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Gwenn Garden, M.D., Ph.D.

Professor of Neurology
Research Affiliate, Center on Human Development and Disability
University of Washington
Box 356465
Seattle, WA 98195-6465

Gwenn Garden, M.D., Ph.D.

Dr Garden’s research program involves two major projects. The first focuses on molecular regulation of neuroinflammation. Microglia are resident CNS inflammatory cells that respond to acute and chronic neural injury. When microglia are activated, they may adopt a variety of responses including a neurotoxic response involving the release of inflammatory cytokines and neurotoxic substances or a neuroprotective response that includes the secretion of trophic factors and promotion of tissue repair. The molecular patterns that regulate microglia response patterns are not well understood. Her group has been examining a number of molecular pathways that influence microglia behavior and response patterns. Garden has focused extensively on specific transcriptional regulators that are induced by oxidative stress and microRNAs with demonstrated roles in modulating the behavior of macrophages. The overarching goal of this research program is to identify potential therapeutic targets that could modify the inflammatory response to neural injury by promoting microglia to adopt the neuroprotective as opposed to neurotoxic pattern of response to neural injury.

Garden's second research program is directed toward neurodegeneration in inherited polyglutamine disorders. This program currently focuses on Spinal Cerebellar Ataxia type 7 (SCA7), an autosomal dominant neurodegenerative disorder caused by a CAG repeat expansion within the ataxin-7 gene. The main characteristics of the disorder include ataxia, retinal degeneration and atrophy of the cerebellum and associated brain stem structures. Garden and her group hypothesize that polyglutamine expanded ataxin-7 results in an altered neural environment that specifically affects neurons that are involved in generating postural tone and coordinated movements. The corollary to this hypothesis is that if some or all of the specific components of the altered environment can be corrected, neurological function may improve and neurodegeneration may be prevented in SCA7 patients. Using a conditional knockout model of SCA7, Garden has identified a number of key cellular players in the pathogenesis of neurodegeneration in SCA7. She is currently developing approaches to evaluate transcriptional changes in specific cell types using a variety of advanced methods for isolating cell type specific RNA for global and directed transcriptome analysis.

Gwenn Garden's Department of Neurology webpage

University of Washington • Center on Human Development and Disability • Box 357920 • Seattle WA 98195-7920 USA • 206-543-7701 •