Karen S. Katula
301 Eberhart Building
Gene regulation and cell cycle control.
Ph.D., Northwestern University
Research in my laboratory is focused on the general areas of cell growth control and gene regulation. We have studied the transcriptional regulation of human cyclin B1 gene expression during the S/G2 phase of the cell cycle and investigated the effects of nutrients on gene expression. Currently, we have a funded project to investigate changes in gene expression and cell signaling that result from reduced levels of cellular folate. The goal of this project is to provide a mechanistic understanding of the link between folate deficiency and various human conditions including cancer and developmental defects. Folates are an essential B vitamin that must be obtained from the diet. Folates facilitate the transfer of one-carbon units from donor molecules on to various substrates. Folates are critical in the synthesis of nucleotides required for DNA synthesis and homocysteine for production of S-adenosylmethionine, the major methyl donor in the cell. Reduced cellular folate levels have been associated with changes in protein and DNA methylation, increased DNA strand breaks, and more recently changes in expression of a wide variety of cellular genes.
We have compared gene expression in normal human cells grown in folate sufficient conditions to cells grown in folate depleted conditions by microarray analysis. From this study, we identified a group of genes whose mRNA transcripts were decreased or increased in folate deficient cells. The largest represented gene groups function in cell signaling, the cytoskeleton, and the extracellular matrix. Included were the genes DKK1, WISP1, and WNT5a, which function in the Wnt signaling pathway, a critical pathway involved in cell differentiation, stem cells, and development. Alterations in Wnt signaling is often detected in cancer cells.
The specific projects being conducted in my laboratory are focused on the following questions:
1. Is the activity of the Wnt signaling protein b-catenin altered in folate deficient cells?
2. Do the levels of particular Wnt signaling proteins change in folate deficient cells?
3. Is promoter activity of certain folate sensitive genes, including WNT5a and DKK-1, altered in folate deficient cells?
4. What transcription factors are required for maximal promoter activity of the WNT5a, DKK-1, and EphB6 genes?
5. What identified transcription factors are responsive to folate levels?
Barrett KD, DeMiranda D, Katula KS. (2002) Cyclin B1 promoter activity and functional cdk1 complex formation in G1 phase of human breast cancer cells. Cell Biology International 26: 19-28.
Katula KS, Fields AP, Apple P, Rotruck T. (2002) Cell cycle specific changes in the human cyclin B1 gene regulatory region as revealed by response to trichostatin A. Archives of Biochemistry and Biophysics 401: 271-276.
Katula KS, Atkinson JW, Radewicz A. (2005) Relative abilities of dietary comounds to modulate NF-kB activity as assessed in a cell based reporter system. Journal of Medicinal Foods 8: 269-274.
Katula KS, Heinloth AN, Paules RS. (2007) Folate deficiency in normal human fibroblasts leads to altered expression of genes primarily linked to cell signaling, the cytoskeleton and extracellular matrix. Journal of Nutritional Biochemistry 18: 541-552.
Principles of Biology I (BIO 111)
Cell Biology (BIO 355)
Cell Biology Lab (BIO 356)
Epigenetics (BIO 549)
Cell Cycle and Cancer (BIO 586)
Workshops in Biotechnology (BIO 597)
Molecular Biological Approaches in Research (BIO 596)