Nina T. Sherwood, Associate Professor of the Practice  

Nina T. Sherwood

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, California Institute of Technology, 2005
Ph.D., Duke University, 1998
B.S., University of California at San Diego, 1990

Office Location: Box 90338 137 Bio Sciences, 130 Science Drive, Durham, NC 27708
Office Phone: (919) 684-8658
Email Address: nina.sherwood@duke.edu

Specialties:
Cell and Molecular Biology
Genetics
Neuroscience

Research Categories: Functions of spastin and other microtubule severing proteins in the nervous system; Drosophila models of human disease

Current projects: Analysis of Drosophila models of human AD-HSP, Genetic screen for candidate interactors of spastin, kat60, or kat-like, Cell biology of microtubule regulation by Spastin and other AAA ATPases, Characterization of Spastin function in other fly tissues/stages, Role of microtubule severing in synaptic bouton formation

Research Description: 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.

Areas of Interest:
The role of microtubule severing in the nervous system
Regulation of microtubule severing proteins
Drosophila models of human disease such as AD-HSP
Molecular mechanisms of synapse formation

Recent Publications   (More Publications)   (search)

  1. Ozdowski, EF; Baxter, SL; Sherwood, NT, Drosophila Models of Hereditary Spastic Paraplegia, in Movement Disorders: Genetics and Models: Second Edition, 2nd, edited by Mark S. LeDoux (October, Submitted, 2014), pp. 1103-1122, Elsevier [doi]  [abs] [author's comments].
  2. Baxter, SL; Allard, DE; Crowl, C; Sherwood, NT, Cold temperature improves mobility and survival in Drosophila models of autosomal-dominant hereditary spastic paraplegia (AD-HSP)., Disease models & mechanisms, vol. 7 no. 8 (August, 2014), pp. 1005-1012 [doi]  [abs].
  3. Baxter SL, Allard DE, Crowl C, Sherwood NT, Cold temperature improves mobility and survival in Drosophila Models of Autosomal-Dominant Hereditary Spastic Paraplegia (AD-HSP)., Disease Models and Mechanisms (Submitted, December, 2013)  [abs] [author's comments].
  4. Stewart, A; Tsubouchi, A; Rolls, MM; Tracey, WD; Sherwood, NT, Katanin p60-like1 promotes microtubule growth and terminal dendrite stability in the larval class IV sensory neurons of Drosophila., The Journal of neuroscience : the official journal of the Society for Neuroscience, vol. 32 no. 34 (August 22, 2012), pp. 11631-11642 (Cover Image.) [22915107], [doi]  [abs].
  5. Stone, MC; Rao, K; Gheres, KW; Kim, S; Tao, J; Rochelle, CL; Folker, CT; Sherwood, NT; Rolls, MM, Normal Spastin Gene Dosage Is Specifically Required for Axon Regeneration, Cell Reports, vol. 2 no. 5 (November 29, 2012), pp. 1340-1350 (doi: 10.1016/j.celrep.2012.09.032.) [S2211124712003397], [doi]  [abs].

Lab Website: http://sites.duke.edu/ninasherwoodlab/