W. MICHAEL ZAWADA, Ph.D.

         My research interests focus on the signaling pathways mediating neuronal survival and death and use of our findings in discovery of more effective treatments for Parkinson's disease and other neurodegenerative conditions. Transplantation of fetal dopamine cells shows promise for repair of the damaged dopaminergic circuitry in parkinsonian patients, however death of most of the transplanted cells is a major hurdle for this experimental cell replacement therapy. Both cultured and transplanted dopamine neurons die by apoptosis, which can be reduced by neurotrophic growth factors and inhibitors of a p38 mitogen-activated protein kinase. These studies involve culturing primary neurons and a variety of biochemical and histochemical assays.

         Within the first 24 hours after transplantation of embryonic dopamine neurons into the brains of parkinsonian rats most neurons die by apoptosis. My laboratory explores the possibility that neurotrophic factors which stimulate antiapoptotic pathways and inhibitors of proapoptotic pathways may rescue transplanted neurons from death. These experiments require neurosurgery, behavioral studies, HPLC, and immunocytochemistry. This work may soon lead to use of growth factors in neurotransplantation in humans.

         A second area of my research is the evaluation of alternative and abundant sources of cells for use in transplantation. We are using somatic cell cloning to generate identical bovine embryos for transplantation. The ability to genetically modify such embryos may allow us to engineer the cells to reduce or prevent host's immune response against a xenograft. Because cloned neurons have identical genetic makeup, they can be effectively screened for latent viruses and may lead to more predictable transplants. These experiments are conducted in collaboration with biotechnology industry and utilize molecular biology and somatic cell cloning techniques.

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Representative Publications

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         Full list of publications (PubMed)