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FRISC: The Faculty Research Interests Science Comparator |
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Associate Professor of Cell Biology
Molecular Biophysics
Neuroscience
Office: (214) 648-0289
Laboratory: (214) 648-0297
FAX: (214) 648-9469
Email: Brady03@utsw.swmed.edu
Meteorin: a secreted protein that regulates glial cell differentiation and promotes axonal extension.
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Score: 0.464 |
The neuron represents a unique model for addressing fundamental questions in cell and
molecular biology. The size, shape, and specialized functions of neurons permit analyses
of cell differentiation and intracellular dynamics. Our research addresses four areas: 1)
Molecular Mechanisms of Axonal Transport; 2) Specialization of the Neuronal Cytoskeleton;
3) Glial Modulation of Neuronal Function; and 4) Effects of Physiological Stress on
Neurons. These studies illuminate mechanisms underlying neuronal function, regeneration,
pathogenesis in neurodegenerative diseases, and neuronal responses to environmental
factors or in diseases such as multiple sclerosis.
Neuronal and nonneuronal cells require ordered transport and targeting of membrane
organelles. We discovered a new class of mechanochemical enzymes, kinesins, which serve as
motors for organelle transport. Current research addresses basic questions regarding the
cell and molecular biology, biophysics, and neurobiology of the kinesins. Projects include
expression of kinesin isoforms; mutagenesis of kinesin subunits for biochemical and
structural features; identification of kinesin receptor(s); and characterization of
regulatory mechanisms for both kinesin motility and binding to organelles; and roles
played by kinesin related proteins in neuronal differentiation.
Specialization of the neuronal cytoskeleton is critical to establishment of connections
and maturation of the nervous system. Our studies focus on molecular specializations of
the axonal cytoskeleton, including unique posttranslational modifications of tubulin. Such
specializations affect axonal plasticity and neuronal morphologies. Quantitative and
qualitative changes in the axonal cytoskeleton are being evaluated with a goal of
understanding molecular mechanisms in neuronal cytoskeletal function and neuropathology.
Communication between glia and axon is more complex than previously recognized,
suggesting that glia play major roles in sculpting the functional architecture of neurons.
We previously showed that myelination affects slow axonal transport, regeneration and
neurofilament organization. Microenvironmental cues from glia and target cells may also
target proteins to specific domains of a neuron, including delivery of synaptic vesicles
to terminals and sodium channels to nodes of Ranvier. Glial modulation of neuronal
function is being evaluated. Comparing the effects of CNS and PNS myelination on neurons
shows how different glial environments affect the nervous system. Mutant and transgenic
mouse models are being used to define interactions between glia and neurons and to
identify signal transduction pathways for modulation of neuronal function by myelinating
glia.
Finally, neurological problems have been associated with extended exposure to the
conditions of space flight, which include persistent changes in motor, hypothalamic and
sensory function. Such changes may involve both functional and morphological alterations
in the brain, but underlying mechanisms are unclear. Physiological stress is commonly
associated with a wide range of human activities, but much less attention has been paid to
the effects of modest chronic stress than of acute stress. Stress may alter homeostatic
mechanisms for maintaining neuronal function and many stress-related effects resemble
changes in the aging nervous system. These studies analyze the effects of space flight and
elevated corticosteroids on the dynamics, organization, and composition of the neuronal
cytoskeleton and vesicle trafficking in a mouse model.
Selected Publications:
S.T. Brady, L.L. Kirkpatrick, A. Witt, C. Readhead, B. Tu and V.M.-Y. Lee (1999)
Formation Of Compact Myelin Is Required For Maturation of the Axonal Cytoskeleton. J.
Neuroscience (in press)
J.D. Huang, S.T. Brady, B.W. Richards, D. Stenoien, J.H. Resau, N.G. Copeland, and N.A.
Jenkins (1999) Direct Interaction of Microtubule- and Actin-based Transport Motors. Nature
397:267-270
N. Ratner, G.S. Bloom, and S.T. Brady (1998) A Role for Cdk5 Kinase in Fast Anterograde
Axonal Transport: Novel Effects of Olomoucine and the APC Tumor Suppressor Protein. J.
Neurosci. 18:7717-7726.
Sack, S., J. Muller, A. Marx, M. Thormahlen, E. M. Mandelkow, S. T. Brady, and E.
Mandelkow. 1997. X-ray structure of motor and neck domains from rat brain kinesin.
Biochemistry 36:16155-16165.
Stenoien DS and Brady ST (1997) Immunochemical analysis of kinesin light chain
function. Molec Biol Cell 8:675-689
Brady ST (1995) Biochemical and Functional Diversity of Microtubule Motors in the
Nervous System. Curr. Opinion Neurobiol 5:551-558
Brady ST (1992) Axonal dynamics and regeneration in Neuroregeneration (ed. A. Gorio) Raven
Press, NY pp 7-36
Page maintained by Stephanie
Robertson
Last updatd: 17 Nov 2000
Extraction Method: Expand using Medical Synonyms-
Eliminated words list: MedlinePlus List
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Similarity Method: Weighted keyword count
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Database: Medline abstracts (1967 - Present)
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Publication Type: All
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Score Calculation Method: Cosine Similarity Method
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Results computed on: 6/9/2006