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James H. Eberwine, Ph.D.
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Elmer Holmes Bobst Professor of Pharmacology
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Department: Systems Pharmacology and Translational Therapeutics
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Graduate Group Affiliations
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Contact information
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Department of Pharmacology
1f 38 John Morgan Building
3a 3620 Hamilton Walk
Philadelphia, PA 19104-6084
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1f 38 John Morgan Building
3a 3620 Hamilton Walk
Philadelphia, PA 19104-6084
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Office: (215) 898-0420
34 Fax: (215) 573-7188
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34 Fax: (215) 573-7188
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Email:
eberwine@upenn.edu
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eberwine@upenn.edu
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Publications
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Education:
21 9 B.S. 19 (Biochemistry) c
28 Yale University, 1978.
21 9 M.A. 19 (Biochemistry) c
2c Columbia University, 1979.
21 a Ph.D. 19 (Biochemistry) c
2c Columbia University, 1984.
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21 9 B.S. 19 (Biochemistry) c
28 Yale University, 1978.
21 9 M.A. 19 (Biochemistry) c
2c Columbia University, 1979.
21 a Ph.D. 19 (Biochemistry) c
2c Columbia University, 1984.
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Links
9a Search PubMed for articles
7d Primary Work Website
43 Pharmacological Sciences graduate group faculty webpage.
41 Faculty Profile, Graduate Group in Neuroscience, University of Pennsylvania School of Medicine
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Permanent link9a Search PubMed for articles
7d Primary Work Website
43 Pharmacological Sciences graduate group faculty webpage.
41 Faculty Profile, Graduate Group in Neuroscience, University of Pennsylvania School of Medicine
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c2 Molecular basis of neuronal adaptation with emphasis on the following adaptive processes; tetanic potentiation, glucocorticoid-induced, age-induced as well as opiate-induced adaptation.
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1b RESEARCH TECHNIQUES
96 Molecular biology; single-cell genetics; cDNA cloning; in situ hybridization; in situ transcription; mRNA amplification; expression profiling
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18 RESEARCH SUMMARY
714 The research efforts of my laboratory are directed towards understanding the molecular basis of neuronal functioning. Our experimental approach is reductionist in nature and involves analysis of gene expression in individual cells dispersed in culture, in the live slice preparation or from fixed pathological tissue specimens. We have developed various procedures that have enabled the analysis of cellular functioning using single cells as the experimental model. These procedures include those that permit an analysis of the mRNA complement, the protein complement and an assessment of mRNA movement and translation within single cells. This level of analysis is important since an individual cells biochemical compostion may be diluted by that of surrounding cells. We are currently generating molecular and bioprocess fingerprints of various cell types and disease states. When this is complete, we hope that it will be possible to alter the cellular response to various challenges by altering the levels of these biological processes in a predictable manner. As part of these studies, we are examining the role of subcellular localization of mRNAs in regulating cellular function. We have shown that multiple mRNAs are localized in neuronal dendrites and have provided a formal proof of local mRNA translation in dendrites. Further, we have recently shown that the intracellular sites of localization and translation of these mRNAs can be altered by synaptic stimulation highlighting for the first time that in vivo translation of a mRNA can occur at different rates in distinct regions of a single cell (translation is primarily exponential in dendrites and linear in the cell soma). These insights into the cell biology of neuronal function highlight the complexities that remain to be understood.
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Description of Research Expertise
23 RESEARCH INTERESTSc2 Molecular basis of neuronal adaptation with emphasis on the following adaptive processes; tetanic potentiation, glucocorticoid-induced, age-induced as well as opiate-induced adaptation.
8
8
1b RESEARCH TECHNIQUES
96 Molecular biology; single-cell genetics; cDNA cloning; in situ hybridization; in situ transcription; mRNA amplification; expression profiling
8
18 RESEARCH SUMMARY
714 The research efforts of my laboratory are directed towards understanding the molecular basis of neuronal functioning. Our experimental approach is reductionist in nature and involves analysis of gene expression in individual cells dispersed in culture, in the live slice preparation or from fixed pathological tissue specimens. We have developed various procedures that have enabled the analysis of cellular functioning using single cells as the experimental model. These procedures include those that permit an analysis of the mRNA complement, the protein complement and an assessment of mRNA movement and translation within single cells. This level of analysis is important since an individual cells biochemical compostion may be diluted by that of surrounding cells. We are currently generating molecular and bioprocess fingerprints of various cell types and disease states. When this is complete, we hope that it will be possible to alter the cellular response to various challenges by altering the levels of these biological processes in a predictable manner. As part of these studies, we are examining the role of subcellular localization of mRNAs in regulating cellular function. We have shown that multiple mRNAs are localized in neuronal dendrites and have provided a formal proof of local mRNA translation in dendrites. Further, we have recently shown that the intracellular sites of localization and translation of these mRNAs can be altered by synaptic stimulation highlighting for the first time that in vivo translation of a mRNA can occur at different rates in distinct regions of a single cell (translation is primarily exponential in dendrites and linear in the cell soma). These insights into the cell biology of neuronal function highlight the complexities that remain to be understood.
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cf Wu C-K, Zeng, F, Eberwine, J: mRNA transport to and translation in neuronal dendrites [Review] Anal Bioanal Chem 387: 59-62, Jan 2007.
131 Barrett LE, Sul JY, Takano H, Van Bockstaele EJ, Haydon PG, Eberwine JH: Region-directed phototransfection reveals the functional significance of a dendritically synthesized transcription factor. Nature Methods 3: 455-460, Jun 2006.
116 Barrett LE, Van Bockstaele EJ, Sul JY, Takano H, Haydon PG, Eberwine JH: Elk-1 associates with the mitochondrial permeability transition pore complex in neurons. Natl Acad Sci USA 103: 5155-5160, Mar 2006.
129 Zielinski J, Kilk K, Peritz T, Kannanayakal T, Miyashiro KY, Eiriksdottir E, Jochems J, Langel U, Eberwine J: In vivo identification of ribonucleoprotein-RNA interactions. Proc National Acad Sci USA 103: 1557-1562, Jan 2006.
eb Peritz T, Zeng F, Kannanayakal TJ, Kilk K, Eiriksdottir E, Langel U, Eberwine J: Immunoprecipitation of mRNA-protein complexes. Nature Protocols 1: 577-580, 2006.
114 Zeng F, Peritz T, Kannanayakal TJ, Kilk K, Eiriksdottir E, Langel U, Eberwine J: A protocol for PAIR: PNA-assisted identification of RNA binding proteins in living cells. Nature Protocols 1: 920-7, 2006.
fa Glanzer J, Miyashiro KY, Sul J-Y, Barrett L, Belt B, Haydon P, Eberwine J: RNA splicing capability of live neuronal dendrites. Proc Natl Acad Sci USA 102: 16859-16864, Nov 2005.
c9 Miyashiro K and Eberwine J: Fragile X syndrome: (What's) lost in translation? Proc Natl Acad Sci USA 101: 17329-17330, Dec 2004.
160 Marciano PG, Brettschneider J, Manduchi E, Davis JE, Eastman S, Raghupathi R, Saatman KE, Speed TP, Stoeckert CJ Jr, Eberwine JH, McIntosh TK: Neuron-specific mRNA complexity responses during hippocampal apoptosis after traumatic brain injury. J Neurosci 24: 2866-2876, Mar 2004.
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Selected Publications
16b Bell TJ, Miyashiro KY, Sul, J-Y, McCullough R, Buckley PT, Jochems J, Meaney DF, Haydon P, Cantor C, Parsons TD, Eberwine, J: Cytoplasmic BK(Ca) channel intron-containing mRNAs contribute to the intrinsic excitability of hippocampal neurons. Proc Natl Acad Sci USA 105: 1901-1906, Feb 2008.cf Wu C-K, Zeng, F, Eberwine, J: mRNA transport to and translation in neuronal dendrites [Review] Anal Bioanal Chem 387: 59-62, Jan 2007.
131 Barrett LE, Sul JY, Takano H, Van Bockstaele EJ, Haydon PG, Eberwine JH: Region-directed phototransfection reveals the functional significance of a dendritically synthesized transcription factor. Nature Methods 3: 455-460, Jun 2006.
116 Barrett LE, Van Bockstaele EJ, Sul JY, Takano H, Haydon PG, Eberwine JH: Elk-1 associates with the mitochondrial permeability transition pore complex in neurons. Natl Acad Sci USA 103: 5155-5160, Mar 2006.
129 Zielinski J, Kilk K, Peritz T, Kannanayakal T, Miyashiro KY, Eiriksdottir E, Jochems J, Langel U, Eberwine J: In vivo identification of ribonucleoprotein-RNA interactions. Proc National Acad Sci USA 103: 1557-1562, Jan 2006.
eb Peritz T, Zeng F, Kannanayakal TJ, Kilk K, Eiriksdottir E, Langel U, Eberwine J: Immunoprecipitation of mRNA-protein complexes. Nature Protocols 1: 577-580, 2006.
114 Zeng F, Peritz T, Kannanayakal TJ, Kilk K, Eiriksdottir E, Langel U, Eberwine J: A protocol for PAIR: PNA-assisted identification of RNA binding proteins in living cells. Nature Protocols 1: 920-7, 2006.
fa Glanzer J, Miyashiro KY, Sul J-Y, Barrett L, Belt B, Haydon P, Eberwine J: RNA splicing capability of live neuronal dendrites. Proc Natl Acad Sci USA 102: 16859-16864, Nov 2005.
c9 Miyashiro K and Eberwine J: Fragile X syndrome: (What's) lost in translation? Proc Natl Acad Sci USA 101: 17329-17330, Dec 2004.
160 Marciano PG, Brettschneider J, Manduchi E, Davis JE, Eastman S, Raghupathi R, Saatman KE, Speed TP, Stoeckert CJ Jr, Eberwine JH, McIntosh TK: Neuron-specific mRNA complexity responses during hippocampal apoptosis after traumatic brain injury. J Neurosci 24: 2866-2876, Mar 2004.
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