Investigating Fer Kinase Regulation of Gene Transcription During Development
Dr. Aaron Putzke
The Caenorhabditis elegans protein FRK-1, an ortholog to Zebrafish (Danio rerio) and mammalian Fer kinase, is critical to the proper embryonic and larval development. In humans, aberrant Fer kinase levels have also been implicated in the progression of leukemia and prostate cancer. In addition to roles in the formation of the hypodermis in C. elegans, FRK-1 has been shown to localize to the nucleus in a cell-cycle dependent manner (Putzke et al, 2005.). This localization has led us to hypothesize that FRK-1, and its ortholog Fer kinase, are involved in the regulation of transcription factors during development. To discover potential gene targets regulated by Fer kinase activity, we aim to perform microarray analysis in nematodes, Zebrafish and human cells in the absence of Fer/FRK-1. Our microarray results, thus far, indicate that many genes with abnormal levels of transcription at 24 and 48 hours post fertilization in Danio rerio are associated with proper neurogenesis and vasculogenesis of the Zebrafish. We are currently pursuing microarray data in C. elegans (genomic knockout ok760) and as well as a human cell line utilizing with Fer knock-down (via siRNA). The aim of this research is to determine more about the development of C. elegans and Danio rerio, and to identify potential therapeutic gene targets for treatment in human cancers.
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