We have a longstanding interest in the use of stem cells as disease models and as therapeutics for neurodegenerative disorders such as Parkinson's and Alzheimer's diseases. We are currently undertaking several complementary tacks. First, we are attempting to improve existing approaches for the generation of neurons from patient skin cells. One focus, to this end, is to better understand the reprogramming process by which human skin cells are converted to a pluripotent embryonic stem cell-like state, termed iPS cells. Another focus is to try to simplify the process of making various neuron types from skin cells. Such cells could ultimately serve as ‘replacement’ cells in disease. A second goal is to generate neurons from patients with neurological disorders such as Parkinson's and Alzheimer's, as such cells would inform us about the underlying mechanism of disease. We have generated such models of Alzheimer's and Parkinson's disease, and are characterizing cellular and molecular phenotypes. Future studies may use these cell models for therapeutic screening. We do this work in conjunction with analysis of novel animal models of these disorders.
Kim, J.P., Murchison, E., Hannon, G., and Abeliovich, A.
miRNAs regulation of midbrain dopamine neurons: Mir133b functions in a feedback circuit with the homeodomain transcription factor Pitx3. Science 317:1220-24. (2007)
Martinat, C., Bacci, J.J., Leete, T., Kim, J., Vanti, W.B., Newman, A.H., Cha, J.H., Gether, U., Wang, H. Abeliovich, A.
Cooperative transcription activation by Nurr1 and Pitx3 induces embryonic stem cell maturation to the midbrain dopamine neuron phenotype. Proc Natl Acad Sci U S A 103:2874-79. (2006)
Martinat, C., Shendelman, S., Jonason, A., Leete, T., Beal, M.F., Yang, L., Floss, T. & Abeliovich, A.
Sensitivity to oxidative stress in DJ-1-deficient dopamine neurons: an ES- derived cell model of primary Parkinsonism. PLoS Biol e237:. (2004)