Overview
We use Drosophila melanogaster as a model to understand nervous system development and function. A genetic screen for molecules important to these processes identified the fly ortholog of the spastin gene, which when mutated in humans leads to a progressive neurodegenerative disease called Autosomal-Dominant Hereditary Spastic Paraplegia (AD-HSP). Individuals with AD-HSP have difficulty walking, sometimes from as early as childhood, and can end up confined to wheelchairs. We have shown that loss of spastin in the fly larva compromises motoneuron function, while adults exhibit weak legs and do not fly. Spastin is a member of the AAA family of ATPases, and functions by severing microtubules into smaller segments. Our results indicate that the absence of spastin function in mutant flies leads to a reduction in microtubule content at synaptic boutons, presumably causing the weakened neurotransmission. Among our goals in the lab are to understand how this happens at a cell-biological level, and to examine specific phenotypes associated with mutations mimicking those found in the human disease. Using Drosophila as a model system allows us to rapidly generate flies with any number of specific mutations, and then study the consequences of these mutations at the biochemical, cell biological, developmental, electrophysiological and behavioral levels.
Current Appointments & Affiliations
Associate Professor of the Practice of Biology
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2014 - Present
Biology,
Trinity College of Arts & Sciences
Assistant Research Professor in Molecular Genetics and Microbiology
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2011 - Present
Molecular Genetics and Microbiology,
Basic Science Departments
Associate Research Professor of Cell Biology
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2022 - Present
Cell Biology,
Basic Science Departments
Faculty Network Member of the Duke Institute for Brain Sciences
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2011 - Present
Duke Institute for Brain Sciences,
University Institutes and Centers
Associate of the Duke Initiative for Science & Society
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2017 - Present
Duke Science & Society,
University Initiatives & Academic Support Units
Recent Publications
Suppression of spastin Mutant Phenotypes by Pak3 Loss Implicates a Role for Reactive Glia in AD-HSP.
Journal Article Frontiers in neuroscience · January 2020 Neurodegenerative mechanisms due to mutations in spastin currently center on neuronal defects, primarily in microtubule and endomembrane regulation. Spastin loss in Drosophila larvae compromises neuronal microtubule distribution, alters synap ... Full text CiteDrosophila Models of Hereditary Spastic Paraplegia
Chapter · January 1, 2015 Hereditary spastic paraplegia (HSP) is a debilitating movement disorder with no prevention, no cure, and few options for symptom management. Rapid and relevant information is required, and the model organism Drosophila melanogaster can contribute significa ... Full text CiteCold temperature improves mobility and survival in Drosophila models of autosomal-dominant hereditary spastic paraplegia (AD-HSP).
Journal Article Disease models & mechanisms · August 2014 Autosomal-dominant hereditary spastic paraplegia (AD-HSP) is a crippling neurodegenerative disease for which effective treatment or cure remains unknown. Victims experience progressive mobility loss due to degeneration of the longest axons in the spinal co ... Full text CiteRecent Grants
Cell and Molecular Biology Training Program
Inst. Training Prgm or CMEMentor · Awarded by National Institutes of Health · 2021 - 2026Transmission electron microscope (TEM)
EquipmentMinor User · Awarded by National Institutes of Health · 2019 - 2021Genetics Training Grant
Inst. Training Prgm or CMEMentor · Awarded by National Institutes of Health · 1979 - 2020View All Grants
Education, Training & Certifications
Duke University ·
1998
Ph.D.
University of California, San Diego ·
1990
B.S.