Andrew P. Lieberman, MD, PhD
Our laboratory studies inherited neurodegenerative diseases, with the goal of understanding the mechanisms underlying neurological dysfunction so as to develop effective treatments. We are particularly interested in the CAG repeat diseases, a group of nine genetically related disorders caused by expanded CAG/glutamine tracts in the coding regions of disease-causing genes. Among these disorders is Kennedy disease, a degenerative disease that predominantly affects lower motor neurons and is caused by a mutation in the androgen receptor gene. We use genetic and biochemical approaches to understand the mechanisms by which the mutant androgen receptor causes the selective neuronal degeneration that is characteristic of this disorder and to test novel therapeutic approaches. Our studies also focus on Niemann-Pick type C disease, an autosomal recessive neurovisceral lipid storage disease for which there is no cure. Most cases of this disease are caused by mutations in the NPC1 gene, and result in a clinically heterogeneous disorder characterized by devastating neurodegeneration, often in childhood. Loss of NPC1 function disrupts intracellular lipid trafficking and causes the predominant accumulation of glycosphingolipids within neurons. The pathways leading from disrupted intracellular lipid trafficking to neurodegeneration are poorly understood. We use cellular and mouse models of Niemann-Pick type C disease to address these questions and to uncover therapeutic targets.