Sallie W. SmithAdjunct Research Assistant Professor
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Signaling During Mammary Gland Development and CarcinogenesisDevelopment of the mature mammary gland requires numerous signaling pathways engaged by secreted factors and cell:cell interactions. My overall interest is in studying the signaling pathways that control normal and abnormal development in the mammary gland, as well as the role of communication between various cellular compartments in these processes. In the past few years we have focused on the role of Notch receptor proteins during normal and abnormal development. The Notch family of proteins is comprised of four extracellular membrane-associated receptors (Notch 1-4) whose structure and function have been highly conserved throughout evolution. Signaling through these receptors is initiated by ligand on adjacent cells, which results in activation through proteolytic cleavage events at the membrane. The cytoplasmic domain is released and translocates to the nucleus where it participates in numerous protein:protein interactions which affect transcription. Transgenic studies have indicated that deregulated
expression of the Notch4 receptor results in a retarded growth of the
epithelial cell compartment of the mammary gland and a block in lobulo-alveolar
development. Furthermore, these mice develop breast tumors within three
to six months. My lab has been studying signaling pathways induced by
Notch receptors and how these pathways interact with a number of other
signaling pathways involved in mammary gland development. I am particularly
interested in the interplay between Notch signaling and steroid receptor
transactivation, p53 activation, and activation of epidermal growth
factor receptor family members. Activation of Notch receptors in one
cell also appears to initiate an interesting set of communicative events
with neighboring cells. Secretion of various factors and changes in
cell surface receptors appear to modulate the normal responses in other
cellular compartments and affect immune surveillance in co-culture assays.
These events may be as important as the internal signaling pathways
in the turn towards malignant growth. |
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Representative Recent Publications:Murphy L.O., Smith S., Chen R.H., Fingar D.C., and J.Blenis (2002) Regulation of the immediate early gene product c-Fos by ERK and RSK: a mechanism for sensing and propagating ERK signal duration. Nature Cell Biology 4(8):556-564. Sandhu K.K., Simard J.M., McIntosh C.M., Smith S.W., and V.M. Rotello. (2002) Gold nanoparticle-mediated transfection of mammalian cells. Bioconjugate Chemistry 13(1):3-6 Gordo C.A., He C.L., Smith S., and R.A. Fissore (2001) Mitogen Activated protein kinase plays a significant role in metaphase II arrest, spindle morphology, and maintenance of maturation promoting factor activity in bovine oocytes. Mol. Repro.and Dev.59:106-114 Morgan G., Smith S.W., Pak J., Marshak-Rothstein A., Fissore R., and B.A. Osborne (1999) Characterization of a mutant T cell hybridoma line with defects in TCR-mediated apoptotic pathway. Cell Death and Diff. 6:36-47. Smith S.W. and B.A. Osborne (1997) Private pathways to a common death. J. NIH Research 9:33-37. Smith S.W. and B.A. Osborne (1995) Molecular events in thymocyte apoptosis. In: Current Topics in Micro. & Immunol., Vol.200:147-162. Liu Z.G.*, Smith S.W.*, McLaughlin K.A., and L.M. Schwartz, Barbara A. Osborne (1994) "Apoptotic signals delivered through the T-cell receptor of a T-cell hybrid require the immediate-early gene nur77" Nature 367, 281-284. (*Contributed equally to this work) Lowe S.W., Schmitt E.M., Smith S.W., Osborne B.A., and T. Jacks (1993) "p53 is required for radiation-induced apoptosis in mouse thymocytes." Nature 362, 847-849. Schwartz L.M., Smith S.W., Jones M.E.E., and B.A. Osborne (1993) "Do all programmed cell deaths occur via apoptosis?" Proc. Natl. Acad. Sci. 90, 980-984. |
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