Smith Schneider Laboratory

Sallie Smith Schneider, Ph.D.

Telephone: 413.794.0941
Fax: 413.794.0587
Email
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Scientist, Associate Director of the Center of Excellence in Apoptosis Research
Adjunct Research Assistant Professor, Veterinary & Animal Sciences, University of Massachusetts Amherst

Education

B.A., Biology, Skidmore College
Ph.D. Immunology, University of Massachusetts Amherst

Postdoctoral Experience

Signaling, Harvard Medical School, 1995-1998
Cooperative phosphorylation of c-Fos by the ERK pathway and its role in proliferation

Pathways to breast cancer prevention

One in eight women will be diagnosed with breast cancer in their lifetime. The risk of this occurring is altered by several genetic and environmental and life style factors. For example, a full term pregnancy by the age of 20 will reduce one's risk of breast cancer by 50%. However, a family history of breast cancer, early menarche, exposure to DNA damaging agents or environmental toxicants during the ages of 12-15 or high levels of Insulin-like Growth Factor (IGF) correlate with an increased risk for breast cancer.

We are interested in signaling pathways which alter the balance of protection and increased risk in hopes of identifying important targets for preventive therapy. We are particularly interested in changes in retinoic acid signaling and how it relates to a release of p53 from its inactive state. We are also investigating how high levels of IGF may impede changes induced by pregnancy levels of hormones to impart protection. The pathways of interest all seem to relate back to the ability of the epithelium in the gland to respond to mutation through DNA repair or death. To this end a more in depth study analyzing pathways to apoptosis are underway in the lab. Signals from immune cells, fibroblasts, and adipocytes all appear to contribute to differentiation and breast cancer progression. We are trying to tease apart these signals and are investigating the regulation of the Notch and WNT pathways through these interactions.

Finally, we are interested in how nutritional elements may be responsible for imparting protection. This has been suggested from epidemiological data looking at the low rate of breast cancer in the Asian population. Interestingly, the protection is lost when these women migrate to Western countries suggesting that some dietary element(s) may be responsible for the change in susceptibility to breast cancer. We are currently looking at certain adaptogens (plant extracts with activities which allow for an easy adjustment to stressful situations) for their ability to act as chemopreventive or chemotherapeutic agents.

Working Groups:
Breast Cancer Working Group
Center of Excellence in Apoptosis Research (associate director)

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Publications:

Mathews L & Smith Schneider S Insulin like growth factor inhibits estrogen and progesterone mediated growth regulatory responses in the mammary gland. submitted

Kwon Y-I, Apostilidis E, Tu Y, Nichols A, Smith Schneider S, Shetty L Rhodiola crenulata-induced cell death in V14a breast cancer cell line involves dysfunctional mitochondrial oxidative phosphorylation associated with proline-linked pentose phosphate pathway. submitted

Y Tu, B Pazik, DJ Jerry, S Smith Schneider (2005) Sensitivity to DNA damage is a common component of hormone based strategies for protection of the mammary gland" Mol Cancer Res 3(8):435-442

J Zhang, Y Tu, S Smith Schneider (2005) “Activation of p53, inhibition of telomerase activity and induction of estrogen receptor beta are associated with the anti-growth effects of combination of ovarian hormones and retinoids in immortalized human mammary epithelial cells” Cancer Cell International 5:6

S Smith Schneider, LA Roberts, K Shetty (2005) "Phytochemicals and Breast Cancer Prevention" chapter in Food Biotechnology 2nd edition, McMillan Press

Klaus A Becker, Ellen S Dickinson, Sallie S. Schneider, D Joseph Jerry (2005) Estrogen and Progesterone regulate p53 activity in the mouse mammary epithelium through transforming growth factor beta dependent pathways. Oncogene.

Leon O. Murphy, Sallie Smith, Rey-Huei Chen, Diane C. Fingar, and John 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.

Grant Morgan, Sallie W. Smith, John Pak, Ann Marshak-Rothstein, Rafael Fissore, Barbara 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.

Sallie W. Smith and Barbara A.Osborne (1997) Private pathways to a common death. J. NIH Research 9:33-37.

Kelly McLaughlin, Sallie W. Smith, Carol E. Milligan, Wolfgang Bielke, Lawrence M. Schwartz, and Barbara A. Osborne (1997) The isolation and characterization of cell death genes. In: Weir's Handbook of Experimental Immunology, Blackwell Scientific.

Barbara A. Osborne, Sallie W. Smith, Kelly McLaughlin, Lisa Grimm, Grant M. Morgan, and Richard A. Goldsby (1996) Genetic regulation of apoptosis in the thymus. In: Advances in Experimental Medicine and Biology. 406:199-208.

Barbara A. Osborne, Sallie W. Smith, Kelly McLaughlin, Lisa Grimm, Tilman Kallinich, Zheng-Gang Liu and Lawrence M. Schwartz (1996) Genes that regulate apoptosis in the mouse thymus. J. Cell. Biochem. 60:18-22.

Barbara A. Osborne, Sallie W. Smith, Zheng-Gang Liu, Kelly McLaughlin, and Lawrence M. Schwartz (1995) Transient transfection assays to examine the requirement of putative cell death genes. In: Methods in Cell Biology: Cell Death. Vol.46:99-106, Academic Press, San Diego, CA.

Sallie W. Smith and Barbara A. Osborne (1995) Molecular events in thymocyte apoptosis. In: Current Topics in Micro. & Immunol., Vol.200:147-162.

Barbara A. Osborne, Sallie W. Smith, Zheng-Gang Liu, Kelly McLaughlin, Lisa Grimm, and Lawrence M. Schwartz (1994) Identification of genes induced during apoptosis in T lymphocytes. Immunological Reviews, Vol. 141:301-320.

Zheng-Gang Liu*, Sallie W. Smith*, Kelly A. McLaughlin, Lawrence 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)

Scott W. Lowe, Earlene M. Schmitt, Sallie W. Smith, Barbara A. Osborne, Tyler Jacks (1993) “p53 is required for radiation-induced apoptosis in mouse thymocytes.” Nature 362, 847-849.

Lawrence M. Schwartz, Sallie W. Smith, Margaret E.E. Jones, Barbara A. Osborne (1993) “Do all programmed cell deaths occur via apoptosis?” Proc. Natl. Acad. Sci. 90, 980-984.

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