Rebecca Fillmore, Ph.D.
Assistant Professor of Biological Sciences
Gulf Park Campus
Science Building 309B
Ph.D., Cellular and Structural Biology, University of South Alabama, Mobile, AL
B.S., Cellular and Molecular Biology Pre-professional, University of West Florida, Pensacola, FL
BSC 360 Cell Biology
My general research interest is in the role(s) of mammalian gene regulatory and coactivator proteins and their respective transcriptional regulatory complexes in diseased processes, particularly cancer. My research focuses on the involvement of a superfamily of genes called homeodomain proteins and their related coactivator proteins in cancer (particularly in breast). Cells require accurate spatial and temporal regulation of gene expression throughout development to acquire their proper functional state. Thus, misexpression of those genes could lead to altered characteristics (such as loss of cell cycle or apoptotic control and/or altered cell-cell adhesions, cell shape, cell motility, and hormone/growth factor responses) which could easily contribute to a cancerous state. Such developmental decisions in many cells are determined by homeodomain factors, which are sequence-specific transcription factors. Often times sequence-specific transcription factors (including the homeodomain factors) utilize accessory factors (coactivator proteins), which serve to function as bridging factors connecting sequence-specific transcription factors to the basal transcription machinery, to exert their specific effects.
Evidence has accumulated that altered homeodomain and specific coactivator gene function play a causal role in development of some cancers (leukemia, prostate cancer). In addition, there is also circumstantial evidence, albeit somewhat limited, for their involvement in breast cancer. For example, studies have demonstrated differences in expression of one of two of the major groups of homeodomain proteins, called Hox factors, in normal versus cancerous tissues and cell lines. A few studies also implicate the other class of homeodomains, the NK factors, in breast development and cancer. For example, NK 2.5 affects radioiodide uptake in the breast, thus becoming a target for breast cancer therapy. Studies with the coactivator FHL2 have shown its upregulation in aggressive breast cancer versus normal cells which corresponded to deleterious effects on gene expression.
Since preliminary studies implicate the importance of homeodomain factors and coactivators in breast cancer initiation and/or progression, the focus of my research will be to validate and determine the role(s) of homeodomain proteins and related coactivators in various aspects of breast cancer biology. Studies in my laboratory will rely heavily on molecular biological as well as cell biology-based techniques (quantitative real-time RT-PCR, Western blot analyses, transfections, siRNA technologies, microarray, immunofluoresence microscopy, FACS analyses) and collaborative efforts with colleagues at the University of Southern Mississippi, the Mitchell Cancer Institute in Mobile, AL, and Texas A & M University in Houston, TX. Overall, these studies are paramount as they will help fill the void in the scientific literature concerning homeodomain and coactivator gene involvement in cancer progression, yield an improved understanding of the mechanisms of tumorigenesis, and may lead to the development of novel, therapeutic strategies to combat breast cancer.
Feng, X., Wang, Z., Fillmore, R.A., Xi, Y. 2013. MiR-200, a new star miRNA in human cancer. Cancer Lett. pii: S0304-3835(13)00806-9.
Fillmore, R.A., Mitra, A., Shevde, L.A., and Samant, R.S. 2009. Nmi (N-Myc interactor) inhibits Wnt/beta-catenin signaling and retards tumor growth. Int. J. Cancer. 125(3):556-564.
Clark, D.W., Mitra, A., Fillmore, R.A., Jiang, W.G., Samant, R.S., Fodstad, O., Shevde, L.A. 2008. Nupr1 interacts with p53, transcriptionally regulates p21 and rescues breast epithelial cells from doxorubicin-induced genotoxic stress. Current Cancer Drug Targets 8(5):421-430.
Zhang, Y., Fillmore, R.A., and Zimmer, W.E. 2008. Structural and functional analysis of domains mediating interaction between the bagpipe homologue, Nkx3.1 and serum response factor. Exp. Biol. and Med. 233(3):297-309.
Mitra, A., Fillmore, R.A., Metge, B.J., Mathur, R., Xi, Y., King, J., Ju, J., Pannell, L., Shevde, L.A., Samant, R.S. 2008. Large isoform of MRJ (DNAJB6) reduces malignant activity of breast cancer cell lines. Breast Cancer Research 10:R22 (doi:10.1186/bcr1874).
Samant, R.S., Clark, D., Fillmore, R.A., Metge, B.J., Chandramouli, K.H., Chambers, A.F., Casey, G., Welch, D.R., and Shevde, L.A. 2006. Breast cancer metastasis suppressor 1 (BRMS1) inhibits osteopontin transcription by abrogating NF-Kappa B activation. Mol. Cancer. 6:6 (doi:10.1186/1476-4598-6-6).
Ritchie, M.H., Fillmore, R.A., Lausch, R.N., and Oakes, J.E. 2004. A role for NF-kappaB binding motifs in the differential induction of chemokine gene expression in human corneal epithelial cells. Invest. Ophthalm. Vis. Sci. 45:2299-2305.
Fillmore, R.A., Nelson, S.E., Lausch, R.N., and Oakes, J.E. 2003. Differential regulation of ENA-78 and GCP-2 gene expression in human corneal keratocytes and epithelial cells. Invest. Ophthalm. Vis. Sci. 44:3432-3437.
Carson, J.A., Culberson, D., Thompson, R., Fillmore, R., and Zimmer, W. 2003. Smooth muscle gamma-actin promoter regulation by RhoA and serum response factor signaling. Biochem. Biophys. Acta. 1628:133-139.
Fillmore, R.A., and Zimmer, W.E. 2002. The smooth muscle gamma actin gene is androgen-responsive in prostate epithelia. Gene Expression, 10:201-211.
Fillmore, R.A., and Zimmer, W.E. 2000. Identification of mRNA encoding homeobox proteins Hox b4 and Hox b5 in developing chicken gizzard tissues. Cell. & Mol. Biol. Lett. 5:495-509.
Carson, J.A., Fillmore, R.A., Schwartz, R.J., and Zimmer, W.E. 2000. The smooth muscle gamma-actin gene promoter is a molecular target for the mouse bagpipe homologue, mNkx3-1, and serum response factor. J. Biol. Chem. 275:39061-39072.
Browning, C.L., Culberson, D.E., Aragon, I.V., Fillmore, R.A., Croissant, J.D., Schwartz, R.J., and Zimmer, W.E. 1998. The developmentally regulated expression of serum response factor plays a key role in the control of smooth muscle-specific genes. Developmental Biology 194:18-37.