Development and Wound Repair
Under control non-pathologic conditions cells repair wounds and embryos develop using many of the same signaling systems. Paramount to this is the proper deposition and formation of extracellular matrix, which is a combination of protein and polysaccharides, for cells to migrate along and communicate with other cells. Therefore repair is often modulated if the proper signal systems are disrupted. In the same light, embryonic development is a highly regulated sequence of events, and changes in the regulation of matrix, associated growth factors or signaling proteins produces abnormalities that clinically produce specific pathologic conditions.
Research in the Department of Biochemistry has evolved from the study of extracellular matrix molecules, signaling molecules and the interaction/regulation of growth factors. As a result, several members of our faculty have research programs that address either the underlying rational for cell reorganizations during Xenopus gastrulation or the activation of signaling mechanisms that are generated with injury and how they are modified by the underlying extracellular matrix.
Wound Repair
Repair of an injury covers a large span of time including the rapid signaling events that are generated, scavenging of debris, inflammation, cell-cell signaling communication that occurs to induce migration, and the synthesis and formation of an extracellular matrix. The latter may be provisional at first and then be followed over months by changes in regulation as has been shown to occur with collagen and proteoglycans. Repair can be studied as a response to an over or underregulation of proteins that may result in a disorganized matrix that damage normal tissue or organ function. Toward this end, investigators in the Department of Biochemistry study migration and repair in cardiovascular disease, Ca2+ signaling, migration and activation of growth factors in corneal wound repair, changes in proteoglycan composition and associated collagen organization and matrix compositional changes in diseases such as Amyloid. Specific areas of interest include collagen synthesis and organization, cell migration, purinergic signaling, and heparin sulfate proteoglycans.
Embryonic Development
Directed cell migration plays a critical role in embryonic development. To migrate in a directed way, a cell must be able to detect and move towards a source of an attractive signal (chemoattractant) or away from a repulsive one. This requires the creation of spatially asymmetrical signaling that leads to extension of leading edge protrusions such as lamellipodia, the generation of traction and force, and a balance of detachment and attachment to neighboring cells and the extracellular matrix. Thus, there is a constant need for the cell to coordinate a variety of extracellular and intracellular activities both spatially and temporally. The challenge is to understand how the cell compartmentalizes, yet cooperatively couples, these activities to drive directed cell movement and how upstream signaling controls this behavior. Toward this end investigators in the Department of Biochemistry study growth factor signaling that is modulated by specific extracellular matrix proteins, and induces specific changes in cellular architecture. In vivo and 3-dimensional ex vivo models are studied in which growth factor signaling and downstream effectors are modulated through introduction of mutant forms, and resultant morphology and cell migration are analyzed.
Faculty involved in conducting research in these areas:
