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Functional genomics in central nervous system injurySpinal cord injury begins with a traumatic contusion which destroys cells. but continues with the inflammation of surviving tissues leading to secondary cell death. We used functional genomics to characterize the cellular changes occurring during this critical period in hopes of intervening to rescue function. Recent work focuses on gene expression in selected regenerating brain neurons after spinal cord injury. We label individual neurons with retrograde dyes and then use laser capture microscopy to recover injured cells with axons extending distal to the injury site. Following amplification and microarray assays. individual mRNAs selective for regenerating neurons can be identified. We also study the role of T cells in exacerbation of spinal cord injury. Other new projects focus on micro RNAs in stem cells and regenerating neurons. Many of these projects are ongoing collaborations with spinal cord research groups from throughout the world. One component of my group also designs databases for systematic mining of all microarray and animal data. Our long-term goal is to accelerate the pace of spinal cord injury research through worldwide collaboration. Selected PublicationsLi, H., Chang, Y.W., Mohan, K., Su, H.W., Ricupero, C.L., Baridi, A., Hart, R.P. and Grumet, M. (2008) Activated Notch1 maintains the phenotype of radial glial cells and promotes their adhesion to laminin by upregulating nidogen. Glia 56: 646-658. Lakshmipathy, U. and Hart, R.P. (2008) Concise Review: MicroRNA expression in multipotent Mesenchymal Stromal cells. Stem Cells 26: 356-363. Lakshmipathy, U., Love, B., Goff, L.A., Jörnsten,R., Graichen, R., Hart, R.P. and Chesnut, J.D. (2007) MicroRNA expression pattern of undifferentiated and differentiated human embryonic stem cells. Stem Cells Dev 16: 1003-1016. Goff, L.A., Davila,J., Jörnsten, R., Keles, S. and Hart, R.P. (2007) Bioinformatic analysis of neural stem cell differentiation. J Biomol Tech 18: 205-12. Kigerl, K.A., Lai, W., Rivest, S., Hart, R.P., Satoskar, A.R. and Popovich, A.R. (2007) Toll-like receptor (TLR)-2 and TLR-4 regulate inflammation, gliosis, and myelin sparing after spinal cord injury. J Neurochem. 102: 37-50. Cao, Z., Gao, Y., Bryson, J.B., Hou,J., Chaudhry, N., Siddiq, M., Martinez, J., Spencer, T., Carmel, J., Hart, R.P. and Filbin, M.T. (2006) The cytokine interleukin-6 is sufficient but not necessary to mimic the peripheral conditioning lesion effect on axonal growth. J Neurosci 26: 5565-73. Porter, J.F., Sharma, S., Wilson, D.L., Kappil, M.A., Hart, R.P. and Denhardt, D.T. (2005) Tissue inhibitor of metalloproteinases-1 stimulates gene expression in MDA-MB-435 human breast cancer cells by means of its ability to inhibit metalloproteinases. Breast Cancer Res Treat 94: 185-93. Jones, T.B., Hart, R.P. and Popovich, P.G. (2005) Molecular control of physiological and pathological T-cell recruitment after mouse spinal cord injury. J Neurosci 25: 6576-83. Shaked, I., Tchoresh, D., Gersner, R., Meiri, G., Mordechai, S., Xiao, X., Hart, R.P. and Schwartz, M. (2005) Protective autoimmunity: interferon-gamma enables microglia to remove glutamate without evoking inflammatory mediators. J Neurochem 92: 997-1009. Sullivan, P.G., Rabchevsky, A.G., Keller, J.N., Lovell, M., Sodhi, A., Hart, R.P. and Scheff, S.W. (2004) Intrinsic differences in brain and spinal cord mitochondria: Implication for therapeutic interventions. J Comp Neurol 474: 524-34. Hu, R., Hebbar, V., Kim, B.R., Chen, C., Winnik, B., Buckley, B., Soteropoulos, P. Tolias, P., Hart, R.P. and Kong, A.N. (2004) In vivo pharmacokinetics and regulation of gene expression profiles by isothiocyanate sulforaphane in the rat. J Pharmacol Exp Ther Pan, J.Z., Jörnsten, R. and Hart, R.P. (2004) Screening anti-inflammatory compounds in injured spinal cord with microarrays: a comparison of bioinformatics analysis approaches. Physiol Genomics 17: 201-14. |
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