One in eight women will be diagnosed with breast cancer in her lifetime. This risk is altered by several genetic, environmental, and lifestyle factors. For example, a full-term pregnancy by the age of 20 will significantly reduce a woman's risk of developing breast cancer. However, a family history of the disease, early menarche, late menopause, and high Body Mass Index (BMI) in the postmenopausal years correlate with an increased risk.
We are interested in signaling pathways that alter the balance between protection against breast cancer and increased risk of the disease. Through this work, we hope to identify targets for preventive therapy. We have created a catalog of normal human breast tissue samples from women with different reproductive histories, ages, and weights and examined these samples to isolate important changes that occur in the higher-risk individuals. We are particularly interested in molecules that regulate sensitivity to apoptosis, DNA repair, and how the cells deal with stress. One specific target is an antagonist of the Wnt pathway called secreted frizzled-related protein. We have been studying the effects of differential expression of this protein on a number of critical signaling pathways and on normal and malignant development in the breast. Signals from immune cells, fibroblasts, and adipocytes all appear to contribute to differentiation and breast cancer development. Developing a better understanding of the interactions between these cell types and their link to normal and abnormal breast tissue is one of our primary goals.
Finally, we are interested in novel or complementary therapeutic strategies for breast cancer. We work with several polymer scientists to improve drug-delivery mechanisms for the treatment of breast cancer. We also are working to determine whether a plant extract employed in Eastern medicine can be used to decrease the risk of metastasis and to protect the normal cells of the body from the toxic effects of radiation and chemotherapy.
Page SM, Henchey E, Chen X, Schneider SS and Emrick T (2014) ‘Efficacy of polyMPC-DOX prodrugs in 4T1 tumor-bearing mice’ Molecular Pharmaceutics 11(5):1715-2
Sturgeon SR, Arcaro KF, Johnson MA, Balsubramanian R, Zorn M, JerryDJ and Schneider SS (2014)‘DNA methylation in paired breast epithelial cells and white blood cells from women undergoing reduction mammoplasty’ Anticancer Research 34(6):2985-90
Gauger KJ, Bassa LM, Henchey EM, Wyman J, Ser-Dolansky J, Shimono A, and Schneider SS (2014)“The effects of diet induced obesity on breast cancer associated pathways in mice deficient SFRP1” Molecular Cancer 13:117
Rotunno M, Sun X, Figueroa J, Sherman M, Garcia-Closas M, Meltzer P, Williams T, Schneider SS, Jerry DJ, Yang XR, Troester MA (2014) ‘Parity-related molecular signatures and breast cancer subtypes by estrogen receptor status’ Breast Cancer Research 16(4)
Gauger KJ, Bassa LM, Henchey EM, Wyman J, Bentley B, Brown M, Shimono A, and Schneider SS (2013) “Mice Deficient in SFRP1 exhibit increased adiposity, deregulated glucose metabolism, and enhanced macrophage infiltration” PLOS One 8(12)
Gauger KJ and Schneider SS (2013) “Tumor suppressor Secreted Frizzled Related Protein 1 regulates p53-mediated apoptosis” Cell Biology International 38(1):124-30
Pirone JR, D’Arcy M, Stewart DA, Gould MN, Yaswen P, Jerry DJ, Schneider SS, Troester MA (2012) “Age-associated gene expression in normal breast tissue mirrors qualitative age-at-incidence patterns for breast cancer” Cancer Epidemiology Biomarker& Prevention 21(10):1735-44.
Chen X, Parelkar S, Henchey E, Schneider SS, Emrick T, (2012) “PolyMPC-Doxorubicin Prodrugs” Bioconjugate Chemistry 23(9):1753-63
Gauger K, Shimono A, Crisi G, and Schneider SS (2012) “Loss of SFRP1 promotes Ductal branching in the murine mammary gland” BMC Developmental Biology 12:25
McRae S, Chen X, Kratz K, Samanta D, Henchey E, Schneider SS and Emrick T (2012) “Pentafluorophenyl Ester Functionalized Phosphorylcholine Polymers: Preparation of Linear, Two-arm and Grafted Polymer-Protein Conjugates” Biomacromolecules 13(7):2099-109
Sun X, Casbas, Hernandez P, Makowski L, Bigelow C, Jerry DJ, Schneider SS, Troester MA (2012). “Normal breast tissue of obese women is enriched for macrophage markers and macrophage-associated gene expression”. Breast Cancer Res Treat. 131(3):1003-12
Gauger KJ, Chenausky KL, Murray ME, Schneider SS. SFRP1 reduction results in an increased sensitivity to TGF-β signaling. BMC Cancer. 2011;11:59.
Compton S, Kim C, Griner N, Potluri P, Scheffler IE, Sen S, Jerry DJ, Schneider SS, Yadava N. Mitochondrial dysfunction impairs tumor suppressor P53- expression/function. J Biol Chem. In press (2011).
Wong CM, Anderton DL, Schneider SS, Wing MA, Greven MC, Arcaro KF. Quantitative analysis of promoter methylation in exfoliated epithelial cells isolated from breast milk of healthy women. Epigenetics. 2010;5(7):645-655.
Gauger K, Schneider SS. Rhodiola and related plants: a role in cancer prevention and therapy. In: Watson RR, Preedy VR, eds. Bioactive Foods and Extracts: Cancer prevention and Treatment. Boca Raton, FL: Taylor and Francis Group; 2011:37-48.
Gauger K, Rodriguez-Cortes A, Hartwich M, Schneider SS. Rhodiola crenulata inhibits the tumorigenic properties of invasive mammary epithelial cells with stem cell characteristics. J Med Plant Res. 2010;4(6):446-454.
Troester M, Lee MH, Carter M, Fan C, Pirone J, Perou C, Jerry DJ, Schneider SS. Activation of host wound response in breast cancer microenvironment. Clin Cancer Res. 2009;15(22):7020-7028.
Gauger K, Hugh J, Troester M, Schneider SS. Down-regulation of SFRP1 in a mammary epithelial cell line promotes the development of a cd44high/cd24low population which is invasive and resistant to anoikis. Cancer Cell Int. 2009;9(1):11.
Mathews L, Schneider SS. Insulin-like growth factor inhibits estrogen and progesterone mediated growth regulatory responses in the mammary gland. Eur J Cancer Prev. 2008;17(4):297-305.
Tu Y, Shetty K, Schneider SS. Rhodiola crenulata induces cell death and inhibits growth of breast cancer cell lines. J Med Food. 2008;11(3):413-423.
Tu Y, Pazik B, Jerry DJ, Schneider SS. Sensitivity to DNA damage is a common component of hormone based strategies for protection of the mammary gland. Mol Cancer Res. 2005;3(8):435-442.
Murphy LO, Smith SW, Chen R-H, Fingar DG, Blenis J. Molecular interpretation of ERK signal duration by immediate early gene products. Nat Cell Biol. 2002;4(8):556-564.
Smith SW, Osborne BA. Molecular events in thymocyte apoptosis. Curr Top Microbiol Immunol. 1995;200:147-162.
Osborne BA, Smith SW, Liu Z-G, McLaughlin K, Grimm L, Schwartz LM. Identification of genes induced during apoptosis in T lymphocytes. Immunol Rev. 1994;141:301-320.
Liu Z-G, Smith SW, McLaughlin KA, Schwartz LM, Osborne BA. Apoptotic signals delivered through the T-cell receptor of a T-cell hybrid require the immediate-early gene nur77. Nature. 1994;367(6460):281-184.
Lowe SW, Schmitt EM, Smith SW, Osborne BA, Jacks T. P53 is required for radiation-induced apoptosis in mouse thymocytes. Nature. 1993;362:847-849.
Schwartz LM, Smith SW, Jones MEE, Osborne BA. Do all programmed cell deaths occur via apoptosis? Proc Natl Acad Sci. 1993;90:980-984.