A major focus of research in my laboratory concerns the regulation of interactions between the plasma membrane and the actin cytoskeleton, particularly in epithelial cells. The attachment of membrane proteins to actin filaments that lie just beneath the plasma membrane is controlled by various signal transduction pathways, and plays important roles in determining overall membrane physiology as well as cell shape, attachment, and motility.

Biochemical analysis of ezrin, a major membrane-cytoskeletal linking protein in placental microvilli, has led to the identification of a multimeric cytoskeletal protein complex that contains a protein termed CLIC5. CLIC5 is one member of a recently described protein family termed CLIC (chloride intracellular channel). While several existing lines of evidence suggest that these proteins have the capacity to function as chloride ion channels in membranes, their primary cellular and molecular functions are not well established. It is likely that these proteins have important biological implications that relate to human health because CLICs are conserved among vertebrate and invertebrate species and have been implicated in a variety of fundamental cellular processes including chloride ion transport, signal transduction, cell differentiation, epithelial tube formation, cytoskeletal organization, cell division, apoptosis and response to cellular stress. Furthermore, recent studies have shown that CLIC5 is necessary for hearing and balance in mice.

To date, the human CLIC family consists of six distinct genes with several splice variants. Inherent to the study of new gene families is the potential for functional redundancy, which can complicate interpretation of experiments in organisms or individual cells expressing multiple family members. Invertebrate organisms, such as the fruit fly (Drosophila melanogaster) and worm (Caenorhabditis elegans), have proven to be extremely powerful systems to decipher the functional significance of many human gene families. In collaboration with Dr. Soichi Tanda in the Department of Biological Sciences at Ohio University, we are taking advantage of Drosophila as a model system to investigate the biological significance and cellular function of CLICs. A major reason for choosing this organism is that it has only a single CLIC-like gene, thereby minimizing functional redundancies that can hinder progress in understanding CLIC function in vertebrates. Thus, a new avenue of research is to investigate the cellular and biochemical function of the Drosophila CLIC with the ultimate goal of understanding how CLICs function in vertebrates and how these proteins relate to human disease.