John H. Carson, Ph.D.
Professor of Molecular, Microbial and Structural BiologyDirector, Graduate Program in Cell Analysis and Modeling
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Academic Office Location: Molecular, Microbial and Structural Biology University of Connecticut Health Center 263 Farmington Avenue Farmington, CT 06030-6406 |
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| Phone: | 860-679-2130 |
| Fax: | 860-679-1039 |
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Carson Lab Page Cell Analysis and Modeling Graduate Program Molecular Biology & Biochemistry Graduate Program Neuroscience Graduate Program |
This laboratory is investigating intracellular trafficking of mRNA in cells of the nervous system using a combination of molecular biological, microinjection, confocal microscopy and three dimensional visualization techniques. We have delineated an RNA trafficking pathway consisting of export from the nucleus, granule assembly in the perikaryon, transport of RNA granules in the processes, localization to the distal regions of the cell and translational activation. We are analyzing the cis/trans regulation of each step in this pathway and have identified a common 21 nucleotide RNA trafficking signal (RTS) in many different transported mRNAs that binds specifically to hnRNPA2 and is involved at various steps in the trafficking pathway. The laboratory is also investigating expression and intracellular trafficking of the gap junction protein, connexin 32, in oligodendrocytes using green fluorescent protein fusions, time lapse confocal imaging, and three dimensional visualization. The laboratory is also involved in developing a comprehensive computational simulation of cellular physiology and behavior. This project, termed the Virtual Cell, consists of a multidisciplinary team of cell biologists, molecular biologists, mathematicians, physicists, computer scientists, engineers and programmers. One goal of the project is to model the intracellular RNA trafficking pathway we have outlined.
Accepting Lab Rotation Students for Summer '13, Fall '13, Spring '14
The Carson lab is studying RNA trafficking in neural cells using single molecule imaging, systems analysis and computational modeling in the Virtual Cell. Rotation students in this lab have the opportunity to learn cell culture, protein chemistry, microinjection, confocal microscopy, fluorescence correlation spectroscopy and computational cell biology. Possible rotation projects in this lab:
1) characterizing dynamic molecular assemblies involved in RNA trafficking using photo-induced biotin transfer from hnRNP A2 to other molecular partners
2) defining conditional operators (EITHER OR, BOTH AND, ONLY IF) controlling molecular interactions in RNA trafficking using cross correlation FCS.
Journal Articles
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Single-molecule imaging of translational output from individual RNA granules in neurons
(2012) Mol Biol Cell 5 (23) 918-29
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Herpes simplex virus type 1 helicase-primase: DNA binding and consequent protein oligomerization and primase activation
(2011) J Virol 2 (85) 968-78
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Differential subcellular distributions and trafficking functions of hnRNP A2/B1 spliceoforms
(2010) Traffic 7 (11) 886-898
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Signaling from the secretory granule to the nucleus: Uhmk1 and PAM
(2010) Molecular Endocrinology 8 (24) 1543-1558
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Model-based global analysis of heterogeneous experimental data using gfit.
(2009) Methods in molecular biology (Clifton, N.J.) (500) 335-359
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Novel DNA binding properties of the Mcm10 protein from saccharomyces cerevisiae
(2009) Journal of Biological Chemistry 37 (284) 25412-25420
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Multiplexed dendritic targeting of α calcium calmodulin-dependent protein kinase II, neurogranin, and activity-regulated cytoskeleton-associated protein RNAs by the A2 pathway
(2008) Molecular Biology of the Cell 5 (19) 2311-2327
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Significant Proportions of Nuclear Transport Proteins with Reduced Intracellular Mobilities Resolved by Fluorescence Correlation Spectroscopy
(2007) Journal of Molecular Biology 1 (365) 50-65
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A Comparison of Conventional Pain Coping Skills Training and Pain Coping Skills Training With a Maintenance Training Component: A Daily Diary Analysis of Short- and Long-Term Treatment Effects
(2006) Journal of Pain 9 (7) 615-625
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A role for Sec8 in oligodendrocyte morphological differentiation
(2006) Journal of Cell Science 5 (119) 807-818
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Heterogeneous nuclear ribonucleoprotein (hnRNP) E1 binds to hnRNP A2 and inhibits translation of A2 response element mRNAs
(2006) Molecular Biology of the Cell 8 (17) 3521-3533
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The microtubule-associated protein tumor overexpressed gene binds to the RNA trafficking protein heterogeneous nuclear ribonucleoprotein A2
(2005) Molecular Biology of the Cell 4 (16) 1938-1947
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pH microdomains in oligodendrocytes
(2004) Journal of Biological Chemistry 35 (279) 37115-37123
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A molecular mechanism for mRNA trafficking in neuronal dendrites
(2003) Journal of Neuroscience 26 (23) 8859-8866
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Anterograde RNA transport is inhibited in microtubule defective oligodendrocytes.
(2003) Mol. Cell Neurosci. (24) 926-38
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Facilitation of dendritic mRNA transport by CPEB
(2003) Genes and Development 5 (17) 638-653
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RNA transport in oligodendrocytes from the taiep mutant rat
(2003) Molecular and Cellular Neuroscience 4 (24) 926-938
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Intracellular trafficking of hnRNP A2 in oligodendrocytes
(2002) Experimental Cell Research 2 (279) 310-320
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RNA trafficking signals in human immunodeficiency virus type 1
(2001) Mol Cell Biol. 6 (21) 2133-43
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Mutational analysis of a heterogeneous nuclear ribonucleoprotein A2 response element for RNA trafficking
(1999) Journal of Biological Chemistry 48 (274) 34389-34395
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RNA on the road to myelin
(1999) Journal of Neurocytology 5-Apr (28) 263-270
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RNA on the road to myelin
(1999) Brain Cell Biology 5-Apr (28) 263-270
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The cis-acting RNA trafficking signal from myelin basic protein mRNA and its cognate trans-acting ligand hnRNP A2 enhance cap-dependent translation
(1999) Journal of Cell Biology 2 (147) 247-256
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Fluorescence quenching and dequenching analysis of RNA interactions in vitro and in vivo
(1998) Analytical Biochemistry 2 (264) 133-140
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hnRNP A2 selectively binds the cytoplasmic transport sequence of myelin basic protein mRNA
(1998) Biochemistry 19 (37) 7021-7029
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A general computational framework for modeling cellular structure and function
(1997) Biophysical Journal 3 (73) 1135-1146
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Rearrangement and reactivation of the myelin basic protein locus in myelin-deficient (mld) mouse brain
(1997) Journal of Neurochemistry 2 (68) 457-468
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Translations control and rna transport are mediated by the same clsitrans determinants
(1997) FASEB Journal 9 (11)
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Translocation of myelin basic protein mRNA in oligodendrocytes requires microtubules and kinesin
(1997) Cell Motility and the Cytoskeleton 4 (38) 318-328
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Transport and localization elements in myelin basic protein mRNA
(1997) Journal of Cell Biology 5 (138) 1077-1087
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Brain cytoplasmic and flagellar outer arm dyneins share a highly conserved M(r) 8,000 light chain
(1996) Journal of Biological Chemistry 32 (271) 19358-19366
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Calcium induced calcium release (CICR) and volume regulation in rabbit corneal cells
(1996) FASEB Journal 3 (10)
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Calcium Induced Calcium Release (CICR) involvement in Regulatory Volume Decrease (RVD) in rabbit corneal epithelial cells
(1996) Investigative Ophthalmology and Visual Science 3 (37)
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Localization of histidyl-tRNA synthetase (Jo-1) in human laryngeal epithelial carcinoma cell line (HEp-2 cells)
(1996) Cell and Tissue Research 3 (286) 487-491
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Protein translation components are colocalized in granules in oligodendrocytes
(1995) Journal of Cell Science 8 (108) 2781-2790
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Effects of hexagonal phase induction by dolichol on phospholipid membrane permeability and morphology
(1994) International Journal of Pharmaceutics 3 (105) 259-272
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Scanning concentration correlation spectroscopy using the confocal laser microscope
(1994) Biophysical Journal 2 I (66) 502-507
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Three-dimensional organization of endoplasmic reticulum in the ventral photoreceptors of Limulus
(1994) Journal of Comparative Neurology 2 (341) 172-183
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Transport and localization of exogenous myelin basic protein mRNA microinjected into oligodendrocytes
(1993) Journal of Cell Biology 2 (123) 431-441
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Molecular genetic analysis of the mld(r) mouse: A spontaneous revertant at the mld locus containing a recombinant myelin basic protein gene
(1992) Genetics 2 (130) 367-375
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Visualizing cells in three dimensions using confocal microscopy, image reconstruction and isosurface rendering: Application to glial cells in mouse central nervous system
(1992) Scanning Microscopy 2 (6) 345-357
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Diversification of glial lineages: a novel method to clone brain cells in vitro on nitrocellulose substratum.
(1991) Glia 3 (4) 256-268
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Cyclic AMP regulation of P0 glycoprotein and myelin basic protein gene expression in semi-differentiated peripheral neurinoma cell line D6P2T
(1989) Development 2 (106) 389-398
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Simultaneous imaging of cell and mitochondrial membrane potentials
(1989) Biophysical Journal 6 (56) 1053-1069
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Expression and localization of myelin basic protein in oligodendrocytes and transfected fibroblasts
(1988) Journal of Neurochemistry 6 (51) 1737-1745
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Expression of myelin basic protein mRNA and polypeptides in mouse oligodendrocytes in culture: Differential regulation by genetic and epigenetic factors
(1988) Developmental Brain Research 2 (39) 183-191
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Structure and expression of myelin basic protein gene sequences in the mld mutant mouse: reiteration and rearrangement of the MBP gene
(1987) Genetics 3 (116) 447-464
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Effect of the jimpy mutation on expression of myelin proteins in heterozygous and hemizygous mouse brain
(1984) Journal of Neurochemistry 6 (43) 1706-1715
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Myelin basic protein gene expression in quaking, jimpy, and myelin synthesis-deficient mice
(1984) Developmental Biology 1 (106) 38-44
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Developmental regulation of myelin basic protein expression in mouse brain
(1983) Developmental Biology 2 (96) 485-492
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Progenitors of oligodendrocytes: limiting dilution analysis in fetal rat brain culture
(1983) Developmental Biology 1 (96) 84-88
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The effect of the shiverer mutation on myelin basic protein expression in homozygous and heterozygous mouse brain
(1983) Journal of Neurochemistry 6 (40) 1680-1686
Book Chapters
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Oligodendrocyte differentiation: Quantitative studies in primary cultures of dissociated fetal rat brain
(1986) Glial-Neuronal Communication in Development and Regeneration, 737-754
Conference Papers
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Computational cell biologists snowed in at Cranwell
(2001) Trends in Cell Biology 6 (11) 236-238
Reviews
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Multiplexed RNA trafficking in oligodendrocytes and neurons
(2008) Biochimica et Biophysica Acta - Gene Regulatory Mechanisms 8 (1779) 453-458
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Rules of engagement promote polarity in RNA trafficking
(2006) BMC Neuroscience SUPPL. 1 (7)
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Systems analysis of RNA trafficking in neural cells
(2005) Biology of the Cell 1 (97) 51-62
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Fluorescence correlation spectroscopy and quantitative cell biology
(2004) Differentiation 1 (72) 1-10
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Computational cell biology: Spatiotemporal simulation of cellular events
(2002) Annual Review of Biophysics and Biomolecular Structure (31) 423-441
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RNA trafficking in oligodendrocytes.
(2001) Results and problems in cell differentiation (34) 69-81
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The balance of power in RNA trafficking
(2001) Current Opinion in Neurobiology 5 (11) 558-563
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RNA trafficking in myelinating cells
(1998) Current Opinion in Neurobiology 5 (8) 607-612