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Research Interests
Following injury, nerves of the central nervous
system (CNS) do not spontaneously regenerate their axons. Lesioned
ends of the injured axons encounter an environment that is inherently
inhibitory to regrowth, containing myelin-associated inhibitors
and a growth-inhibitory astrocytic glial scar. The lack of repair
and regrowth can lead to significant functional deficits after
nerve damage. To change the balance of CNS molecules to favor
regeneration, we must understand the net response of neurons to
the multiple, varied molecular cues present after injury.
The overall goal of my research program is
to elucidate the cellular and molecular mechanisms that underlie
nerve regeneration, through the synthesis and analysis of in vitro
systems that closely approximate the in vivo CNS tissue organization.
My group utilizes laser techniques to create nervous tissue analogs
with a high degree of control over cell position and molecular
function. Laser-guided direct writing employs optical forces to
guide the deposition of cells in solution onto a substrate, with
micron-scale resolution. Chromophore-assisted laser inactivation
transiently eliminates the function of a single protein through
binding it to an antibody that is conjugated to a chromophore.
Subsequent excitation of the chromophore with laser light results
in specific protein inactivation. We are working to establish
conditions in which a neuron can grow over or past an inhibitory
molecule, with the aid of a permissive molecule. Mathematical
models are being developed to correlate neurite extension with
the relative abilities of particular molecules, individually and
in combination, to promote growth.
The long-term objective of this research is
to achieve nerve regeneration following CNS nerve injury. Successful
nerve regeneration requires that a balance in favor of growth
be established between permissive and inhibitory cues. Our experiments
take steps to elucidate the relative contributions of multiple
molecular signals that influence growth after nerve injury. This
work has the potential to influence the development of clinical
interventions, from pharmacological therapies to tissue engineered
nerve substitutes.
Dorsal root ganglion neuron cultured on
a laminin substrate in the presence of nerve growth factor.
The extending axon ends in a growth cone, a structure
that is highly specialized for sensing the surrounding
environment.
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Courses Taught
Bio 112 – Biomaterials (beginning Spring
2003)
Selected Publications
Hong, T.; Maish, M. S.; Cohen, J.; Fitzpatrick,
P.; Bert, A. A.; Harper, J. S.; Feng, D.; Hoffman-Kim, D.; Hopkins,
R. A.
"Reproducible Echocardiography in Juvenile Sheep and Its
Application in the Evaluation of A Pulmonary Valve Homograft Implant"
Contemporary Topics in Lab Animal Science 2000, 39, 15.
Hoffman-Kim, D.; Lander, A. D.; Jhaveri, S.
"Regional differences in immunostaining for chondroitin sulfate
in the developing tectum reflect differential GAG biosynthesis"
Journal of Neuroscience 1998, 18, 5881.
Hoffman, D.; Breakefield, X. O.; Short, M.
P.; Aebischer, P.
"Transplantation of a polymer encapsulated cell line genetically
engineered to release NGF" Experimental Neurology 1993,
122, 100.
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