David Harris

My laboratory investigates the molecular and cellular mechanisms underlying two classes of human neurodegenerative disorders: prion and Alzheimer’s diseases.  Alzheimer’s disease afflicts 5 million people in the U.S., a number that will increase dramatically as the population ages.  Prion diseases are much rarer, but are of great public health concern because of the global emergence of bovine spongiform encephalopathy (“mad cow disease”), and its likely transmission to human beings.  Moreover, prions exemplify a novel mechanism of biological information transfer based on self-propagating changes in protein conformation, rather than on inheritance of nucleic acid sequence.

Our work has two broad objectives. First, we wish to understand how prions and other misfolded protein aggregates cause neurodegeneration, neuronal death and synaptic dysfunction.  In this regard, we seek to identify what molecular forms of PrP and the Alzheimer’s Aβ peptide represent the proximate neurotoxic species, and what receptors and cellular pathways they activate that lead to pathology.  Second, we aim to use our knowledge of the cell biology of prion and Alzheimer’s diseases to develop drug molecules and other therapeutic modalities for treatment of these disorders.