Research & Publications
Central to the integrated function of multicellular organisms is cell contact mediated signaling and the spatial organizations of specialized membrane-surface domains. While many factors contribute, recent evidence indicates that the spectrin based membrane skeleton plays a pivotal role in these processes. Current research in the laboratory is aimed at understanding three aspects of the spectrin membrane skeleton in erythrocytes, epithelial cells, and neurons: 1) The factors that mediate its polarized assembly with specific surface membrane receptor domains; 2) the nature of the proteins that interact with spectrin and their role in signal transduction, cell differentiation, vesicle trafficking, and topographic membrane assembly; and 3) the molecular basis of diseases that involve spectrin or any of its associated proteins, including contributions of the cortical cytoskeleton to the phenotypic alterations of malignant cells and the molecular pathology of acquired and inherited disorders involving this structure. Our studies on the erythrocyte focus on a molecular understanding of how specific proteins that cause human disease.
Specialized Terms: Hemolytic Disease; Degenerative Brain Disease; spectrin; Autopsy Pathology; Renal Pathology; Medical Informatics; Computer Aided Instruction (CAI); Telepathology
Extensive Research Description
Our research focuses on understanding the structure and function of the spectrin-ankyrin-actin cytoskeleton and the mechanisms by which it mediates membrane receptor and adhesion-complex organization; signal transduction; and vesicle trafficking from the ER to the plasma membrane. Our recent studies implicate a major and unexpected role for the spectrin skeleton in the pathways of vesicle trafficking and membrane assembly. In parallel studies we are seeking to understand the molecular basis of diseases arising from aberrant cytoskeletal function. Studies are carried out both in vitro utilizing functional and biophysical assays; in cell culture using genetically modified systems; and in transgenic animals. Areas of special interest include organization of the plasma membrane in erythrocytes; vesicle trafficking and the establishment of polarity in epithelial cells; and the control of receptor organization at the synapse.
Autopsy; Computer-Assisted Instruction; Medical Informatics; Pathology; Spectrin; Telepathology