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Role of intracellular signaling lipids in membrane trafficking in normal and diseased neurons.
Lipid-mediated signaling regulates a plethora of cellular processes, including organelle trafficking, signal transduction and cytoskeletal dynamics. Consistent with a central role of intracellular regulatory lipids in cell physiology, dysregulation of their metabolism has been implicated in a growing number of diseases, including neurodegenerative disorders. Research in my laboratory focuses on the analysis of major bioactive phospholipids, such as phosphoinositides and phosphatidic acid, and their role in the regulation of membrane trafficking to and from the plasma membrane as well as along the endolysosomal and autophagy pathways. We study intracellular lipid signaling primarily in neurons in order to understand the molecular and cellular mechanisms controlling normal synaptic function. We also study how perturbations in such signaling can lead to synaptic malfunction, neurodegeneration and cognitive decline in Down syndrome and Alzheimer's disease. To tackle these fundamental questions, we employ multidisciplinary approaches, which range from molecular and cell biology, protein and lipid biochemistry (including 'lipidomics') to mouse genetics and behavioral assessments of genetically-modified mice.
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