Molecular mechanisms regulating cell growth, differentiation, and cancer progression with a focus on the Wnt cell signaling pathway and gene regulation.
Ph.D., Northwestern University
Earlier research in my lab was focused on the transcriptional regulation of human cyclin B1 gene expression during the S/G2 phase of the cell cycle and the effects of nutrients of gene expression. One of our funded projects was to investigate changes in gene expression and cell signaling that result from reduced levels of cellular folate. The goal of this project was to provide a mechanistic understanding of the link between folate deficiency and various human conditions, including cancer and developmental defects. We 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 functioned 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.
The results of these studies lead to our current interest in WNT5A. WNT5A is a secreted protein that binds to cell surface receptors and activates cell signaling pathways that are critical in morphogenesis, cell differentiation, and tissue homeostasis. Importantly, WNT5A is often misregulated during cancer progression. We use cell culture to investigate WNT5A function and regulation during osteogenesis (bone development) and colorectal cancer cells.
Some of the questions we are addressing include:
Bhandari D, Elshaarrawi A, Katula KS (2021) The human WNT5A isoforms display similar patterns of expression but distinct and overlapping activities in normal human osteoblasts. J Cell Biochem 122, 1262-1276. doi: 10.1002/jcb.29950.
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.
Katula KS, Joyner-Powell NB, Hsu CC, Kuk A. (2012) Differential regulation of the mouse and human Wnt5a alternative promoters A and B. DNA Cell Bio 32, 1-13
Vaidya H, Rumph C, Katula KS (2016) Inactivation of the WNT5A alternative promoter B is associated with DNA methylation and histone modification in osteosarcoma cell lines U2OS and SaOS-2. PLoS One 11(3): e0151392.
Principles of Biology I (BIO 111)
Cell Biology (BIO 355)
Cell Biology and Genetics Lab (BIO 375)
Epigenetics (BIO 587)
Cell Cycle and Cancer (BIO 586)
Molecular Biological Approaches in Research (BIO 596)