Ruth A. Keri, PhD
Case Western Reserve Universitykeri@case.edu
Professor and Vice Chair
Case CCC Program Affiliation
Breast Cancer Program
Case CCC Associations
Associate Director for Basic Research
My laboratory studies the molecular mechanisms through which reproductive hormones and a member of the epidermal growth factor receptor family (Her-2/neu) regulate mammary gland development and breast cancer. Both processes are exquisitely regulated by hormonal input, thus it is likely that many of the events involved in mammary neoplasia are similar to those that occur during normal gland development. Using transgenic mouse models that involve overexpression of an oncogene specifically in the mammary gland, or disruption of the normal hormonal milieu, we are developing in vivo systems to assess the molecular mediators of proliferative or differentiation signals. Furthermore, we have coupled transgenic technology with gene expression microarrays to construct hierarchical pathways of development and oncogenesis. Hypotheses generated from these functional genomics approaches are continually tested using both in vitro cell culture models as well as newly derived transgenic mice. The ultimate goal of this work is to develop a molecular genetic road map of hormone-induced neoplasia with the purpose of identifying novel therapeutic targets for chemotherapy and chemoprevention of breast cancer.
Peiris, P.M., Tam, M., Vicente, P., Abramowski, A., Toy, R., Bauer, L., Mayer, A., Pansky, J., Doolittle, E., Tucci, S., Schmidt, E., Shoup, C., Rao, S., Murray, K., Gopalakrishnan, R., Keri, R.A., Basilion, J.P., Griswold, M.A., and Karathanasis, E. 2014. On-command drug release from nanochains inhibits growth of breast tumors. Pharm. Res.,31:1460-1468.
Shukla, S., Wen, A.M., Ayat, N.R., Commandeur, U., Gopalkrishnan, R., Broome, A,.-M., Lozada, K.W., Keri, R.A., and Steinmetz, N.F. 2014. Biodistribution and clearance of a filamentous plant virus in healthy and tumor-bearing mice.Nanomedicine, 9:221-235.
Sizemore, S.T., Sizemore, G.M., Booth, C.N., Thompson, C.L., Silverman, P., Bebek, G., Abdul-Karim, F.W., Avril, S., andKeri, R.A. 2014. Hypomethylation of the MMP7 promoter and increased expression of MMP7 distinguishes the basal-like breast cancer subtype from other triple-negative tumors. 2014. Breast Cancer Res. Treat., 146:25-40.
Yori, J.L., Lozada, K.L., Seachrist, D.D., Booth, C., Abdul-Karim, F.W., Flask, C., and Keri, R.A. 2014. Combined SFK/mTOR inhibition prevents rapamycin-induced feedback activation of AKT and elicits efficient tumor regression. Cancer Research,74:4762-4771.
Sizemore, G.M., Sizemore, S.T., and Keri, R.A. 2014. GABRP regulates ERK1/2 activity, cytokeratin expression and migration in basal-like breast cancer cells. J. Biol. Chem., 289:24102-24113.
Han, X., Zhang, L., Chung, J., Pozo, F.M., Seachrist, D. Jacobberger, J., Keri, R., Gilmore, H., and Zhang, Y. 2014. UBCH7 regulates 53BP1 stability and DSB repair. Proc. Natl. Acad. Sci., 111:17456-17461.
Bernardo, G.M., Bebek, G., Ginther, C.L., Sizemore, S.T., Lozada, K.L., Miedler, J.D., Anderson, L.A., Godwin, A.K., Abdul-Karim, F.W., Slamon, D.J., and Keri, R.A. 2013. FOXA1 actively represses the molecular phenotype of basal breast cancer cells.Oncogene, 32:554-563.
Asrani, K., Keri, R.A., Galidsteo, R., Brown, S., Horvat, S., Ghosh, A., Tran, N., Winkles, J. 2013. The HER2- and heregulin Î²1 (HRG)-inducible TNFR superfamily member Fn14 promotes HER-driven cell migration, invasion and MMP9 expression. Mol. Cancer Res.,11:393-404.