Position title: Professor
Identifying genes involved in aging, cell proliferation and neovascularization using mouse genetics
- 5322 Genetics/Biotech
- Ph.D., University of Tokyo (1997), Postdoctoral Research: The Jackson Laboratory, 1997-2003
- Medical Genetics
- Research Interests
- Our laboratory aims to identify genes involved in aging and age-related diseases using mouse genetics as a tool
- Research Fields
- Disease Biology Cell Biology, Gene Expression, Neuro & Behavioral Genetics, Human, mouse & rat
Our research program is aimed at understanding the molecular mechanisms causing age-dependent abnormalities and its association with age-related diseases. Our studies have shown that mouse models showing accelerated aging phenotypes provide powerful tools to investigate these mechanisms. The experimental system for most of our studies is the mouse eye, which offers a number of advantages: The eye is not a vital organ so mutations affecting the processes of interest can be identified and studied throughout the entire span of development. The well-organized structure and easy accessibility of the eye facilitate experimental analyses. At the same time, because the cells present in the eye (e. g. epithelial cells, neurons, inflammatory cells) are representative of cell types present in other organs, information gained from studies on the eye can reveal cellular mechanisms of general significance. In general, our studies utilize a forward genetic approach, beginning with mouse mutants that manifest phenotypes of interest (accelerated aging). A major advantage of this phenotype-driven approach is that it offers the potential of identifying previously unknown genes and molecular pathways that regulate a process of interest. After a gene/protein of interest has been identified, we aim to unravel the pathway by which it normally acts whose disruption results in the observed phenotype. One major approach we use in dissecting these pathways is to identify genetic modifiers that interact with the original mutation indicating that they are likely to be affecting other components in the same pathway. In this way, we can expand beyond the original mutation to obtain additional entry points into the same pathway and allow a more complete understanding of the molecular pathways that underlie the phenotypes under investigation.
Over the past years, we have used these approaches to identify and characterize several genes of interest and to begin to elucidate the pathways through which they operate. Our immediate future goals are to obtain a more detailed understanding of these pathways to advance our understanding of the mechanisms that regulate aging and underlie age-related diseases.
Search PubMed for more publications by Akihiro Ikeda
Lee WH, Bhute VJ, Higuchi H, Ikeda S, Palecek SP, Ikeda A. 2020. Metabolic Alterations Caused by the Mutation and Overexpression of the Tmem135 Gene. Exp Biol Med (Maywood). Jun 9:1535370220932856. doi: 10.1177/1535370220932856.
Macke EL, Henningsen E, Jessen E, Zumwalde NA, Landowski M, Western DE, Lee WH, Liu C, Gruenke NP, Doebley AL, Miller S, Pattnaik B, Ikeda S, Gumperz JE, Ikeda A. 2020. Loss of chondroitin sulfate modification causes inflammation and neurodegeneration in skt mice. Genetics. 214(1):121-134.
Lewis SA, Takimoto T, Mehrvar S, Higuchi H, Doebley AL, Stokes G, Sheibani N, Ikeda S, Ranji M, Ikeda A. 2018. The effect of Tmem135 overexpression on the mouse heart. PLoS One. 13(8):e0201986.
Lee WH, Higuchi H, Ikeda S, Macke EL, Takimoto T, Pattnaik BR, Liu C, Chu LF, Siepka SM, Krentz KJ, Rubinstein CD, Kalejta RF, Thomson JA, Mullins RF, Takahashi JS, Pinto LH, Ikeda A. 2016. Mouse Tmem135 mutation reveals a mechanism involving mitochondrial dynamics that leads to age-dependent retinal pathologies. eLife. doi: 10.7554/eLife.19264
Higuchi H, Macke EL, Lee WH, Miller SA, Xu JC, Ikeda S, Ikeda A. 2015. Genetic basis of age-dependent synaptic abnormalities in the retina. Mamm Genome. 26:21-32.