Overview: Membrane Lipid Biology and Hemoglobinopathies

Our research group studies aspects of membrane lipid organization and their relation to health and disease. The proper lipid composition and organization, essential for the function of plasma membranes, is maintained by a complex system of enzymatic and signal transduction pathways. Our long-term goal is to understand how the molecular structure of the proteins involved, as well as their interaction with each other and with their lipid environment, determines membrane lipid organization. We study the membranes of red cells and their precursors, and we have shown that membrane lipid organization in hemoglobinopathies such as sickle cell anemia and thalassemia can be markedly different. These alterations play an important role in the pathology of these disorders. The abnormal red cell membrane interacts differently with endothelial cells, either directly or by processes in which inflammatory mediators and other signaling compounds play a role. For our studies, we use human samples, and blood and tissue from murine models for thalassemia and sickle cell disease (SCD). These models have proven to be very useful for studies to understand red cell pathology at the molecular level, and for the evaluation of treatment strategies.

By understanding the molecular basis for the maintenance of membrane lipid organization, and the resulting abnormal cellular interactions, we will be able to design strategies relevant to the treatment of disorders associated with altered plasma membranes.