Venezia by PVII

Jeffrey M. Rosen, M.D., Ph.D.

C.C. Bell Professor, Department of Molecular and Cellular Biology
Acting Director, Medical Scientist Training Program
Baylor College of Medicine

Ph.D., SUNY at Buffalo , Roswell Park Division
Postdoctoral Training: Vanderbilt University School of Medicine

Awards: Endocrine Society Edwin B. Astwood Lecture Award 2000.
Michael E. DeBakey, M.D., Excellence in Research Award 2004

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.

Rosen Lab:

Representative publications:

Salvetti P, Rosen JM, Reichel E. Subthreshold infrared footprinting with indocyanine green for localizing low-intensity infrared photocoagulation. Ophthalmic Surg Lasers Imaging. 34(1):44-48, 2005. Erratum in: Ophthalmic Surg Lasers Imaging. 34(2):135, 2005.

Xian W, Schwertfeger KL, Vargo-Gogola T, Rosen JM. Pleiotropic effects of FGFR1 on cell proliferation, survival, and migration in a 3D mammary epithelial cell model. J Cell Biol. 171(4):663-673, 2005.

Behbod F, Xian W, Shaw CA, Hilsenbeck SG, Tsimelzon A, Rosen JM. Transcriptional Profiling of Mammary Gland Side Population Cells. Stem Cells. Nov 10, 2005; [Epub ahead of print].

Grimm SL, Contreras A, Barcellos-Hoff MH, Rosen JM. Cell cycle defects contribute to a block in hormone-induced mammary gland proliferation in CCAAT/enhancer-binding protein (C/EBPbeta)-null mice. J Biol Chem. 280(43):36301-36309, 2005.

Woodward WA, Chen MS, Behbod F, Rosen JM. On mammary stem cells. J Cell Sci. 118(Pt 16):3585-3594, 2005.

Li Y, Rosen JM. Stem/progenitor cells in mouse mammary gland development and breast cancer. J Mammary Gland Biol Neoplasia. 10(1):17-24, 2005.

Chang WT, Rosen JM. Potential for epinephrine overdose in liposuction. Plast Reconstr Surg. 115(3):956, 2005.

Rosen JM. Hormone receptor patterning plays a critical role in normal lobuloalveolar development and breast cancer progression. Breast Dis. 18:3-9, 2003.

Lam MH, Rosen JM. Chk1 versus Cdc25: chking one's levels of cellular proliferation. Cell Cycle. 3(11):1355-1357, 2004.

Behbod F, Rosen JM. Will cancer stem cells provide new therapeutic targets? Carcinogenesis. 26(4):703-711, 2005.

Lam MH, Liu Q, Elledge SJ, Rosen JM. Chk1 is haploinsufficient for multiple functions critical to tumor suppression. Cancer Cell. 6(1):45-59, 2004.

Hernandez I, Maddison LA, Wei Y, DeMayo F, Petras T, Li B, Gingrich JR, Rosen JM, Greenberg NM. Prostate-specific expression of p53(R172L) differentially regulates p21, Bax, and mdm2 to inhibit prostate cancer progression and prolong survival. Mol Cancer Res. 1(14):1036-1047, 2003.

Freeman KW, Welm BE, Gangula RD, Rosen JM, Ittmann M, Greenberg NM, Spencer DM. Inducible prostate intraepithelial neoplasia with reversible hyperplasia in conditional FGFR1-expressing mice. Cancer Res. 63(23):8256-8263, 2003.

Li Y, Welm B, Podsypanina K, Huang S, Chamorro M, Zhang X, Rowlands T, Egeblad M, Cowin P, Werb Z, Tan LK, Rosen JM, Varmus HE. Evidence that transgenes encoding components of the Wnt signaling pathway preferentially induce mammary cancers from progenitor cells. Proc Natl Acad Sci U S A. 100(26):15853-15858, 2003. Grimm SL, Rosen JM. The role of C/EBPbeta in mammary gland development and breast cancer. J Mammary Gland Biol Neoplasia. 8(2):191-204, 2003.

Rosen JM. Transcription factors. J Mammary Gland Biol Neoplasia. 8(2):143-144, 2003.

Contreras A, Hale TK, Stenoien DL, Rosen JM, Mancini MA, Herrera RE. The dynamic mobility of histone H1 is regulated by cyclin/CDK phosphorylation. Mol Cell Biol. 23(23):8626-8636, 2003.

Freeman KW, Gangula RD, Welm BE, Ozen M, Foster BA, Rosen JM, Ittmann M, Greenberg NM, Spencer DM. Conditional activation of fibroblast growth factor receptor (FGFR) 1, but not FGFR2, in prostate cancer cells leads to increased osteopontin induction, extracellular signal-regulated kinase activation, and in vivo proliferation. Cancer Res. 63(19):6237-6243, 2003.

Welm B, Behbod F, Goodell MA, Rosen JM. Isolation and characterization of functional mammary gland stem cells. Cell Prolif. 36(Suppl 1):17-32, 2003.

Rijnkels M, Elnitski L, Miller W, Rosen JM. Multispecies comparative analysis of a mammalian-specific genomic domain encoding secretory proteins. Genomics. 82(4):417-432, 2003.

Rosen JM. Striking it rich by data mining. Cell. 114(3):271-272, 2003.

Ginger MR, Rosen JM. Pregnancy-induced changes in cell-fate in the mammary gland. Breast Cancer Res. 5(4):192-197, 2003.

Lee AV, Zhang P, Ivanova M, Bonnette S, Oesterreich S, Rosen JM, Grimm S, Hovey RC, Vonderhaar BK, Kahn CR, Torres D, George J, Mohsin S, Allred DC, Hadsell DL. Developmental and hormonal signals dramatically alter the localization and abundance of insulin receptor substrate proteins in the mammary gland. Endocrinology. 144(6):2683-2694, 2003.

Pownall ME, Welm BE, Freeman KW, Spencer DM, Rosen JM, Isaacs HV. An inducible system for the study of FGF signalling in early amphibian development. Dev Biol. 256(1):89-99, 2003.

Chakravarty G, Hadsell D, Buitrago W, Settleman J, Rosen JM. p190-B RhoGAP regulates mammary ductal morphogenesis. Mol Endocrinol. 17(6):1054-1065, 2003.

Kabotyanski EB, Rosen JM. Signal transduction pathways regulated by prolactin and Src result in different conformations of activated Stat5b. J Biol Chem. 278(19):17218-17227, 2003.

Medina D, Kittrell FS, Shepard A, Contreras A, Rosen JM, Lydon J. Hormone dependence in premalignant mammary progression. Cancer Res. 63(5):1067-1072, 2003.

Tepera SB, McCrea PD, Rosen JM. A beta-catenin survival signal is required for normal lobular development in the mammary gland. J Cell Sci. 116(Pt 6):1137-1149, 2003.


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