James I. Morgan, PhD

    James I. Morgan, PhD

    Member, St. Jude Faculty
    Chair, Developmental Neurobiology
    Shahdam, Edna and Albert Abdo Basic Science Chair

    Departments

    Developmental Neurobiology

    Contact Information

    James Morgan, PhD
    Developmental Neurobiology
    MS 323, Room D2025E
    St. Jude Children's Research Hospital
    262 Danny Thomas Place
    Memphis, TN 38105-3678
    Email: jim.morgan@stjude.org
    Phone: (901) 595-2256
    FAX: (901) 595-3143

    Education

    PhD - University of Aston, Birmingham, England


    Research Interests

    Research in this laboratory is aimed at providing an understanding of the molecular mechanisms that contribute to normal and pathological neuronal death and differentiation. In adult and developing animals, nerve cells and their precursors are confronted with a series of decisions involving choices such as exiting the cell cycle, undergoing apoptosis or differentiation, migrating and establishing, maintaining and modifying their correct synaptic connections. Perturbations in these processes have profound consequences and result in a wide range of pathological outcomes such as brain tumors, epilepsy, mental retardation, Parkinson’s and Alzheimer’s diseases. We employ the tools of contemporary molecular biology, genomics and cellular imaging in models of aberrant neuronal death and differentiation to identify the genes that play critical roles in these processes. The products of these genes and the pathways in which they function become targets for novel therapeutic strategies aimed at preventing or ameliorating human diseases of the nervous system.

    Current research in the laboratory focuses upon investigating genes and signaling pathways that contribute to: (1) neuronal death (Nna1) and (2) synaptic stability (Cbln1) in the developing cerebellum. Nna1 is the defective gene in the Purkinje cell degeneration cerebellar mutant, and encodes an intracellular zinc carboxypeptidase that removes glutamate from polyglutamylated proteins. This provides the first link between this unusual form of post-translational modification and neuronal survival. Cbln1 is the prototype of a family of secreted TNF-related proteins that regulate synaptic stability and neuronal survival in developing cerebellum. These proteins serve as bi-functional ligands that bridge presynaptic neurexins on cerebellar granule neurons to the postsynaptic orphan glutamate receptor, Grid2 on Purkinje cells.


    Selected Publications

    Wu HY, Wang T, Li L, Correia K, Morgan JI. A structural and functional analysis of Nna1 in Purkinje cell degeneration (pcd) mice. FASEB J 26:4468-4480, 2012.

    Pattarini R, Rong Y, Shepherd KR, Jiao Y, Qu C, Smeyne RJ, Morgan JI. Long lasting transcriptional refractoriness triggered by a single explsure to 1-methyl-4-phenyl-1,2,3,6- tetrahydropyrimidine. Neuroscience 214:84-105, 2012.

    Morgan MA, Morgan JI. Pcp4|1 contains an auto-inhibitory element that prevents its IQ motif from binding to calmodulin. J Neurochem 121:843-851, 2012.

    Wei P, Pattarini R, Rong Y, Guo H, Bansal PK, Kusnoor SV, Deutch AY, Parris J, Morgan JI. The Cbln family of proteins interact with multiple signaling pathways. J Neurochem 121:717-729, 2012.

    Rong Y, Wei P, Parris J, Guo H, Pattarini R, Correia K, Li L, Kusnoor SV, Deutch AY, Morgan JI. Comparison of Cbln1 and Cbln2 functions using transgenic and knockout mice. J Neurochem 120:528-540, 2012.

    Wei P, Blundon JA, Rong Y, Zakharenko SS, Morgan JI. Impaired Locomotor Learning and Altered Cerebellar Synaptic Plasticity in pep-19/pcp4-Null Mice. Mol Cell Biol 31:2838-2844, 2011. (Featured in Mol Cell Bio Spotlight 31(14):2773).

    Kusnoor SV, Parris J, Muly ED, Morgan JI, Deutch AY. Extracerebellar role for cerebellin1: modulation of dendritic spine density and synapses in striatal medium spiny neurons. J Comp Neurol 518:2525-37, 2010.

    Wei P, Rong Y, Li L, Bao D, Morgan JI. Characterization of trans-neuronal trafficking of Cbln1. Mol Cell Neurosci Jun;41(2):258-73, 2009. Epub 2009 Apr 1.

    Pattarini R, Rong Y, Qu C, Morgan JI. Distinct mechanisms of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyrimidine resistance revealed by transcriptome mapping in mouse striatum. Neuroscience Sep 9;155(4):1174-94, 2008. Epub 2008 Jul 8.

    Pattarini R, Smeyne RJ, Morgan JI. Temporal mRNA profiles of inflammatory mediators in the murine 1‑methyl‑4‑phenyl‑1,2,3,6‑tetrahydropyrimidine model of Parkinson’s disease. Neuroscience 145:654-668, 2007.

    Pattarini R, Rong Y, Qu C, Morgan JI. Distinct mechanisms of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyrimidine resistance revealed by transcriptome mapping in mouse striatum. Neuroscience Sep 9;155(4):1174-94, 2008. Epub 2008 Jul 8.

    Wei P, Smeyne R, Bao D, Parris J, Morgan JI. Mapping of Cbln1-like immunoreactivity in adult and developing mouse brain and its localization to the endolysosomal compartment of neurons. Eur J Neurosci 26:2962-2978, 2007.

    Bao D, Pang Z, Morgan MA, Parris, J, Rong Y, Li L, Morgan JI. Cbln1 is essential for interaction-dependent secretion of Cbln3. Mol Cell Biol 26:9327-9337, 2006.

    Wang T, Parris J, Li L, Morgan JI. The carboxypeptidase-like substrate-binding site in Nna1 is essential for the rescue of the Purkinje cell degeneration (pcd) phenotype. Mol Cell Neurosci 33:200-213, 2006.

    Hirai H, Pang Z, Bao D, Miyazaki T, Li L, Miura E, Parris J, Rong Y, Watanabe M, Yuzaki M, Morgan JI. Cbln1 is essential for synaptic integrity and plasticity in the cerebellum. Nat Neurosci 8(11):1534-1541, 2005. (Featured in Nat Neurosci News and Views 8(11):1417-1418.)

    Bao D, Pang Z, Morgan JI. The structure and proteolytic processing of Cbln1 complexes. J Neurochem 95:618-629, 2005.

    Li L, Connelly MC, Wetmore C, Curran T, Morgan JI. Mouse embryos cloned from brain tumors. Cancer Res 63:2733-2736, 2003.

    Fernandez-Gonzalez A, La Spada AR, Treadaway J, Higdon JC, Harris BS, Sidman RL, Morgan JI, Zuo J. Purkinje cell degeneration (pcd) phenotypes caused by mutations in the axotomy-induced gene, Nna1. Science 295:1904-1906, 2002.

    Harris A, Morgan JI, Pecot M, Soumare A, Osborne A, Soares HD. Regenerating motor neurons express Nna1, a novel ATP/GTP-binding protein related to zinc carboxypeptidases. Mol Cell Neurosci 16:578-596, 2000.

    Pang Z, Zuo J, Morgan JI. Cbln3, a novel member of the precerebellin family that binds specifically to Cbln1. J Neurosci 20:6333-6346, 2000.

    Herzog K-H, Chong MJ, Kapsetaki M, Morgan JI, McKinnon PJ. Requirement for Atm in ionizing radiation-induced cell death in the developing central nervous system. Science 280:1089-1091, 1998.

    Mandelzys A, Gruda MA, Bravo R, Morgan JI. Absence of a persistently elevated 37 kDa Fos-related antigen and AP-1-like DNA-binding activity in the brains of kainic acid-treated fosB null mice. J Neurosci 17:5407-5415, 1997.

    D'Arcangelo G, Miao GG, Chen S-C, Soares HD, Morgan JI, Curran T. A protein related to extracellular matrix proteins deleted in the mouse mutant reeler. Nature 374:719-723, 1995.

    Oberdick J, Schilling K, Smeyne RJ, Corbin JG, Bocchiaro C, Morgan JI. Control of segment-like patterns of gene expression in the mouse cerebellum. Neuron 10:1007-1018, 1993.

    Smeyne RJ, Vendrell M, Hayward M, Baker SJ, Miao GG, Schilling K, Robertson LM, Curran T, Morgan JI. Continuous c-fos expression precedes programmed cell death in vivo. Nature 363:166-169, 1993.

    Smeyne RJ, Schilling K, Robertson L, Luk D, Oberdick J, Curran T, Morgan JI. Fos-lacZ transgenic mice: mapping sites of gene induction in the central nervous system. Neuron 8:13-23, 1992.

    Smeyne RJ, Oberdick J, Schilling K, Berrebi AS, Mugnaini E, Morgan JI. Dynamic organization of developing Purkinje cells revealed by transgene expression. Science 254:719-721, 1991.

    Schilling K, Dickinson MH, Connor JA, Morgan JI. Electrical activity in cerebellar cultures determines Purkinje cell dendritic growth patterns. Neuron 7:891-902, 1991.

    Oberdick J, Smeyne RJ, Mann JR, Zackson S, Morgan JI. A promoter that drives transgene expression in cerebellar Purkinje and retinal bipolar neurons. Science 248:223-226, 1990.

    Sonnenberg JL, Macgregor-Leon PF, Curran T, Morgan JI. Dynamic alterations occur in the levels and composition of transcription factor AP-1 complexes after seizure. Neuron 3:359-365, 1989.

    Morgan JI, Cohen DR, Hempstead JL, Curran T. Mapping patterns of c-fos expression in the central nervous system after seizure. Science 237:192-197, 1987.

    Morgan JI, Curran T. Role of ion flux in the control of c-fos expression. Nature 322:552-555, 1986.

    Curran T, Morgan JI. Superinduction of c-fos by nerve growth factor in the presence of peripherally active benzodiazepines. Science 229:1265-1268, 1985.

    Last updated: February 2013