Our research goal is to elucidate disease causalities and their patho-etiologies, and ultimately to develop therapeutic tool. With the advent of next generation sequencing technologies, it becomes very handy to identify causalities of monogenic diseases as well as complex diseases. With the vast of genomic information at hand, we will combine gene expression profiles of the responsible tissues together with clinical information to understand the global picture of diseases.
Graphical representation for retrograde hypothesis of the origin of endometriosis according to the results of this study. Endometriosis and uterine endometrium harbor cancer-associated somatic mutations. Endometrial glands carry distinct mutations of cancer-associated genes such as KRAS and PIK3CA. Retrograde flow of endometrial cells harboring cancer-associated mutations have selective advantages and go through clonal expansion at ectopic sites (peritoneal surface and ovary), leading to the development of endometriosis.
Romero V, Nakaoka H, Hosomichi K, Inoue I. High Order Formation and Evolution of Hornerin in Primates. Genome Biol Evol. 2018 Dec 1;10(12):3167-3175.
Suda K, Nakaoka H, Yoshihara K, Ishiguro T, Tamura R, Mori Y, Yamawaki K, Adachi S, Takahashi T, Kase H, Tanaka K, Yamamoto T, Motoyama T, Inoue I, Enomoto T. Clonal Expansion and Diversification of Cancer-Associated Mutations in Endometriosis and Normal Endometrium. Cell Rep. 2018 Aug 14;24(7):1777-1789.
Ito J, Sugimoto R, Nakaoka H, Yamada S, Kimura T, Hayano T, Inoue I. Systematic identification and characterization of regulatory elements derived from human endogenous retroviruses. PLoS Genet. 2017 Jul 12;13(7):e1006883.
Hirata J, Hosomichi K, Sakaue S, Kanai M, Nakaoka H, Ishigaki K, Suzuki K, Akiyama M, Kishikawa T, Ogawa K, Masuda T, Yamamoto K, Hirata M, Matsuda K, Momozawa Y, Inoue I, Kubo M, Kamatani Y, Okada Y. Genetic and phenotypic landscape of the major histocompatibilty complex region in the Japanese population. Nat Genet. 2019 Jan 28. doi: 10.1038/s41588-018-0336-0. [Epub ahead of print].