Our research goal is to elucidate disease causalities and their patho-mechanisms, 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.
Kawamura Y, Nakaoka H, Nakayama A, Okada Y, Yamamoto K, Higashino T, Sakiyama M, Shimizu T, Ooyama H, Ooyama K, Nagase M, Hidaka Y, Shirahama Y, Hosomichi K, Nishida Y, Shimoshikiryo I, Hishida A, Katsuura-Kamano S, Shimizu S, Kawaguchi M, Uemura H, Ibusuki R, Hara M, Naito M, Takao M, Nakajima M, Iwasawa S, Nakashima H, Ohnaka K, Nakamura T, Stiburkova B, Merriman TR, Nakatochi M, Ichihara S, Yokota M, Takada T, Saitoh T, Kamatani Y, Takahashi A, Arisawa K, Takezaki T, Tanaka K, Wakai K, Kubo M, Hosoya T, Ichida K, Inoue I, Shinomiya N, Matsuo H. Genome-wide association study revealed novel loci which aggravate asymptomatic hyperuricaemia into gout. Ann Rheum Dis. 2019 Oct;78(10):1430-1437.
Suda K, Nakaoka H, Hata C, Yahata N, Isobe M, Kameyama H, Wakai T, Motoyama T, Inoue I, Yoshihara K, Enomoto T. Concurrent isolated retroperitoneal HGSC and STIC defined by somatic mutation analysis: a case report. Diagn Pathol. 2019 Feb 11;14(1):17.
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 MHC region in the Japanese population. Nat Genet 3, 470-480, 2019.
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 CancerAssociated Mutations in Endometriosis and Normal Endometrium. Cell Rep. 2018 Aug 14;24(7):1777-1789.