Our lab is interested in how signals from membrane receptors are transduced to the nucleus altering gene expression, cell shape, proliferation and differentiation. We are particularly interested in tyrosine-specific protein kinases in breast and prostate cancer, as well as lymphoma/leukemia. Particular focus of the lab include:1) roles of the EGF receptor family and related molecules HER4/ErbB4 in growth inhibition and differentiation and 2) Mer (a novel receptor tyrosine kinase) and how signals downstream from Mer enhance prostate tumorigenesis.
The Elston lab is interested in understanding the dynamics of complex biological systems, and developing reliable mathematical models that capture the essential components of these systems. The projects in the lab encompass a wide variety of biological phenomena including signaling through MAPK pathways, noise in gene regulatory networks, airway surface volume regulation, and understanding energy transduction in motor proteins. A major focus of our research is understanding the role of molecular level noise in cellular and molecular processes. We have developed the software tool BioNetS to accurately and efficiently simulate stochastic models of biochemical networks
We are characterizing the structural signals that are responsible for moving proteases normally stored intracellularly in lysosomes into the extracellular environment, where they may participate in tumor cell metastasis. One putative mediator of this altered protease targeting is an endosomal integral membrane protein that behaves like a cellular "dirty bomb", undergoing proteolysis which releases fragments that target to various cellular sites where they serve distinct functions. The multiple proteolytic cleavages ultimately release the cytoplasmic tail from the membrane. This tail, which possesses a putative signal for import into the nucleus, can modify other proteins with ubiquitin, which causes them to be degraded rapidly. Proteolysis of the putative receptor is mediated by the same enzymes that cleave the Alzheimer's precursor protein into fragments that can aggregate to form plaques in the brain. When neurite outgrowth is stimulated, expression of this protein is upregulated, suggesting that it also plays a role in development. We are using biochemical characterization of the protein's domain structure to relate its proteolysis, cellular targeting, and signaling to the nucleus to altered targeting of lysosomal enzymes.
The research in my lab is divided into two main areas - 1) Atomic force microscopy and fluorescence studies of protein-protein and protein-nucleic acid interactions, and 2) Mechanistic studies of transcription elongation. My research spans the biochemical, biophysical, and analytical regimes.
Investigation of genes/proteins that play key roles during embryonic and postnatal development of craniofacial/oral/dental structures; and their contribution to normal variation and to congenital and acquired disorders.
