Research Interest
We use an array of proteomic, biochemical and cell biology techniques to study neurodegenerative diseases, particularly amyotrophic lateral sclerosis (ALS, Lou Gehrig’s disease). We are interested in understanding protein degradation and aggregation, oxidative stress, mitochondrial dysfunction and axonal transport in ALS and other neurodegenerative diseases.
Developing innovative proteomic methodologies to enable quantitative analysis of proteins and protein modifications is another interest of the laboratory. Moreover, we have been collaborating to apply proteomic approaches to multiple biomedical fields, including prostate cancer, diabetes and environmental toxicology.
Representative Publications
Ström, A., Shi, P., Zhang, F., Gal, J., Kilty, R., Hayward, L. J. and Zhu, H. “Interaction with functional dynein-mediated retrograde transport system facilitates formation of large aggregates / inclusions of familial ALS SOD1 mutants”, (2008) Journal of Biological Chemistry, in press.
Ström, A., Gal, J., Shi, P., Kasarskis, E., J., Hayward, L. J. and Zhu, H. “Retrograde axonal transport and motor neuron disease” (2008) Journal of Neurochemistry, 106, 495-505.
Babu, J. R., Seibenhener, M. R., Peng, J., Ström, A., Kemppainen, R., Cox, N., Zhu, H., Wooten, M. C., Diaz-Meco, M. T., Moscat, J. and Wooten. M.W. “Genetic inactivation of p62 leads to accumulation of hyperphosphorylated Tau and neurodegeneration”, (2008) Journal of Neurochemistry, 106, 107-20.
Gal, J., Ström, A., Kilty, R., Zhang, F. and Zhu, H. “p62/Sequestosome 1 is upregulated and enhances aggregate formation in model systems of familiar amyotrophic lateral sclerosis” (2007) Journal of Biological Chemistry, 282, 11068-11077.
Zhang, F., Strom, A., Fukada, K., Lee, S., Hayward, L. J. and Zhu, H. “Interactions between familial ALS-linked SOD1 mutants and dynein complex”, (2007) Journal of Biological Chemistry, 282, 16691-16699.
Potter, S. Z., Zhu, H., Shaw,, B. F., Rodriguez, J. A., Doucette, P. A., Sohn, S. H., Durazo, A., Faull, K. F., Gralla, E. B., Nersissian, A. M. and Valentine, J. S. “Binding of a single zinc ion to the copper-zinc superoxide dismutase apoprotein profoundly affects the structure and stability of the entire homodimeric protein” (2007) Journal of American Chemical Society, 129, 4575 -4583.
Hou, X., Liu, R., Ross, S. A., Smart. E. J. Zhu, H. * and Gong, W.* “Crystallographic studies of human MitoNEET”, (2007) Journal of Biological Chemistry, 282, 33242-33246. (*: co-corresponding author)
Tang, X., Gal, J., Zhuang, X., Wang, W., Zhu, H.* and Tang, G.* “A simple array platform for microRNA analysis and its application in mouse tissues”, (2007) RNA, 13, 1803-22. (*: co-corresponding author)
Zhang, F and Zhu, H. “Intracellular conformational alterations of mutant SOD1 and its implications for fALS-associated SOD1 mutant induced motor neuron cell death”, (2006) Biochimica et Biophysica Acta, 1760, 404-14.
Zhu, B., Fukada, K, Zhu, H and Kyprianou, N, “Prohibitin and cofilin are intracellular effectors of transforming growth factor b signaling in human prostate cancer cells”, (2006) Cancer Research, 66, 8640-8647.
Lu, X. and Zhu, H. “Tube-Gel digestion: A novel proteomic approach for high throughput analysis of membrane proteins” (2005) Molecular and Cellular Proteomics, 4, 1948-1958.
Fukada, K., Zhang, F., Vien, A., Cashman, N. R. and Zhu, H. “Mitochondrial proteomic analysis of motor neuron-like cells expressing superoxide dismutase 1 mutants linked with familial amyotrophic lateral sclerosis”, (2004) Molecular and Cellular Proteomics, 3, 1211-1223.
Zhu, H., Hunter, T. C., Pan, S., Bradbury, E. M., Chen, X. “Residue-specific mass signatures for the efficient identification of protein modifications by mass spectrometry”, (2002) Analytical Chemistry, 74, 1687-1694.
Zhu, H., Pan, S., Gu, S., Bradbury, E. M. and Chen, X. “Amino Acid Residue-Specific Stable Isotope Labeling for Quantitative Proteomics”, (2002) Rapid Communications in Mass Spectrometry, 16, 2115-2123.
Zhu, H., Shipp, E., Sanchez, R. J., Liba, A., Stein, J., Hart, J. P., Gralla, E. B., Nersissian, A. M. and Valentine, J. S. “Cobalt(2+) binding to human and tomato copper chaperone for superoxide dismutase: implications for the metal ion transfer mechanism” (2000) Biochemistry, 39, 5413-5421.
Goto, J. J., Zhu, H., Sanchez, R. J., Nersissian, A. M., Gralla, E. B., Valentine, J. S. and Cabelli, D. E. “Loss of in vitro metal ion binding specificity in mutant copper-zinc superoxide dismutases associated with familial amyotrophic lateral sclerosis” (2000) J. Biol. Chem., 275, 1007-1014.
Hall, L. T., Sanchez, R. J., Holloway, S. P., Zhu, H., Stine, J. E., Lyons, T. J., Demeler, B., Schirf, V., Hansen, J. C., Nersissian, A. M., Valentine, J. S., and Hart, P. J. “X-ray crystallographic and analytical ultracentrifugation analyses of truncated and full-length yeast copper chaperone for SOD (LYS7): a dimer-dimer model of Lys7-SOD association and copper delivery”, (2000) Biochemistry, 39, 3611-3623.
Liu, H., Zhu, H., Nersissian, A. M., Eggers, D. K., Faull, K. F., Goto, J. J., Ai, J., Sanders-Loehr, J., Gralla, E. B. and Valentine, J. S. “Copper(2+) binding to the surface residue Cys111 of His46Arg human copper-zinc superoxide dismutase, a familial amyotrophic lateral sclerosis mutant”, (2000) Biochemistry, 39, 8125-8132.
Cabelli, D. E., Riley, D., Rodriguez, J., Valentine, J. S., Zhu, H. “Models of superoxide dismutase” in Biomimetic Oxidations Catalyzed by Transition Metal Complexes Meunier, B. ed., (2000) Imperial College Press, London, 461-508.
Postdoctoral fellows and graduate students positions are available, contact me for the opportunities!
Experience in one of the following fields is required: molecular biology, neurobiology, yeast genetics, protein chemistry, and biological mass spectrometry.
Group Pictures
