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Research Description:
My laboratory utilizes biochemical and genetic approaches to study central problems in cell biology such as signal transduction and cell motility. Below I describe several examples of current interests in the lab:
1. Understanding the molecular mechanism of cell movement. The ability of cells to migrate plays a central role in many normal biological processes including embryonic development, the cell-mediated immune response, and wound healing. The uncontrolled motility of cells is a hallmark of the deadliest cancers. It has been clear for some time that cell migration depends on the ability of cells to adhere to the underlying substratum and to extend the cell surface in the direction of movement. Our lab has identified components of the machinery that regulates cell motility. We are currently employing biochemical and genetic studies in the mouse and the fruitfly to analyze the physiological roles of the motility machinery for development and for normal cell function.
2. Signaling from the cell surface to the nucleus. Cell adhesion to specific molecules in the extracellular environment can trigger a variety of physiological responses including changes in gene expression and cell proliferation. We are interested in understanding how cell adhesion events at the cell surface can affect processes that depend on the activity of the cell nucleus. We have recently identified a protein that can shuttle between the nucleus and sites of cell adhesion, suggesting a possible mechanism for communication between these spatially segregated cellular compartments.
3. Integration of signal transduction pathways. One of the major challenges for cell biologists over the past decade has been to elucidate the mechanism by which transmembrane signaling occurs. We now understand a great deal about how ligands such as growth factors influence cell behaviors such as locomotion, proliferation and gene expression, by binding to cell surface receptors. A new frontier in the area of signaling is the molecular how the cell integrates information from multiple receptors to achieve the appropriate response. We are using mammalian cell culture systems and genetic approaches to tackle this problem. Recently, we have focused our efforts on an adaptor protein called PINCH. PINCH has properties that suggest it could participate in the coordination of signals coming simultaneously from multiple types of cell surface receptors.
4. Establishment and maintenance of the contractile machinery of muscle cells. Muscle is required for the function of many central systems in mammals including the locomotory, circulatory, respiratory, urogenital, and digestive systems. We have utilized both biochemical and genetic approaches to study muscle development, structure, and function. We have identified and characterized several proteins that play pivotal roles in muscle. One class of proteins is expressed exclusively in smooth muscle; we are exploring the role of this group of proteins in vasculogenesis, a process that depends on smooth muscle function. If these proteins are essential for blood vessel development or function, they may serve as targets for development of therapeutic agents to perturb angiogenesis. We have also recently identified a structural element of the muscle cytoarchitecture that appears to play a role in stabilizing the contractile apparatus. We are currently examining the possibility that loss of function of this protein is responsible for an inherited form of human muscular dystrophy.
Research Keywords:
Cell Adhesion, Signal Transduction, Cell Migration, Cytoskeleton, Muscle Development