Jian Liu, Ph.D.
Email: LiuJ@cpmcri.org
Introduction
My laboratory is interested in understanding one of the neurodegenerative diseases called Amyotrophic Lateral Sclerosis (ALS, also known as Lou Gherig's disease). One proven cause of ALS is mutations in the copper/zinc superoxide dismutase (SOD1) gene. Animal models are well established for studying disease mechanisms and testing therapeutic drugs in vivo.
Currently, we are focusing on understanding the involvement of mitochondria in disease pathology. Previous studies in both ALS patients and animal models have demonstrated, that different from the wild type, mutated SOD1s are selectively accumulated in mitochondria of disease-affected tissues and resulting in covalent modifications of mitochondria-associated proteins including mutant SOD1s themselves. These features are also independent of the Copper Chaperone for SOD1 (CCS) and dismutase enzymatic activity. Research projects conducted in the laboratory are designed to answer the following questions and potential many others they might lead to in the future: 1) Are mutant SOD1s in spinal cord mitochondria sufficient and necessary to cause disease? 2) What are the cellular and molecular mechanisms of a fraction of SOD1s targeted to the subcellular mitochondrial in addition to cytoplasmic locations? 3) What is the nature of covalent modifications to mitochondria-associated proteins by mutant SOD1s? 4) What are the target proteins that mutant SOD1s interact with? 5) What are the downstream signal pathways of these interactions that eventually lead to motor neuron death in ALS? 6) What potential sites in the mitochondrial pathological pathways one can design/apply drugs towards therapeutic treatment of ALS?
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Publications
Click here for List of publications by J Liu, Ph.D. in PubMed.
Representative publications include:
1. Liu, J., Shinobu, L.A., Ward, C.M., Young, D., Cleveland, D.W. (2005) Elevation of the Hsp70 chaperone does not effect toxicity in mouse models of familial amyotrophic lateral sclerosis. J.Neurochem. 93:875-882.
2. Liu, J., Lillo, C., Jonsson, P.A., Vande Velde, C., Ward, C.M., Miller, T.M., Subramaniam, J.R., Rothstein, J.D., Marklund, S., Andersen, P.M., Brannstrom, T., Gredal, O., Wong, P.C., Williams, D.S., and Cleveland, D.W. (2004) Toxicity of familial ALS-linked SOD1 mutants from selective recruitment to spinal mitochondria. Neuron 43:5-17.
3. Subranmaniam, J.R., Lyons, W.E., Liu, J., Bartnikas, T.B., Rothstein, J., Price, D.L., Cleveland, D.W., Gitlin, J.D., and Wong, P.C. (2002) Mutant SOD1 causes motor neuron disease independent of CCS-mediated copper loading. Nat. Neurosci. 5:301-307.
4. Howland, D.S., Liu, J., She, Y., Goad, B., Margakis, N.J., Kim, B., Erickson, J., Kulik, J., DeVito, L., Psaltis, G., DeGennaro, L.J., Howland, D.S., Cleveland, D.W., and Rothstein, J.D. (2002) Focal loss of the glutamate transporter EAAT2 in a transgenic rat model of mutant SOD1-mediated Amyotrophic Lateral Sclerosis (ALS). Proc. Natl. Acad. Sci. USA 99: 1604-1609.
5. Cleveland, D.W. and Liu, J.(2000) Oxidation versus aggregation-how do SOD1 mutants cause ALS? Nature Med. 6:1320-1321.
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