Our current research interests are focused on the structure and dynamic membrane interactions in abnormal nerve myelin, in which alterations have resulted from experimental, pathological, or genetic conditions. To link structure and composition at the molecular, macromolecular and tissue levels in the nervous system, our studies in these areas have utilized x-ray diffraction, microscopy at the light and ultrastructural levels, a variety of protein and lipid biochemical techniques, and molecular modeling.
What holds myelin together, and how are its constituents targeted in diseases? To characterize the molecular organization of lipids and proteins in nerve myelin membranes, and to define the molecular interactions of its membrane arrays, we have correlated biophysical and biochemical results from different types of specimens (e.g., whole unfixed or fixed tissue from a phylogenetic range of vertebrates, tissue homogenates, tissue fractions and model lipid/protein systems). Among the questions we addressed were: how does the organization of proteins and lipids in myelin account for the inter-membrane interactions of the membranes? What is the structural basis of demyelination? Our findings are relevant to understanding the process of membrane disruption and delamination which occurs in demyelinating diseases such as multiple sclerosis and certain peripheral neuropathies. Our findings have also helped to explain how specific mutations in myelin adhesion proteins or in lipid biosynthetic pathways affect the stability and functionality of the myelin.