Susan L. Ruppert, PhDRank: Associate Professor
Division: Hematology & Oncology
Campus Address: WTI 558
Phone: (205) 934-9581
Susan Lobo-Ruppert obtained her Ph.D. in 1987 from Florida State University (mentor Dr. William F. Marzluff) and did postdoctoral work with Dr. Nouria Hernandez at Cold Spring Harbor Laboratory, NY. She joined UAB in 1993.
Role of transcription factor oncogenes in tumor initiation
We are using a variety of molecular biological, biochemical and genetic techniques to understand how the zinc finger transcription factors Gli1 and KLF4 initiate cancer. Gli1 is an effector of the hedgehog signaling pathway that has been implicated in basal cell, pancreatic and small cell lung cancers. We identified KLF4 as a transfroming oncogene present in a head and neck cancer cDNA library, by expression cloning in an epithelial cell line, RK3E. Monoclonal and polyclonal antibodies were raised against human KLF4 and used for immunohistochemistry. We discovered that KLF4 expression is upregulated in virtually all oral squamous cell carcinomas, in 75% of breast cancers and in a significant number of squamous cell carcinomas of the skin. In breast cancers, preferential nuclear localization of KLF4 is predictive of poor outcome. Our current studies are aimed at dissecting the mechanisms by which KLF4 and Gli1 function as oncogenes.
•Marzluff, W.F., Brown, D.T., Lobo, S.M. and Wang, S-S. (1983). Isolation and characterization of two linked mouse U1b small nuclear RNA genes. Nucl. Acids Res. 11, 6255-6270.
•Moussa, N.M., Lobo, S.M. and Marzluff, W.F. (1985). Expression of a mouse U1b gene in mouse L cells. Gene 36, 311-319.
•Blatt C, Saxe D, Marzluff WF, Lobo S. M., Nesbitt MN, Simon MI. (1988) Mapping and gene order of U1 small nuclear RNA, endogenous viral env sequence, amylase, and alcohol dehydrogenase-3 on mouse chromosome 3. Somat Cell Mol Genet. 14(2):133-42.
•Moussa, N.M., E-L Din, A.S., Lobo, S.M. and Marzluff, W.F. (1987). A mouse U1B gene with extensive sequence similarity to a rat U1A gene for 670 nucleotides 5′ to the gene. Nucl. Acids Res. 15, 3622. PDF
•Lobo, S.M. and Marzluff, W.F. (1987) Synthesis of snRNAs in isolated mouse cell nuclei: Initiation and 3′ end formation. Mol. Cell. Biol. 7, 4290-4296. PDF
•Lobo, S.M., Marzluff, W.F., Seufert, A.C., Dean, W.L., Schultz, G.A., Simerly, C., and Schatten, G. (1988). Localization and expression of U1 RNA in early mouse embryo development. Develop. Biol. 127 394-361.
•Lobo, S.M., and Hernandez, N. (1989) A 7 bp mutation converts a human RNA polymerase II snRNA promoter into an RNA polymerase III promoter. Cell 58, 55-67.
•Prather R, Simerly C, Schatten G, Pilch DR, Lobo S.M., Marzluff WF, Dean WL, Schultz GA. (1990) U3 snRNPs and nucleolar development during oocyte maturation, fertilization and early embryogenesis in the mouse: U3 snRNA and snRNPs are not regulated coordinate with other snRNAs and snRNPs. Dev Biol. 138(2):247-55
•Lobo, S.M., Ifill, S., and Hernandez, N. (1990) Cis-acting elements required for RNA polymerase II and III transcription in the human U2 and U6 snRNA promoters. Nucl. Acids Res. 18 2891-2899.
•Lobo, S.M., Lister, J., Sullivan, M.L., and Hernandez, N. (1991) The cloned RNA polymerase II transcription factor IID selects RNA polymerase III to transcribe the human U6 gene in vitro. Genes and Dev.. 5 1477-1489.
•Lobo, S.M., Tanaka, M., Sullivan, M.L., and Hernandez, N. (1992) A TBP complex essential for transcription from TATA-less but not TATA-containing RNA polymerase III promoters is part of the TFIIIB fraction. Cell 71 1029-1040.
•Abraham, S.E., Lobo, S.M., Yaciuk, P., Wang, H-G.H., and Moran, E. (1993) p300, and p300 associated proteins, are components of TATA binding protein (TBP) complexes. Oncogene, 8 1639-1647.
•Sadowski, C.L., Henry, W.W., Lobo, S.M., and Hernandez, N. (1993) Targeting TBP to a non-TATA box cis-regulatory element: A TBP containing complex activates transcription from snRNA promoters through the PSE. Genes and Dev.. 7: 1535-1548.
•Lobo, S.M. and Hernandez (1994) Transcription of snRNA promoters by RNA polymerases II and III. (Review) in Transcription: Mechanisms and Regulation. Edited by R.C. Conaway and J.W. Conaway. Raven Press, Ltd., New York. 127-159.
•Lobo Ruppert, S.M., McCulloch, V., Meyer, M. Bautista, C., Falkowski, M., Stunnenberg, H. G., Hernandez, N. (1995) Monoclonal antibodies directed against the amino-terminal domain of human TBP cross react with TBP from other species. Hybridoma. 15(1):55-68.
•Zhou, D., Frendewey, D., Lobo-Ruppert, S.M. (1999) Pac1p, an RNase III homolog, is required for formation of the 3' end of U2 snRNA in Schizosaccharomyces pombe. RNA, 5:1083-1098.
•McCulloch, V., Hardin, P., Peng, W., Ruppert, J.M., and Lobo-Ruppert, S.M. (2000) Alternatively spliced hBRF variants function at different RNA polymerase III promoters. EMBO J 19:4134-4143
•Zhou, D., and Lobo-Ruppert, S.M. (2001) Transcription of the Schizosaccharomyces pombe U2 gene in vivo and in vitro is directed by two essential promoter elements. Nuc. Acids Res. 29:2003-2011
•Pandya, A., Talley, L. I., Frost, A. R., Fitzgerald, T. J., Trivedi, V., Chakravarthy, M., Chhieng, D. C., Grizzle, W. E., Engler, J. A., Krontiras, H., Bland, K. I., LoBuglio, A. F., Lobo-Ruppert S. M, and Ruppert, J. M. (2004) Nuclear localization of KLF4 is associated with an aggressive phenotype in early stage breast cancer. Clin. Cancer Res. 10(8):2709-19.
•Foster, K. W., Liu, Z., Nail, C. D., Li, X., Fitzgerald, T. J., Bailey., S. K., Frost, A. R., Louro, I. D., Townes, T. M., Paterson, A. J., Kudlow, J. E., Lobo-Ruppert S. M, and Ruppert, J. M. Induction of KLF4 in basal keratinocytes blocks the proliferation-differentiation switch and initiates squamous epithelial dysplasia. Oncogene. 2005 Feb 24;24(9):1491-500.