Robert H. Edwards
University of California, San Francisco
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Primary Section: 23, Physiology and Pharmacology Secondary Section: 24, Cellular and Molecular Neuroscience Membership Type:
Member
(elected 2017)
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Biosketch
Robert Edwards is a neuroscientist known for his work on the molecular and cellular basis of neurotransmitter release. Using selection in the neurotoxin MPP+, he identified the vesicular monoamine transporters, the first proteins shown to transport classical neurotransmitters into synaptic vesicles. He subsequently identified transporters for the major transmitters GABA and glutamate, and continues to work on their mechanism, regulation and physiological roles. In the course of this work, he has identified mechanisms that contribute to synaptic vesicle filling and helped to elucidate the phenomenon of neurotransmitter corelease, showing that different synaptic vesicle recycling pathways generate synaptic vesicles with different properties. He has also helped to elucidate cellular machinery involved in the production of dense core vesicles, which mediate the release of polypeptides. The work has implications for behavior and neuropsychiatric illness, in particular Parkinson’s disease. His work on alpha-synuclein has provided basic, functional understanding of this protein central to neurodegeneration. Robert Edwards was raised in New York City, attended Yale College and Johns Hopkins Medical School. He trained in clinical neurology, studied as a postdoctoral fellow with William J. Rutter at UCSF and joined the faculty at UCLA in 1990 before returning to UCSF in 1995.
Research Interests
We wish to understand how neurotransmitter release contributes to information processing by the nervous system. We study the basic properties of release: vesicle filling, regulation of exocytosis, the fusion pore and recycling/biogenesis. With regard to neurotransmitter uptake by synaptic vesicles, we focus on the vesicular glutamate transporters and have identified a series of properties that enable vesicle filling despite the large fluctuations in ionic gradients that accompany exo- and endocytosis. We are developing new, electrophysiological tools to study these transporters and pursuing structural approaches to elucidate the mechanisms involved. With regard to exocytosis, we found that synaptic vesicles containing dopamine undergo release with different properties from those releasing glutamate, and study the mechanisms responsible for this dual mode of neurotransmission. We have also found a role for alpha-synuclein at the exocytic fusion pore, providing some of the first functional information about this protein implicated in neurodegeneration. We are now developing assays to determine the structural basis for this activity and explore its role in degeneration. Recently, we also found that different synaptic vesicle recycling pathways contribute to the observed differences in dopamine and glutamate release. We pursue these mechanisms using a combination of live imaging, biochemistry and physiology.
