H. David Shine, Ph.D.
Department of Neurosurgery
Department of Molecular and Cellular Biology
Department of Neuroscience
- B.A., Texas Tech University
- M.A., University of Texas, Austin
- Ph.D., The University of Texas Medical Branch
- Postdoctoral Fellow, Harvard Medical School
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.
- Goodman JC, Trask TW, Chen S·H, Woo SLC, Grossman RG, Carey KD, Hubbard G, Carrier DA, Rajagopalan S, Aguilar-Cordova E, and Shine HD. 1996. Adenoviral-mediated thymidine kinase gene transfer into the primate brain followed by systemic ganciclovir: pathologic, radiologic and molecular studies. Hum. Gene Ther. 7:1241·1250.
- Baumgartner BJ and Shine HD. 1997. Neuroprotection of CNS neuron by retrograde transport of adenoviral vectors carrying neurotrophic genes. J Neurosci. 17:6504·6511.
- Baumgartner BJ and Shine HD. 1998. Neuroprotection of spinal motoneurons following targeted transduction with an adenoviral vector carrying the gene for glial cell-line derived neurotrophic factor. Exp. Neurol. 153:102·112.
- Baumgartner BJ and Shine HD. 1998. Permanent rescue of lesioned motoneurons and enhanced axonal regeneration by adenovirus mediated expression of glial cell·line derived neurotrophic factor. J. Neurosci. Res. 54:766·777.
- Trask TW, Trask RP, Aguilar-Cordova E, Shine HD, Wyde PR, Goodman JC, Hamilton WJ, Rojas-Martinez A, Chen S-H, Woo SLC, Grossman RG. 2000. 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.
- 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
- Castro RF, Jackson KA, Goodell MA, Robertson CS, Liu H and Shine, HD. Response t Is absence of proof proof of absence? Science 299: 1184, 2003.
- 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.