Koichi Iijima, PhD
Philadelphia, PA 19107
(215) 955-4949 fax
Most Recent Peer-reviewed Publications
- Transgenic drosophila models of Alzheimer's amyloid-β 42 toxicity
- Tau Ser262 phosphorylation is critical for Aβ42-induced tau toxicity in a transgenic Drosophila model of Alzheimer's disease
- Transgenic drosophila models of Alzheimer's disease and tauopathies
- A DNA damage-activated checkpoint kinase phosphorylates tau and enhances tau-induced neurodegeneration
- Mitochondrial mislocalization underlies aβ42-induced neuronal dysfunction in a drosophila model of alzheimer's disease
Research and Clinical Interests
Alzheimer's disease, Tauopathies, Drosophila Neurobiology
Alzheimer's disease (AD) is the most common senile dementia characterized by formation of amyloid deposits (APs) and loss of neurons in the brain parenchyma. Although the amyloid-b42 (Ab42) peptide, which is a major component of APs, has been suggested to play a central role in the pathogenesis of AD, molecular mechanisms underlying Ab42-induced toxicity in brains are not well understood. My research focuses on identifying genes and molecular pathways that are involved in toxic effects of Ab42 in vivo..
We utilize a fruit fly, Drosophila, as a primary model system. Many genes and cellular pathways are conserved between a human and a fly, and Drosophila has been used to study various aspects of human biology including learning and memory. We demonstrated that overexpression of human Ab42 peptide in fly brains recapitulated many important features of AD, including progressive memory defects, locomotor dysfunction and neurodegeneration, indicating that a Drosophila served as a model to investigate the toxicity of Ab42 in vivo. One of the most important tools that Drosophila provides is the ability to carry out large-scale genetic screens for mutations that affect a given process. Through genome-wide genetic screen and DNA microarray analysis in our fly model, we are aiming to identify "druggable genes" that suppress Ab42-induced memory defects and neurodegeneration.
We recently identified several candidate genes and molecular pathways, which can modify the toxicity of Ab42 in fly brains. Detailed functional analysis of these genes and pathways in fly and higher mammalian model systems will greatly advance our understanding of AD and will lead to the discovery of novel therapeutic targets for AD.