Suzanne Pfeffer

Our lab seeks to understand the molecular basis of inherited Parkinson's Disease.  Activating mutations in the LRRK2 kinase cause Parkinson's , and the major substrates of LRRK2 kinase are a subset of proteins called Rab GTPases.  Together with our collaborators, we have discovered that phosphorylation of Rab proteins completely changes the partner proteins with which they interact and leads to a blockade in the formation of critical signaling structures called primary cilia.  We are using biochemical, cell biological and genome-wide approaches to study the molecular cell biology of Parkinson's Disease by focusing on the consequences of Rab GTPase phosphorylation.  Our work includes single molecule biochemical experiments to undertstand the kinase and its corresponding phosphatase--how they are recruited to membranes and activated.  We also study LRRK2-mediated loss of cilia in specific neuronal cell types and astrocytes in both mouse and human brains.  We are using state of the art microscopic tools to understand why cilia are lost and how this leads to Parkinson's disease.