Changes in gene expression underlie many fundamental cellular processes, including growth, differentiation, and tumorigenesis. The research in our laboratory focuses on the CCAAT/enhancer binding protein (C/EBP) family of transcription factors, which belong to the basic-leucine zipper (bZIP) class of DNA-binding proteins. The C/EBP proteins (C/EBPa, C/EBPb, C/EBPd, C/EBPe, and C/EBPg) recognize a common DNA sequence, exhibit similar leucine zipper dimerization specificities and, with the exception of C/EBPg, function mainly as transcriptional activators. Our research is aimed at elucidating the roles of C/EBP proteins in regulating cell growth and differentiation, as well as cellular responses to stress and inflammation. We are also interested in understanding the mechanisms that control the activity of C/EBP proteins in response to specific signal transduction pathways. Other projects involve determining the dimeric status of C/EBP proteins in cells and investigating how changes in dimerization partners affect their transcriptional activity. We are using cell culture systems as well as mouse models (targeted mutations) to address these questions. Recently, we have begun to investigate the involvement of C/EBP proteins in oncogenic transformation and tumorigenesis. C/EBPs can cause cell growth arrest when expressed in dividing cells, but have also been reported to promote cell proliferation in response to specific growth signals. These observations suggest that C/EBP proteins might function as tumor suppressors and/or as pro-oncogenes, depending on the C/EBP family member and the cell type involved. Studies using mice carrying null mutations in specific C/EBP genes indicate that these proteins are involved as both positive and negative regulators of tumorigenesis.
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