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J.
David
Castle
Degree(s): Ph.D. Graduate School: Rockefeller University Primary Appointment: Professor of Cell Biology Research Interests: Regulation of Membrane Recycling and Protein Secretion Email Address: jdc4r@virginia.edu |
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Biomedical Sciences Graduate Program(s) Research Description
The main interests of my laboratory are in mechanisms of membrane trafficking
involved in cell secretion and endocytosis. We are using molecular, cell biological
and biophysical approaches to study the pathways of protein secretion in regulated
secretory cells and to explore the function of specific membrane proteins in exocytosis
and in internalization and recycling of cell surface proteins, including growth
factor receptors. Our studies are focused on two families of proteins -- one discovered
by us called SCAMPs (for Secretory Carrrier Membrane Proteins) and the other the
cell surface SNAREs (for SNAP Receptors) that regulate membrane fusion at the
plasma membrane. SCAMPs are evolutionarily conserved, and we have now identified
mammalian isoforms in most membranes that function in intracellular membrane trafficking.
Work in progress suggests that selected SCAMPs may function at a late step of
exocytosis as studied in neuroendocrine and mast cells while other SCAMPs appear
to interact with the Epidermal Growth Factor Receptor following ligand binding
in fibroblasts and may contribute to its internalization and down regulation.
Our evidence also points to molecular interactions between the SCAMPs and SNAREs
as well as other proteins that function in controlling membrane fusion and recycling.
Ongoing collaborations include analysis of SCAMP structure and interactions with
inositol phospholipids with David Cafiso's laboratory in the Department of Chemistry
and real-time analysis of exocytosis in single cells with Gabor Szabo's laboratory
in the Department of Molecular Physiology and Biological Physics. While the majority
of our studies are focused on understanding the roles of these proteins in the
physiological control of membrane and molecular trafficking, they serve as a basis
for future consideration of dysregulation of secretion and trafficking that are
relevant to various diseases including cancer and diabetes. |