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H. David Shine, PhD
Education: Trask, T.W., Trask, R.P., Aguilar-Cordova, E., Shine, H.D., Wyde, P.R., Goodman, J.C., Hamilton, W.J., Rojas-Martinez, A., Chen, S-H., Woo, S.L.C., Grossman, R.G. Phase I study of adenoviral delivery of the HSV-tk gene and ganciclovir administration in patients with recurrent malignant brain tumors. Mol. Med. 1:195-203, 2000. Castro, R.F, Jackson, J.A., Goodell, M.A. Robertson, C.S. Liu, H. and Shine, H.D. Failure of bone marrow cells to transdifferentiate into neural cells in vivo. Science 297: 1299, 2002 Zou L, Yuan X, Long Y, Shine HD, and Yang K Improvement of spatial learning and memory after adenovirus-mediated transfer of the nerve growth factor gene to aged rat brain. Hum Gene Ther 13:2173-2184, 2002. Zhou, L, Baumgartner, BJ, Hill-Felberg, SJ, McGowen, LR and Shine, HD Neurotrophin-3 expressed in situ induces axonal plasticity in the adult injured spinal cord. J. Neurosci. 23:1424-1431, 2003. Zhou, L and Shine, HD Neurotrophic factors expressed in the cortex and spinal cord induce axonal plasticity in the injured spinal cord. J Neurosci Res 74:221-226, 2003. Olmsted-Davis EA, Gugala Z, Camargo F, Gannon FH, Jackson K, Kienstra KA, Shine HD, Lindsey RW, Hirschi KK, Goodell MA, Brenner MK, and Davis AR. Adult hematopoietic stem cells can function as osteoblast precursors. Proc Natl Acad Sci U S A 23:15877-82, 2003. Wu YJ, Kruttgen A, Moller JC, Shine D, Chan JR, Shooter EM, Cosgaya JM Nerve growth factor, brain-derived neurotrophic factor, and neurotrophin-3 are sorted to dense-core vesicles and released via the regulated pathway in primary rat cortical neurons. J Neurosci Res 75:825-34, 2004. Grider MH, Mamounas LA, Le W, Shine HD In situ expression of brain-derived neurotrophic factor or neurotrophin-3 promotes sprouting of cortical serotonergic axons following a neurotoxic lesion. J. Neurosci Res 82:404-12, 2005. 
Departments of Neurosurgery,
Molecular & Cellular Biology,
Neuroscience,
Baylor College of Medicine
Contact Information:
hshine@bcm.edu
713-798-3828
B.A. Texas Tech University
M.A. University of Texas, Austin
Ph.D., The University of Texas Medical Branch
Postdoctoral Fellow, Harvard Medical School
Research Interests:
The research interests of our laboratory focus on the molecular
and cellular bases of disease and trauma of the nervous system. Projects
include the study of the role of neurotrophic factors in CNS degeneration
and regeneration as a consequence of trauma or neurodegenerative disease
and the role immuno-modulatory cytokines in CNS tumors and their possible
therapeutic use.
Several neurotrophic factors have neuroprotective activity that can
ameliorate the consequences of insults to the CNS such as stroke, trauma,
or neurodegenerative processes. We cloned genes for several neurotrophic
factors into a replication·defective adenoviral vector that is
relatively easily produced, infects a wide variety of cells including
neurons and glia, is capable of directing a high degree of recombinant
protein expression. We have shown that these vectors are taken up by
nerves and transported back to the CNS where the recombinant genes are
expressed. Vectors carrying genes for BDNF, CNTF, and GDNF spare neurons
from axotomy-induced neuronal death. The vector carrying GDNF will ameliorate
dopaminergic neuronal death in a model of Parkinson's disease. We are
now investigating the effect of adenoviral·mediated expression
of neurotrophic factors in spinal cord injury and in a mutant mouse
model of motoneuron degeneration.
In another area of research we demonstrated that adenoviral-mediated
transduction of brain tumors may be an effective treatment. We have
tested this treatment in a phase I clinical trial. We are now testing
whether delivery of vectors carrying immuno-modularly genes such as
cytokines will amplify the tumoricidal effects.
Selected Publications:
Baumgartner, B.J. and Shine, H.D. Neuroprotection of CNS neuron by retrograde transport of adenoviral vectors carrying neurotrophic genes. J Neurosci. 17:6504-6511, 1997.
©2002,
Cell And Gene Therapy, Baylor College
of Medicine
One Baylor Plaza, N1002, Houston, TX 77030, (713)798-1246
URL: http://www.bcm.edu/genetherapy
Email:cagt@bcm.edu
(Modified:August 15, 2006- SM)
