Ept7, a quantitative trait locus that controls estrogen-induced pituitary lactotroph hyperplasia in rat, is orthologous to a locus in humans that has been associated with numerous cancer types and common diseases. PLoS One. 2018 Sep 27;13(9):e0204727. doi: 10.1371/journal.pone.0204727. eCollection 2018. PubMed PMID: 30261014; PubMed Central PMCID: PMC6160183
Jerry DJ, Shull JD, Hadsell DL, Rijnkels M, Dunphy KA, Schneider SS, Vandenberg LN, Majhi PD, Byrne C, Trentham-Dietz A. Genetic variation in sensitivity to estrogens and breast cancer risk. Mamm Genome. 2018 Feb;29(1-2):24-37. doi: 10.1007/s00335-018-9741-z. Epub 2018 Feb 27. PubMed PMID: 29487996; PubMed Central PMCID: PMC5936622.
Shull JD, Dennison KL, Chack AC, Trentham-Dietz A. Rat models of 17β-estradiol-induced mammary cancer reveal novel insights into breast cancer etiology and prevention. Physiol Genomics. 2018 Mar 1;50(3):215-234. doi: 10.1152/physiolgenomics.00105.2017. Epub 2018 Jan 26. PubMed PMID: 29373076; PubMed Central PMCID: PMC5899232.
Das Gupta S, Sae-Tan S, Wahler J, So JY, Bak MJ, Cheng LC, Lee MJ, Lin Y, Shih WJ, Shull JD, Safe S, Yang CS, Suh N. Dietary γ-Tocopherol-Rich Mixture Inhibits Estrogen-Induced Mammary Tumorigenesis by Modulating Estrogen Metabolism, Antioxidant Response, and PPARγ. Cancer Prev Res (Phila). 2015 Sep;8(9):807-16. doi: 10.1158/1940-6207.CAPR-15-0154. Epub 2015 Jun 30. PubMed PMID: 26130252; PubMed Central PMCID: PMC4560648.
Dennison KL, Samanas NB, Harenda QE, Hickman MP, Seiler NL, Ding L, Shull JD. Development and characterization of a novel rat model of estrogen-induced mammary cancer. Endocr Relat Cancer. 2015 Apr;22(2):239-48. doi: 10.1530/ERC-14-0539. PubMed PMID: 25800038; PubMed Central PMCID: PMC4372900.
Samanas NB, Commers TW, Dennison KL, Harenda QE, Kurz SG, Lachel CM, Wavrin KL, Bowler M, Nijman IJ, Guryev V, Cuppen E, Hubner N, Sullivan R, Vezina CM, Shull JD. Genetic etiology of renal agenesis: fine mapping of Renag1 and identification of Kit as the candidate functional gene. PLoS One. 2015 Feb 18;10(2):e0118147. doi: 10.1371/journal.pone.0118147. eCollection 2015. PubMed PMID: 25693193; PubMed Central PMCID: PMC4333340.
Colletti, J. A. II, Leland-Wavrin, K. M., Kurz, S. G., Hickman, M. P., Seiler, N. L., Samanas, N. B., Eckert, Q. A., Dennison, K. L., Ding, L., Schaffer, B. S., and Shull, J. D. Validation of Six Genetic Determinants of Susceptibility to Estrogen-Induced Mammary Cancer in the Rat and Assessment of Their Relevance to Breast Cancer Risk in Humans. G3 (Bethesda), 4(8): 1385-1394, 2014.
Flister, M. J., Endres, B. T., Rudemiller, N., Sarkis, A. B., Santarriaga, S., Roy, I., Lemke, A., Geurts, A. M., Moreno, C., Ran, S., Tsaih, S.-W., De Pons, J., Carlson, D. F., Tan, W., Fahrenkrug, S. C., Lazarova, Z., Lazar, J., North, P. E., LaViolette, P. S., Dwinell, M. B., Shull, J. D., and Jacob, H. J. CXM – A New Tool for Mapping Breast Cancer Risk in the Tumor Microenvironment. Cancer Res., 74(22): 6419-6429, 2014.
Kurz, S. G., Dennison, K. L., Samanas, N. B., Hickman, M. P., Eckert, Q. A., Walker, T. L., Cupp, A. S., and Shull, J. D. Ept7 Influences Estrogen Action in the Pituitary Gland and Body Weight of Rats. Mamm. Genome, 25(5-6): 244-252, 2014.
Ding, L., Zhao, Y., Warren, C. L., Sullivan, R., Eliceiri, K. W., and Shull, J. D. Association of Cellular and Molecular Responses in the Rat Mammary Gland to 17β-Estradiol with Susceptibility to Mammary Cancer. BMC Cancer, 13(1):573, 2013.
Schaffer, B. S., Leland-Wavrin, K. M., Kurz, S. G., Colletti, J. A., Seiler, N. L., Warren, C. L., and Shull, J. D. Mapping of Three Genetic Determinants of Susceptibility to Estrogen-Induced Mammary Cancer within the Emca8 Locus on Rat Chromosome 5. Cancer Prev. Res., 6(1): 59-69, 2013.
van Heesch, S., Mokry, M., Boskova, V., Junker, W., Mehon, R., Toonen, P., de Bruijn, E., Shull, J. D., Aitman, T. J., Cuppen, E., and Guryev, V. Systematic Biases in DNA Copy Number Originate from Isolation Procedures. Genome Biol., 14(4):R33, 2013.
Member, National Institutes of Health Cancer Genetics Study Section, 2009-present