Elected to second term as Associate Director of Research and Doctoral Universities Constituency of Sigma Xi, The Scientific Research Society.
The Role of Molecular Structure in Determining Physical and Biological Properties of Proteins and Small Ligands
The research in my laboratory is directed at understanding the role of posttranslational modifications on a central nervous system protein present in the myelin membrane. This protein known as the myelin basic protein (MBP) is known to be extensively posttranslationally modified by phosphorylation, methylation, and deimination. In addition, the protein binds Zinc, copper and other metal ions. Many of these modifications are known to be involved in a number of human pathologies of which the most well known one is multiple sclerosis. My laboratory studies the presence of these posttranslational modifications in MBP, identifies the amino acids that are modified, and if that modification is involved in the aberent behavior of the membrane. One extreme example of this occurs in a severe form of Multiple Sclerosis in which the amino acid arginine present in MBP is converted into the amino acid citrulline. In MBP there are 19 arginine residues and in the form of MS known as Marburgs disease, 18 of the 19 arginine residues are converted into citrulline. This removes 18 positive charges from the protein and must result in a change in coformation and in its ability to function normally thereby permitting attacking on the membrane by the immune system. We study the changes in the MBP using mass spectrrometry, Circular Dichroism, NMR, FTIR and other spectroscopic techniques.
Another area of MBP interest is how it has changed in primary structure through evolution. Once the sequence of MBP from a particular species has been identified It can be analyzed relative to its position in the evolutionary chain. This also allows for an assessment of the posttranslational modifications and the primary structure.
Myelin Basic Protein and Multiple Sclerosis: Spectroscopic and chemical assessment of structure of MBP, postranslational modifications, evolution, role in Multiple Sclerosis and Experimental Allergic Encephalomyelitis.