Great challenges in molecular medicine: toward personalized medicine

GENE HUNTING, SIGNALING NETWORK, AND MOLECULAR MEDICINE In the 20th century, most researchers investigated WNT signaling in cell and developmental biology by using model animals, such as Drosophila, Xenopus, and mouse. However, I was confident that WNT signaling should be investigated for clinical application by using human samples or cell lines. In 1998, I, together with post-doctoral fellows, started a human WNTome project to comprehensively clone and characterize novel human genes encoding WNT signaling molecules and to establish a “human WNT research” platform (Figure 1A). My group reported the molecular cloning and characterization of FZD1, FZD3, FZD4, FZD6, FZD7, FZD8, FZD10, GIPC2, GIPC3, MFRP, NKD1, NKD2, VANGL1, WNT3A, WNT5B, WNT6, WNT7B, WNT8A, WNT9A (WNT14), WNT9B (WNT14B), and WNT10A as the major products of the human WNTome project [reviewed in Katoh (2002a)] and of other novel human genes, such as FGF20, RhoU, RhoV, and SOX17, as byproducts of the human WNTome project. Most human genes that encode WNT signaling components had been cloned and characterized by 2002, whereas thousands of novel human genes outside of the WNT field still remained to be discovered. In 2003, colleagues and I started a post-WNTome project to identify and characterize novel human genes encoding adhesion molecules, transmembrane proteins, epigenetic regulators, and transcription factors (Figure 1A). My group reported in silico identification and characterization of novel human genes, such as ANO1 (TMEM16A), ANO2 (TMEM16B), ANO3 (TMEM16C), ANO4 (TMEM16D), ANO5 (TMEM16E), ANO6 (TMEM16F), ANO7 (TMEM16G), ANO8 (TMEM16H), ASXL2, ASXL3, BCL9L, CDC50A (TMEM30A), CDC50B (TMEM30B), CDC50C (TMEM30C), CRB2, DACT1 (DAPPER1), DACT2 (DAPPER2), DIXDC1, FAT4, FMNL1, FMNL2, FMNL3, FOXR1 (FOXN5), FOXR2 (FOXN6), HES2, HES3, HES5, JMJD1C (TRIP8), JMJD2A (KDM4A), JMJD2B (KDM4B), JMJD2C (KDM4C), JMJD2D (KDM4D), KIF27, MPP7, PRICKLE1, and PRICKLE2. The human WNTome and postWNTome projects were gene-hunting adventures that utilized molecular biology and computational biology, respectively. Interand intra-cellular signaling networks were simplified to a secondary picture consisting of nodes and edges. Nodes correspond to genes, mRNAs, proteins, or micro-RNAs (miRNAs), while edges correspond to their interactions. I then shifted my interest from the nodes to the edges and the whole picture. In 2007, my laboratory started a stem-cell signaling network project to elucidate mutual interactions of the WNT, FGF, Notch, Hedgehog, TGF-β, and BMP signaling cascades (Figure 1A) (Katoh and Katoh, 2007, 2009; Katoh and Nakagama, 2013). Recently, I was appointed as the chief editor of Frontiers in Molecular Medicine, a subor specialty journal of Frontiers in Cell and Developmental Biology. I would like to contribute to the global scientific community through Frontiers in Molecular Medicine, which aims to address the gap between cell and developmental biology and clinical medicine and to promote development of novel diagnostics and therapeutics for a variety of human diseases, including cancers, cardiovascular diseases, diabetes mellitus, eye diseases, inflammatory bowel diseases, kidney diseases, liver diseases, neurological diseases, and respiratory diseases.