Associate Professor of Neurosurgery
Neurological Surgery; Neurology
I have two major research interests: trophic factors as novel treatments for Parkinson‘s disease and CNS neoplasms. My lab has been characterizing the response to trauma in the caudate nucleus of parkinsonian animals. This work grew out of the observation that tissue grafts for parkinsonism lead to modest behavioral improvement, even when the graft did not survive. We have shown that several trophic factors are present in the caudate of rats after trauma which simulates graft placement. Both brain derived neurotrophic factor and ciliary neurotrophic factor are found in the caudate predictably at intervals after the surgical trauma. Further, there is at least one other, as yet unidentified factor present after trauma in the caudate. We have moved beyond identification to use of BDNF in parkinsonian models. Infusion of BDNF into the dopamine deficient caudate of a hemiparkinsonian rat leads to behavioral improvement and increased tyrosine hydroxylase (TH) staining, the rate limiting enzyme for dopamine synthesis. We are currently working on a delivery system to distribute BDNF, or other macromolecules like trophic factors, in the striatum of primates.
The second area of active interest is in two forms of CNS neoplasia: leukemic meningitis and glioblastoma multiforme (GBM). We have created an animal model of leukemic meningitis in the athynic (nude) rat, using a human leukemic cell line. In collaboration with Dr. Steve Greenberg, we are working on a gene therapy approach using a white cell specific promoter and the viral thymidine kinase "suicide" enzyme. We are testing the constructs in vitro and in the nude rat model. In addition, we are working withDr. Greenberg to study the biology of GBM by transfecting human GBM cell lines with genes for vascular growth factors. Basic fibroblast growth factor, transforming growth factor beta, and endothelin-1 are currently being studied. The behavior of the transfected GBM cell lines are characterized in vitro, and after implantation into the frontal lobe of nude rats. By understanding how the transfected genes affect tumor growth, we hope to devise novel treatment strategies, potentially utilizing gene therapy.