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Graduate School
Ph. D., The University of Tokyo, Tokyo, Japan
Fellowship
Postdoctoral fellow, Cold Spring Harbor Laboratory
Board Certification
Ph. D., The University of Tokyo, Tokyo, Japan
University Appointment
Assistant Professor (2006)
Research and Clinical Interests
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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Koichi Iijima, Ph.D.