Professor, Baylor College of Medicine
Charles C. Bell Professor in Cell Biology
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
Developmental and hormonal regulation of mammary gland gene expression and breast cancer
The research objectives of my 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.
Critical periods of postnatal development in the mouse mammary gland include ductal proliferation and branching that occur during sexual maturity, lobuloalveolar proliferation that occurs during pregnancy, terminal differentiation that results in lactation, and involution characterized by increased apoptosis and extensive tissue remodeling. Studies of the role of systemic hormones (viz., prolactin, glucocorticoids, estrogens and progestins) and local growth factors, including members of the Wnt, Fgf, and IGF families, on each of these processes are under way. 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. Gene arrays and subtractive hybridization techniques are employed to identify downstream targets of these transcription factors. 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 has also been employed as model system in which to isolate and characterize functional mammary progenitors and stem cells. Finally, 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.
Heckman BM, Chakravarty G, Vargo-Gogola T, Gonzales-Rimbau M, Hadsell DL, Lee AV, Settleman J, Rosen JM (2007) Crosstalk between the p190-B RhoGAP and IGF signaling pathways is required for embryonic mammary bud development. Developmental Biology 309:137-149.
Xian W, Schwertfeger KL, Rosen JM (2007) Distinct roles of fibroblast growth factor receptor 1 and 2 in regulating cell survival and epithelial-mesenchymal transition. Molecular Endocrinology 21:987-1000.
Kabotyanski EB, Rijnkels M, Freeman-Zadrowski C, Buser AC, Edwards DP, Rosen JM (2009) Lactogenic hormonal induction of long distance interactions between beta-casein gene regulatory elements. Journal of Biological Chemistry 284:22815-22824.
Peddibhotla S, Lam MH, Gonzalez-Rimbau M, Rosen JM (2009) The DNA-damage effector checkpoint kinase 1 is essential for chromosome segregation and cytokinesis. Proceedings of the National Academy of Sciences USA 106:5159-5164.
Greene SB, Gunaratne PH, Hammond SM, Rosen JM (2010) A putative role for microRNA-205 in mammary epithelial cell progenitors. Journal of Cell Science 123:606-618.
LaMarca HL, Visbal AP, Creighton CJ, Liu H, Zhang Y, Behbod F, Rosen JM (2010) CCAAT/enhancer binding protein beta regulates stem cell activity and specifies luminal cell fate in the mammary gland. Stem Cells 28:535-544.
Pond AC, Herschkowitz JI, Schwertfeger KL, Welm B, Zhang Y, York B, Cardiff RD, Hilsenbeck S, Perou CM, Creighton CJ, Lloyd RE, Rosen JM (2010) Fibroblast growth factor receptor signaling dramatically accelerates tumorigenesis and enhances oncoprotein translation in the mouse mammary tumor virus-Wnt-1 mouse model of breast cancer. Cancer Research 70:4868-4879.
Zhang M, Atkinson RL, Rosen JM (2010) Selective targeting of radiation-resistant tumor-initiating cells. Proceedings of the National Academy of Sciences USA 107:3522-3527.
Herschkowitz JI, Zhao W, Zhang M, Usary J, Murrow G, Edwards D, Knezevic J, Greene SB, Darr D, Troester MA, Hilsenbeck SG, Medina D, Perou CM, Rosen JM (2012) Comparative oncogenomics identifies breast tumors enriched in functional tumor-initiating cells. Proceedings of the National Academy of Sciences USA 109:2778-2783.
Shore AN, Kabotyanski EB, Roarty K, Smith MA, Zhang Y, Creighton CJ, Dinger ME, Rosen JM (2012) Pregnancy-induced noncoding RNA (PINC) associates with polycomb repressive complex 2 and regulates mammary epithelial differentiation. PLoS Genetics 8:e1002840.
Pond AC, Bin X, Batts T, Roarty K, Hilsenbeck S, Rosen JM (2013) Fibroblast growth factor receptor signaling is essential for normal mammary gland development and stem cell function. Stem Cells 31:178-189.
Jeffrey M. Rosen, Ph.D.
Department of Molecular and Cellular Biology
Baylor College of Medicine
One Baylor Plaza M638
Houston, Texas 77030, U.S.A.
Tel: (713) 798-6210
Fax: (713) 798-8012