Jeffrey M. Rosen, Ph.D.
C.C. Bell Professor
Department of Molecular and Cellular Biology
Ph.D.: State University of New York, Buffalo
Postdoctoral training: Vanderbilt School of Medicine, Nashville
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.
The Perichromosomal Layer
- Atkinson RL, Zhang M, Diagaradjane P, Peddibhotla S, Contreras A, Hilsenbeck S, Woodward W, Krishnan S, Chang J and Rosen JM.(2010) Thermal enhancement with optically active gold nanoshells sensitizes breast cancer stem cells to radiation therapy, Sci. Transl. Med., 2, 55ra79. PMID: 20980696.
- Herschkowitz JI, Zhao W, Zhang M, Usary J, Murrow G, Edwards D, Knezevic J, Greene SB, Darr D, Troester MA, Hilsenbeck S, Medina D, Perou CM and Rosen JM. (2011) Comparative oncogenomics identifies breast tumors enriched in functional tumor initiating cells. Proc. Natl. Acad Sci, USA, June 1. [Epub ahead of print]. PMID: 21633010.
- Pond AC, Herschkowitz JI, Schwertfeger KL, Welm B, Zhang Y, York B, Murrow G, Cardiff RD, Hilsenbeck S, Perou CM, Creighton CJ, Lloyd RE and Rosen JM. (2010). FGFR signaling dramatically accelerates tumorigenesis and enhances oncoprotein translation in the mouse mammary tumor virus-Wnt1 mouse model of breast cancer, Cancer Res, 70:4868-79. PMID: 20501844
- Greene SB, Gunaratne PH, Hammond SM and Rosen JM. (2010). A putative role for microRNA205 in progenitors of mammary epithelial cells. J. Cell Sci, 123:606-618. PMID 20103531.
- Zhang M, Atkinson RL and Rosen JM. (2010). Selective targeting of radiation-resistant tumor-initiating cells. Proc. Natl. Acad. Sci. USA. 107: 3522-7. PMID 20133717.
- Rosen JM and Jordan CT. (2009). The increasing complexity of the cancer stem cell paradigm, Science, 324:1670-3. PMID: 19556499
- Peddibhotla S, Lam MH, Gonzalez-Rimbau M and Rosen JM. (2009). The DNA-damange effector checkpoint kinase 1 is essential for chromosome segregation and cytokinesis. Proc. Natl. Acad. Sci. USA, 106: 5159-5164. PMID: 19289837
- Creighton C, Li X, Landis M, Dixon JM, Neumeister VM, Sjolund A, Rimm DL, Wong H, Rodriguez A, Herschkowitz JI, Fan C, Zhang X, He X, Pavlick A, Gutierrez MC, Renshaw L, Larionov AA, Faratian D, Hilsenbeck SG, Perou CM, Lewis MT, Rosen JM and Chang JC. (2009). Residual breast cancers after conventional therapy display mesenchymal as well as tumor-initiating features, Proc. Natl. Acad. Sci,, USA, 106:13820-5. PMID: 19666588.
- Kabotyanski EB, Rijnkels M, Buser AC, Edwards DP and Rosen JM. (2009). Lactogenic hormonal induction of long distance interactions between ß-casein gene regulatory elements, J. Biol. Chem. 284:22815-24. PMID: 19542223.
- Zhang M, Behbod F, Kittrell F, Edwards D, Medina D, Tsimelzon A, Hilsenbeck SG, Green JE, Michalowska A and Rosen JM. (2008). Identification of tumor-initiating Cells in a p53 null mouse model of breast cancer, Cancer Research, 68:4674-4682. PMID: 18559513.