Thomas Jefferson University - Koichi Iijima, Ph.D.
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Qualifications
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Ph. D., The University of Tokyo, Pharmaceutical Sciences, 2001
Postdoctoral training, Cold Spring Harbor Laboratory, Genetics and Neuroscience, 2001-2006
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Expertise and Research Interests
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Alzheimer disease (AD) is a progressive neurodegenerative disease and the most common form of senile dementia. Pathologically, AD is defined by the formation of two characteristic protein aggregates in the autopsied brains: amyloid deposits and neurofibrillary tangles. Accumulating evidence suggests that the amyloid-beta 42 (Abeta42) peptide, a major component of amyloid deposits, plays a causative role in the pathogenesis of AD. However, it remains elusive how Abeta42 does so.
My laboratory is interested to understand how Abeta42, a small and misfolding-prone peptide, can induce a variety of neurotoxicity in the brains. In order to systematically identify genes and pathways that are involved in Abeta42-induced neurotoxicity in brains, we are using a fruit fly, Drosophila as an efficient model system. Many genes and cellular pathways are remarkably conserved between a human and a fly, and Drosophila has been used to study various aspects of human biology including cognitive functions and aging process. We demonstrated that overexpression of human Abeta42 in fly brains recapitulated many important features of AD, including progressive memory defects, locomotor dysfunction, neurodegeneration, and amyloid deposits formation indicating that a Drosophila served as a model to investigate the complex toxicity of Abeta42 in vivo.
In a close collaboration with Dr. Kanae Iijima-Ando, we took two complementary genome-wide approaches in Abeta42 flies: a genetic screen and a microarray based gene expression analysis. Through these analyses, we have identified several genes and pathways that could modify Abeta42-induced neurotoxicity. Detailed analysis of these genes and pathways will facilitate our understanding of complex AD pathogenesis and lead to a discovery of novel therapeutic targets for AD.
Also, in a collaboration with Dr. Kanae Iijima-Ando, we are investigating the physiological functions of, and mechanisms underlying circadian oscillation of the cyclic AMP responsive element (CRE)-binding protein (CREB) activity in Drosophila.
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Keywords
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Alzheimer disease, Tauopathies, neurodegenerative diseases, metabolic disease, energy metabolism, circadian rhythm, neurogenetics, gene expression, Drosophila
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Publications
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- Iijima, K., Zhao, L., Shenton, C., and Iijima-Ando, K. Regulation of energy stores and feeding by neuronal and peripheral CREB activity in Drosophila, Submitted
- Iijima-Ando, K. and Iijima, K. (2010) Transgenic Drosophila models of Alzheimer's disease and tauopathies, (review article), Brain Struct Funct, in press
- Iijima-Ando, K., Hearn, S.A., Shenton, C., Gatt, A., Zhao, L. and Iijima, K. (2009) Mitochondrial mislocalization underlies Abeta42-induced neuronal dysfunction in a Drosophila model of Alzheimer's disease, PLoS ONE, in press
- Lee, K-S., Iijima-Ando, K., Iijima, K., Lee, W-J., Lee, J.H., Yu, K., and Lee, D-S. (2009) JNK/FOXO-mediated neuronal expression of fly homologue of Peroxiredoxin II reduces oxidative stress and extends lifespan in Drosophila, J. Biol. Chem., 284, 29454-61
- Iijima, K., Iijima-Ando, K., and Zhong, Y. (2009) Drosophila model of Alzheimer's amyloidosis, Chapter 14, Handbook of Behavior Genetics, Springer
- Chiang, H., Iijima, K., Hakker, I., and Zhong, Y. (2009) Distinctive roles of different beta-amyloid 42 aggregates in modulation of synaptic functions. FASEB J, 23(6):1969-77
- Iijima, K., and Iijima-Ando, K. (2008) Drosophila models of Alzheimer amyloidosis; the challenge of dissecting the complex mechanisms of toxicity of amyloid-beta 42. (Review article) Journal of Alzheimer Disease, 15(4):523-40
- Iijima-Ando, K., Hearn, S.A., Granger, L., Shenton, C., Gatt, A., Chiang, H.C., Hakker, I., Zhong, Y., and Iijima, K. (2008). Overexpression of Neprilysin Reduces Alzheimer Amyloid beta-42 (Abeta42)-induced Neuron Loss and Intraneuronal Abeta42 Deposits but Causes a Reduction in cAMP-responsive Element-binding Protein-mediated Transcription, Age-dependent Axon Pathology, and Premature Death in Drosophila. J. Biol. Chem. 283, 19066-19076 (highlighted by ASBMB)
- Iijima, K., Chiang, H. C., Hearn, S. A., Hakker, I., Gatt, A., Shenton, C., Granger, L., Leung, A., Iijima-Ando, K., and Zhong, Y. (2008) Abeta42 mutants with different aggregation profiles induce distinct pathologies in Drosophila. PLoS ONE 3, e1703
- Sano, Y., Nakaya, T., Pedrini, S., Furukori, K., Iijima-Ando, K., Iijima, K., Mathews, P.M., Itohara, S., Gandy, S, and Suzuki, T. (2006) Physiological mouse brain amyloid-beta levels are not related to the phosphorylation state of threonine-668 of Alzheimer APP. PLoS ONE, 1, e51
- Iijima-Ando, K., Wu, P., Drier, A., Iijima, K. & Yin, J.C.P. (2005) CREB and HSP70 additively suppress polyglutamine-induced toxicity in Drosophila. Proc. Natl. Acad. Sci. 102, 10261-6
- Asaumi, M., Iijima, K., Sumioka, A.,Iijima-Ando, K., Kirino, Y., Nakaya, T. & Suzuki, T. (2005) Interaction of N-terminal acetyltransferase with the cytoplasmic domain of beta-amyloid precursor protein and its effect on Abeta secretion. J. Biochem. (Tokyo). 137(2):147-55
- Iijima, K., Liu, H-P., Chiang, A-S., Hearn, S. A., Konsolaki, M. & Zhong, Y. (2004) Dissecting the pathological effects of human Abeta40 and Abeta42 in Drosophila: A potential model for Alzheimer disease. Proc. Natl. Acad. Sci. 101, 6623-6628
- Taru, H., Iijima, K., Hase, M., Kirino, Y., Yagi, Y., & Suzuki, T. (2002) Interaction of Alzheimer beta-Amyloid Precursor Family Proteins with Scaffold Proteins of the JNK Signaling Cascade. J. Biol. Chem. 277, 20070-78
- Ando, K., Iijima, K., Elliott, J.L., Kirino, Y., & Suzuki, T. (2001) Phosphorylation-dependent regulation on the interaction of amyloid precursor protein with Fe65 and the production of beta-amyloid. J. Biol. Chem. 276, 40353-61
- Iijima, K., Ando, K., Takeda, S., Satoh, Y., Seki, T., Itohara, S., Greengard, P., Narin, A.C., Kirino, Y. & Suzuki, T. (2000). Neuron-specific phosphorylation of Alzheimer amyloid precursor protein by Cdk5. J. Neurochem. 75, 1085-91
- Suzuki, T., Ando, K., Iijima, K., Oguchi, S., Takeda, S. (1999). Phosphorylation of Amyloid Precursor Protein (APP) Family Proteins. Alzheimers Disease Methods and Protocols, Methods in Molecular Medicine, Vol 32, 271-282
- Ando, K., Oishi, M., Takeda, S., Iijima, K., Isohara, T., Narin, A.C., Kirino, Y., Greengard, P., & Suzuki, T. (1999). Role of phosphorylation of Alzheimer amyloid precursor protein during neuronal differentiation. J Neurosci. 19, 4421-7
- Watanabe,T., Sukegawa, J., Sukegawa, I., Tomita, S., Iijima, K., Oguchi, S., Suzuki, T., Nairn, A.C., & Greengard, P. (1999). A 127-kDa protein (UV-DDB) binds to the cytoplasmic domain of the Alzheimer amyloid precursor protein. J. Neurochem. 72, 549-56
- Iijima, K, Lee, D.S., Okutsu, J., Tomita, S., Hirashima, N., Kirino, Y., & Suzuki, T. (1998) cDNA isolation of Alzheimer amyloid precursor protein from cholinergic nerve terminals of the electric organ of the electric ray. Biochem. J. 330, 29-33
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Individual Expertise profile of
Koichi Iijima, Ph.D., Copyright © Koichi Iijima, Ph.D..
Last Updated
by Koichi Iijima, Ph.D. : Saturday, November 21, 2009 12:31:42 PM
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