Drugs, hormones, and other ligands attach to and activate receptors on or inside the cell to elicit responses. These responses could be tissue growth through cell division, differentiation into a different cell or tissue type, or programmed cell death which we call apoptosis. All of these normal responses are important for the maintenance of the healthy human body. When these responses become severely altered, it may result in cancer.
This project, being led by Dr. Daniel Lundberg, Dr. Raymond Merritt, and Dr. Derek Braun, focuses on two groups of cellular proteins: the protein kinase C (PKC) family and the Ras guanyl nucleotide releasing factors, or RasGRPs. PKCs and RasGRPs constitute important signaling pathways in cellular biology, and mutations in these pathways cause inappropriate cell division, leading to cancer.
We are collaborating with Dr. Peter M. Blumberg, a widely respected scientist at the National Cancer Institute, NIH, to study the PKCs and RasGRPs. In the Molecular Genetics Laboratory, we are using site-directed mutagenesis to create mutated versions of RasGRP isoforms, which we then purify and test for their affinities to synthesized drugs. The molecular genetics is all being performed in our laboratory at Gallaudet University, and the radioligand binding assays, confocal microscopy, and cell culture experiments are being performed at the National Cancer Institute.
The longer term goals of this project are to not only train students by performing research alongside them, but also to develop novel strategies for manipulating the signaling pathways that involve PKC and RasGRPs.