The research in this laboratory addresses the question of the role of lipid bilayer membrane structure in transmembrane transduction of biological signals. A variety of biological stimuli (e.g., hormones, growth factors, antigens) act via a pathway involving increased lipid metabolism. The products of the increased lipid metabolism, such as diacylglycerol (DAG) and ceramide, serve as intracellular "second messenger" activating such membrane-associated enzymes as protein kinase C and phospholipases and resulting in the biological response of the cell to the original stimulus. We are studying molecular details of DAG- and ceramide-induced activation of these enzymes using a variety of biophysical and biochemical techniques including nuclear magnetic resonance, delayed luminescence spectrophotometry and specific enzymatic assays. The obtained information allows us to predict cellular responses to specific membrane perturbations, and can be used in selecting/designing agents (drugs) with the potential of modifying this response in a number of pathological conditions. We are also studying intracellular pathways utilized by exogenous factors to effect cellular biological response, primarily in brain endothelial cells and astrocytes. The specific questions studied include the role of activation of brain endothelial cells by HIV-derived protein, tat, in AIDS dementia, and mechanism of brain endothelial cell activation by cytokines and nicotine leading to ischemic stroke.
Raphael Zidovetzki
Professor of Cell Biology & Neuroscience

Current Lab Members

Don Armstrong
Graduate Student: Cell Molecular and Developmental Biology