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.
Gregory KJ, Morin SM, Kubosiak A, Ser-Dolanski J, Schalet BJ, Jerry DJ, Schneider SS. The Use of Patient-Derived Breast Tissue Explants to Study Macrophage Polarization and the Effects of Environmental Chemical Exposure. Immunology & Cell Biology. July 29, 1-14 (2020)
Muse M, Titus AJ, Salas LA, Wilkins OM, Mullen C, Gregory KJ, Schneider SS, Crisi GM, Jawale RM, Otis CN, Christensen BC, Arcaro KF. Enrichment of CpG island shore region hypermethylation in epigenetic breast field cancerization. Epigenetics. April 7; 15 (10) 1093-1106 (2020)
Dunphy KA, Black A, Suresh S, Li Z, Ser-Dolansky J, Sharma A, Crisi GM, Makari-Judson G, Roberts AL, Bigelow C, Schneider SS, Arcaro KF, Browne EP Jerry DJ. Inter-individual variation in response to estrogen in human breast explants. Journal of Mammary Gland Biology and Neoplasia 25 (1)(2020)
Majhi PD, Sharma A, Roberts AL, Daniele E, Majewski AR, Chuong LM, Black AL, Vandenberg LN, Schneider SS, Dunphy KA, Jerry DJ (2020) Effects of benzophenone-3 and propylparaben on estrogen-receptor-dependent R-loops and DNA damage in breast epithelial cells and mice. Environmental Health Perspectives 128(1)
Gregory KJ, Roberts AL, Conlon EM, Mayfield JA, Hagen MJ, Crisi GM, Bentley BA, Kane JJ, Makari-Judson G, Mason HS, Yu J, Zhu LJ, Simin K, Johnson JPS, Khan A, Schneider BR, Schneider SS, Jerry DJ. (2019) Gene expression signature of atypical breast hyperplasia and regulation by SFRP1. Breast Cancer Research. June 27; 21(1):7
Krajewski D, Kaczenski E, Rovatti J, Polukort S, Thompson C, Dollard C, Schneider SS, Kinney S, Mathias CB Epigenetic regulation via altered histone acetylation results in suppression of mast cell function and mast cell-mediated food allergic responses. Frontiers in Immunology 9:2414 (2018)
Reeves KW, Schneider SS, Xue J, Kannan K, Mason H, Cash S, Johnson M, Makari-Judson G, Jerry DJ, Santana M ” Bisphenol-A in Breast Adipose Tissue of Breast Cancer Cases and Controls.” Environmental Research 167:735-738 (2018)
Williams KE, Jawale RM, Schneider SS, Otis CN, Pentecost BT and Arcaro KF “DNA Methylation in Breast Cancers: Differences based on Estrogen Receptor Status and Recurrence” Journal of Cellular Biochemistry (2018)
Zimmers SM, Browne EP, Williams KE, Jawale RM, Otis CN, Schneider SS, Arcaro KF “TROP2 Methylation and Expression in Tamoxifen-Resistant Breast Cancer” Cancer Cell International 18:94. (2018)
Wong K, Mora MC, Sultana N, Moriarty KP, Arenas RB, Yadava N, Schneider SS, Tirabassi MV “Evaluation of Rhodiola crenulata on Growth and Metabolism of NB-1691, a MYCN Amplified Neuroblastoma Cell Line” Tumor Biology 40(6) (2018)
Gregory KJ, Morin S Bentley B, Elsayad M, Crisi GM, and Schneider SS “The relationship between the calcium-sensing receptor and Secreted Frizzled Related Protein in the breast” Journal of Molecular Oncology Research 2(2): 27(2018)
Jerry DJ, Shull J, Hadsell DL, Rijnkels M, Dunphy KA, Schneider SS, Vandenberg LN, Majhi PD, Byrne C, Trentham-Dietz A “Genetic variation in sensitivity to estrogens and breast cancer risk.” Mammalian Genome29(1-2):24-37 (2018)
Gregory K, Morin S, Schneider SS “Regulation of early growth response 2 expression by secreted Frizzled Related Protein.” BMC Cancer 17(1):473 (2017)
Schneider SS, Henchey EM, Sultana N, Morin SM, Jerry DJ, Makari-Judson G, Crisi GM, Arenas RB, Johnson M, Mason HS, Yadava N “Individual-specific variation in the respiratory activities of HMECs and their bioenergetic response to IGF1 and TNFα.” Journal of Cellular Physiology 232(10):2750-2765 (2017)
Roubert A, Gregory K, Li Y, Pfalzer AC, Li J, Schneider SS, Wood RJ, Liu Z “The influence of tumor necrosis factor-α on the tumorigenic Wnt-signaling pathway in human mammary tissue from obese women” Oncotarget in press (2017)
Taslim C, Weng D, Brasky TM, Dumitrescu R, Huang K, Kallakury B, Krishnan S, Llanos A, Marian C, McElroy J, Schneider S, Spears S, Troester MA, Freudenheim J, Geyer S, and Shields P. “Discovery and Replication of microRNAs for Breast Cancer Risk using Genome-Wide Profiling” Oncotarget 7(52):86457-86468 (2016)
Wong K, Mora M , Skinner M, McRae-Page S, Crisi GM, Arenas RB, Schneider S, and Emrick T “Evaluation of polyMPC-Dox prodrugs in a human ovarian tumor model” Molecular Pharmaceutics 13(5):1679-87 (2016)
Bassa LM, Jacobs C, Gregory K, Henchey E, Ser-Dolansky J Schneider SS Rhodiola crenulata induces an early estrogenic response and reduces proliferation and tumorsphere formation over time in MCF7 breast cancer cell lines. Phytomedicine 23(1):87-94 (2016)
Dudek M, Wong K, Bassa LM, Mora M, Bassa L, Ser-Dolansky J, Henneberry J, Crisi GM, Arenas R, Schneider S “Antineoplastic Effects of R. crenulata on B16- F10 melanoma” Tumor Biology 36(12):9795-805 PMID 26159852 (2015)
Gregory K and Schneider S “Estrogen-mediated signaling is differentially affected by the expression levels of SFRP1 in mammary epithelial cells" Cell Biology International 39(7):873-9. (2015)
Mora MC, Bassa LM, Wong K, Tirabassi M, Arenas R, Schneider SS “Rhodiola crenulata Inhibits Wnt/ β-catenin Signaling in Glioblastoma” Journal of Surgical Research 197(2):247-255 (2015)
Yang HP, Schneider SS, Chisholm C, Browne EP, Mahmood S, Gierach GL, Lenington S, Anderton DL, Sherman ME, Arcaro KF “Association of TGF-β2 levels in breast milk with severity of breast biopsy diagnosis” Cancer Causes & Control 26(3):345-54 (2015)
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.