Dr. S. Raza Shaikh will receive the 2012 ISSFAL Early Career Award in Vancouver at the 10th ISSFAL Biennial Congress. Dr. Shaikh will present the following during the Congress: N-3 fatty acids and membrane microdomains: From model membranes to lymphocyte function
ABSTRACT: Eicosapentaenoic (EPA) and docosahexaenoic (DHA) acid are bioactive n-3 polyunsaturated fatty acids abundant in fish oil. These fatty acids have emerging utility for the treatment of chronic inflammation; however, a major limitation toward translating EPA/DHA into the clinic is an incomplete understanding of their molecular mechanisms. One mechanism by which these fatty acids exert their functional effects is by disrupting the biophysical organization of plasma membrane lipid microdomains (i.e. signalosomes, rafts, caveolae). This mechanism is of significance since the plasma membrane regulates most downstream effects of EPA/DHA. We investigated how EPA/DHA target the molecular organization of lipid microdomains in several model systems (model membranes, cell culture, and animal studies) using a combination of spectroscopic, biochemical and quantitative imaging methods. Our initial model membrane studies established that the unique molecular structure of DHA, compared to other fatty acids, served to disrupt membrane microdomain organization by avoiding steric interactions with cholesterol. Subsequent studies using cell culture and mouse models showed DHA, but not EPA, increased the size and molecular order of B cell lipid microdomains, induced by cholera toxin cross-linking. DHA also disrupted the clustering of specific proteins on the micro- and nanometer size scales. Finally, we determined the downstream functional consequences of disrupting B cell lipid microdomains. B cells isolated from mice fed fish oil or treated with fatty acids in vitro suppressed antigen presentation to transgenic T cells, a potential therapeutic target in the inflammatory response. Taken together, our data suggest a model in which DHA, more than EPA, disrupts the size and order of lipid microdomains in order to modulate B lymphocyte function.
Dr. S. Raza Shaikh is an Assistant Professor in the Department of Biochemistry & Molecular Biology and a member of the East Carolina Diabetes and Obesity Institute at East Carolina University. He received his B.S. in Biology/Psychology from Purdue University in 1998. Raza joined the lab of Dr. Bill Stillwell in 1999 where he studied how n-3 fatty acids disrupted lipid microdomain organization in model membranes. He completed his Ph.D. in Biophysics from Indiana University in 2004 and pursued a postdoctoral fellowship in cellular immunology at The Johns Hopkins University from 2004-08. As a post-doctoral fellow, he established how different fatty acids suppressed the function of B cells by targeting plasma membrane molecular organization in the lab of Dr. Michael Edidin. Raza started his faculty position as an Assistant Professor in 2008. He has published a total of 23 research articles, 7 invited review articles, and co-authored 2 book chapters. He is currently funded by the NIH to determine how n-3 fatty acids suppress chronic inflammation by disrupting plasma membrane organization of antigen presenting cells. He is also funded by Stealth Peptides to study how Bendavia disrupts the molecular organization of the inner mitochondrial membrane in a diabetes model.