Studies in the Pagano laboratory are focused on the intracellular trafficking of sphingolipids and cholesterol in normal and disease cell types. See http://mayoresearch.mayo.edu/mayo/research/pagano_lab/.

Although elevated serum cholesterol is known as a major risk factor for cardiovascular disease and stroke, the regulation of cholesterol homeostasis has much broader health implications. Abnormalities in intracellular cholesterol distribution or storage have been implicated in a number of neurodegenerative disorders including Alzheimer disease, Parkinson disease, and multiple lipid storage diseases (e.g., Niemann Pick Type C and GM1 gangliosidosis). Studies in our laboratory have demonstrated extensive interactions between cholesterol and sphinoglipids which may be responsible for defects in cellular functions in some of these diseases. For example, we found that cells from patients with various lipid storage diseases (e.g., Niemann Pick Type C) exhibit defective intracellular transport of membranes due to accumulation of cholesterol and other lipids. Importantly, over-expression of certain proteins (called Rab GTPases) within these cells "corrected" this defective membrane trafficking and also resulted in a dramatic lowering of stored cholesterol. We now seek to better understand the mechanism by which Rab over-expression lowers stored lipids, and to further explore the concept that modulation of intracellular transport may be a new therapeutic approach for the treatment of diseases in which lipid homeostasis is impaired.

Other studies in the lab are focused on the cholesterol and sphingolipid-dependent endocytosis of certain lipids and proteins at the plasma membrane. These endocytic mechanisms may play important roles in the infectivity of certain pathogens and in cell-cell interactions.