Nina Tang Sherwood

Associate Professor of the Practice in the Department of Biology

Office: 
Box 90338 137 Bio Sciences, 130 Science Drive, Durham, NC 27708
Campus Box: 
90338
Phone: 
(919) 684-8658
Fax: 
919-668-3656 Lab phone

Research Interests: 

We use Drosophila melanogaster as a model to understand nervous system development and function. In a genetic screen for molecules important to these processes, we discovered 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. This form of regulation has been shown for only one other protein, katanin, which is closely related to spastin. Our results indicate that the absence of such microtubule severing in spastin mutant flies leads to a reduction in microtubule content at synaptic boutons, presumably causing the weakened neurotransmission. Among our goals in the lab are thus 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 spastin mutations, and then study the consequences of these mutations at the biochemical, cell biological, developmental, electrophysiological and behavioral levels.

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.

Education

  • Postdoctoral Scholar 2005, California Institute of Technology

  • Ph.D. 1998, Duke University

  • B.S. 1990, University of California at San Diego

Papers Published

Cold temperature improves mobility and survival in Drosophila models of autosomal-dominant hereditary spastic paraplegia (AD-HSP)., 8, 2014
Baxter, SL; Allard, DE; Crowl, C; Sherwood, NT, Disease models & mechanisms. 7 vol. (8); pp. 1005-1012

Katanin p60-like1 promotes microtubule growth and terminal dendrite stability in the larval class IV sensory neurons of Drosophila., August 22, 2012
Stewart, A; Tsubouchi, A; Rolls, MM; Tracey, WD; Sherwood, NT, The Journal of neuroscience : the official journal of the Society for Neuroscience. (August 22, 2012) 32 vol. (34); pp. 11631-11642

Normal Spastin Gene Dosage Is Specifically Required for Axon Regeneration, November 29, 2012
Stone, MC; Rao, K; Gheres, KW; Kim, S; Tao, J; Rochelle, CL; Folker, CT; Sherwood, NT; Rolls, MM, Cell Reports. (November 29, 2012) 2 vol. (5); pp. 1340-1350

Loss of Drosophila melanogaster p21-activated kinase 3 suppresses defects in synapse structure and function caused by spastin mutations., 9, 2011
Ozdowski, EF; Gayle, S; Bao, H; Zhang, B; Sherwood, NT, Genetics. 189 vol. (1); pp. 123-135

Functional conservation of human Spastin in a Drosophila model of autosomal dominant-hereditary spastic paraplegia., May, 2010
Du, F; Ozdowski, EF; Kotowski, IK; Marchuk, DA; Sherwood, NT, Human Molecular Genetics. (May, 2010) 19 vol. (10); pp. 1883-1896

Drosophila spastin regulates synaptic microtubule networks and is required for normal motor function, December, 2004
Sherwood, NT; Sun, Q; Xue, M; Zhang, B; Zinn, K, PLoS Biology. (December, 2004) 2 vol. (12); pp. 2094-2111

Long-term regulation of excitatory and inhibitory synaptic transmission in hippocampal cultures by brain-derived neurotrophic factor., 0, 2000
Bolton, MM; Lo, DC; Sherwood, NT, Progress in Brain Research. 128 pp. 203-218

Long-term enhancement of central synaptic transmission by chronic brain-derived neurotrophic factor treatment., 8, 1999
Sherwood, NT; Lo, DC, The Journal of neuroscience : the official journal of the Society for Neuroscience. 19 vol. (16); pp. 7025-7036

Neurotrophin regulation of ionic currents and cell size depends on cell context., 5, 1997
Sherwood, NT; Lesser, SS; Lo, DC, Proceedings of the National Academy of Sciences of USA. 94 vol. (11); pp. 5917-5922

Neurotrophins differentially regulate voltage-gated ion channels., 0, 1997
Lesser, SS; Sherwood, NT; Lo, DC, Molecular and Cellular Neuroscience. 10 vol. (3-4); pp. 173-183

Papers Submitted

Drosophila Models of Hereditary Spastic Paraplegia in 10, 2014
Ozdowski, EF; Baxter, SL; Sherwood, NT

Cold temperature improves mobility and survival in Drosophila Models of Autosomal-Dominant Hereditary Spastic Paraplegia (AD-HSP). in Disease Models and Mechanisms December, 2013
Baxter SL, Allard DE, Crowl C, Sherwood NT