Jeffrey M. Rosen, Ph.D.
Charles C. Bell Professor in Cell Biology
Co-Director, M.D./Ph.D. - Medical Scientist Training Program
- B.A., Williams College, Williamstown, MA, 1966
- Ph.D., State University of New York, Buffalo, 1971
- Postdoc, Vanderbilt University School of Medicine, Nashville, TN, 1970-72
Mammary Gland Development and Breast Cancer
The research objectives of the Rosen laboratory are to elucidate the mechanisms regulating the normal development of the mammary gland including the hormonal control of milk protein gene expression, and to determine how these regulatory mechanisms have deviated in breast cancer. His laboratory is studying the role of systemic hormones, specifically prolactin, glucocorticoids, estrogens and progestins, and local growth factors, including members of the Wnt, Fgf and IGF families, on these processes. The role of specific transcription factors and their dominant-negative isoforms, including members of the C/EBP, Stat and NF I families, are also being examined using transgenic and knockout mouse models. Postnatal mammary gland development is being studied in knockout mice displaying late embryonic or neonatal mortality by transplantation of mammary epithelium into the cleared mammary gland fat pad of syngeneic recipients. Genetically engineered mice, coupled with FACS analysis and transplantation into the cleared mammary fat pad, have also been employed as model system in which to isolate and characterize functional mammary stem/progenitor cells. Transgenic and knockout mouse models are being used to elucidate changes in normal mammary gland stem cells and progenitors and signal transduction pathways that are involved in the progression from the normal mammary gland to preneoplasias, as well as the role of mutant p53 and Chk1 in genomic instability and the development of aneuploidy. These studies are being translated into the clinic to understand the mechanisms of therapeutic resistance of cancer stem cells to chemotherapy and radiation. Finally, studies are underway to elucidate the mechanisms by which noncoding RNAs regulate mammary gland development and are altered in breast cancer.
- Heckman, BM, Chakravarty G, Vargo-Gogola T, Gonzales-Rimbau M, Hadsell DL, Lee AV, Settleman J and Rosen JM. (2007). Crosstalk between the p190-B RhoGAP and IGF signaling pathways is required for embryonic mammary bud development. Dev. Biol. doi 10.1016/j.ydbio.2007.07.002
- Vargo-Gogola T and Rosen JM. (2007). Modeling breast cancer: One size does not fit all. Nature Rev. Cancer 7:1-14. doi:10.1038/nrc2193
- Woodward WA, Chen MS, Behbod F, Alfaro MP, Buchholz TA and Rosen JM. (2007). Wnt/ß-Catenin Mediates Radiation Resistance of Mouse Mammary Progenitor Cells, Proc. Natl. Acad. Sci. USA 104:618-623.
- Chen MS, Woodward WA, Behbod F, Peddibhotla S, Alfaro MP, Buchholz TA and Rosen JM. (2007). Wnt/ß-Catenin Mediates Radiation Resistance of Stem Cell Antigen-1 Positive Progenitors in an Immortalized Mammary Gland Cell Line, J. Cell Sci. 120:468-477.
- Vargo-Gogola T, Heckman BH, Chodosh LA and Rosen JM. (2006). P190-B Rho GTPase-activating protein overexpression disrupts ductal morphogenesis and induces hyperplastic lesions in the developing mammary gland. Mol. Endo. 20:1391-1405.
- Kabotyanski EB, Huetter M, Xian W, Rijnkels M and Rosen JM. (2006). Integration of prolactin and glucocorticoid signaling at the ß-casein promoter and enhancer by ordered recruitment of specific transcription factors and chromatin modifiers. Mol. Endo. 20:2055-2368.
- Schwertfeger K, Xian W, Burnett SH, Kaplan AM, Cohen DA and Rosen JM. (2006). A Critical Role for the Inflammatory Response in a Mouse Model of Breast Cancer Progression. Cancer Res. 66:5676-5685.
- Ginger MR, Shore AN, Contreras A, Rijnkels M, Miller J, Gonzalez-Rimbau MF and Rosen JM. (2006). A Noncoding RNA is a Potential Marker of Cell Fate During Mammary Gland Development. Proc. Natl. Acad. Sci. USA 103:5781-5786.
- Zhang M and Rosen JM. (2006). Stem/progenitor cells in etiology and treatment of cancer. Current Opinion in Genetics & Development 16: 1-5.
- Lam MH, Liu Q, Elledge SJ and Rosen JM. (2004). Chk1 is haploinsufficient for multiple functions critical to tumor suppression. Cancer Cell 6:45-59.