The Pfeffer Lab uses biochemical, cell biological and genome-wide screening approaches to understand the molecular basis of inherited Parkinson's disease. Parkinson’s disease currently affects more than 6 million people worldwide; it occurs upon loss of brain cells that produce dopamine, a neurotransmitter that coordinates movement.

We are pioneers in the study of Rab GTPases that are master regulators of receptor trafficking in cells. The human genome encodes ~65 Rabs; a subset of Rabs are the major substrates of LRRK2 kinase that when mutated (and activated) leads to inherited Parkinson’s Disease. LRRK2-mediated Rab phosphorylation flips a switch: Rabs fail to bind their normal partners and instead bind a new set of proteins. We showed that these new interactions block the formation of primary cilia that are critical signaling structures on cell surfaces. We are studying the molecular and cellular consequences of phosphoRab-specific protein partner interactions and how LRRK2 phosphorylation is regulated by the Rab-specific phosphatase, PPM1H.