Hiroyuki ABURATANI

RESEARCH DIRECTIONS

Dissect biomedical phenomena with advanced genomic technologies

LABORATORY

https://www.genome.rcast.u-tokyo.ac.jp/

PROFILE

1980- Medical School, The University of Tokyo (UTokyo)

1980- Third Department of Internal Medicine, UTokyo Hospital

1983- Research Associate, Third Department of Internal Medicine, UTokyo Hospital

1988- Research Fellow, MIT Center for Cancer Research

1995- Research Associate, Third Department of Internal Medicine, UTokyo Hospital

1999- Associate Professor, RCAST, UTokyo

2001- Professor, RCAST, UTokyo

2002- Professor, Center for Collaborative Research, UTokyo

2006- Professor, RCAST, UTokyo

2021- Senior Research Fellow, RCAST, UTokyo

FIELD OF INTEREST

We are working with systems biology and medicine to understand complex biological systems through a functional genomics approach. High throughput technology and novel algorithms are required for collecting, integrating and visualizing the enormous amount of data on gene expression, protein expression, and protein interactions arising in the wake of the Human Genome Project. Alliance with external academics and industry will be crucial to the success of the new “systems biology”, that is, understanding biological systems as more than the sum of their parts.

1. Personal cancer genome

The variety of genetic and epigenetic alterations that accumulate in cancer genomes cause activation of oncogenes and inactivation of tumor suppressor genes, leading to cellular transformation. Next generation sequencing technology has enabled us to obtain individual genomic information within feasible cost and time constraints. Since 2008 my group have participated in the International Cancer Genome Consortium and are studying the genomic alterations in liver and pancreatic cancer.

2. Epigenomics

Epigenetic processes are essential for the packaging and interpretation of the genome, fundamental to normal development and cell differentiation, and increasingly recognized as being involved in human disease. Epigenetic mechanisms, which include histone modification, positioning of histone variants, nucleosome remodelling, DNA methylation, and non-coding RNAs, are considered as “cellular memory”. We have applied genomic technologies, such as ChIP-sequencing, to map these epigenetic marks throughout the genome and to elucidate how these marks are written and read.

3. Translational research

Functional genomic approaches are applied to identify novel biomarkers for disease diagnostics and therapeutics.

PUBLICATION

High-throughput single-molecule RNA imaging analysis reveals heterogeneous responses of cardiomyocytes to hemodynamic overload. Satoh M, Nomura S, Harada M, Yamaguchi T, Ko T, Sumida T, Toko H, Naito AT, Takeda N, Tobita T, Fujita T, Ito M, Fujita K, Ishizuka M, Kariya T, Akazawa H, Kobayashi Y, Morita H, Takimoto E, Aburatani H, Komuro I.J. Mol. Cell. Cardiol. 2019 03;128:77-89. doi: 10.1016/j.yjmcc.2018.12.018 Identification of MYLK3 mutations in familial dilated cardiomyopathy. Tobita T, Nomura S, Morita H, Ko T, Fujita T, Toko H, Uto K, Hagiwara N, Aburatani H, Komuro I.Sci Rep. 2017 12 13;7(1):17495. doi: 10.1038/s41598-017-17769-1 Extracellular Acidic pH Activates the Sterol Regulatory Element-Binding Protein 2 to Promote Tumor Progression. Kondo A, Yamamoto S, Nakaki R, Shimamura T, Hamakubo T, Sakai J, Kodama T, Yoshida T, Aburatani H, Osawa T.Cell Rep. 2017 02 28;18(9):2228-2242. doi: 10.1016/j.celrep.2017.02.006 TET2 functions as a resistance factor against DNA methylation acquisition during Epstein-Barr virus infection. Namba-Fukuyo H, Funata S, Matsusaka K, Fukuyo M, Rahmutulla B, Mano Y, Fukayama M, Aburatani H, Kaneda A.Oncotarget. 2016 Dec 06;7(49):81512-81526. doi: 10.18632/oncotarget.13130 CASTIN: a system for comprehensive analysis of cancer-stromal interactome. Komura D, Isagawa T, Kishi K, Suzuki R, Sato R, Tanaka M, Katoh H, Yamamoto S, Tatsuno K, Fukayama M, Aburatani H, Ishikawa S.BMC Genomics. 2016 11 09;17(1):899. doi: 10.1186/s12864-016-3207-z Network-based analysis for identification of candidate genes for colorectal cancer progression. Tsuji S, Midorikawa Y, Seki M, Takayama T, Sugiyama Y, Aburatani H.Biochem. Biophys. Res. Commun. 2016 08 05;476(4):534-540. doi: 10.1016/j.bbrc.2016.05.158 RHOA mutation in diffuse-type gastric cancer: a comparative clinicopathology analysis of 87 cases. Ushiku T, Ishikawa S, Kakiuchi M, Tanaka A, Katoh H, Aburatani H, Lauwers GY, Fukayama M.Gastric Cancer. 2016 Apr;19(2):403-411. doi: 10.1007/s10120-015-0493-0 Recurrent gain-of-function mutations of RHOA in diffuse-type gastric carcinoma. Kakiuchi M, Nishizawa T, Ueda H, Gotoh K, Tanaka A, Hayashi A, Yamamoto S, Tatsuno K, Katoh H, Watanabe Y, Ichimura T, Ushiku T, Funahashi S, Tateishi K, Wada I, Shimizu N, Nomura S, Koike K, Seto Y, Fukayama M, Aburatani H, Ishikawa S.Nat. Genet. 2014 Jun;46(6):583-7. doi: 10.1038/ng.2984 Multilayer-omics analysis of renal cell carcinoma, including the whole exome, methylome and transcriptome. Arai E, Sakamoto H, Ichikawa H, Totsuka H, Chiku S, Gotoh M, Mori T, Nakatani T, Ohnami S, Nakagawa T, Fujimoto H, Wang L, Aburatani H, Yoshida T, Kanai Y.Int. J. Cancer. 2014 Sep 15;135(6):1330-42. doi: 10.1002/ijc.28768 ROBO1, a tumor suppressor and critical molecular barrier for localized tumor cells to acquire invasive phenotype: study in African-American and Caucasian prostate cancer models. Parray A, Siddique HR, Kuriger JK, Mishra SK, Rhim JS, Nelson HH, Aburatani H, Konety BR, Koochekpour S, Saleem M.Int. J. Cancer. 2014 Dec 01;135(11):2493-506. doi: 10.1002/ijc.28919 Exploration of liver cancer genomes. Shibata T, Aburatani H.Nat Rev Gastroenterol Hepatol. 2014 Jun;11(6):340-9. doi: 10.1038/nrgastro.2014.6 PRC2 overexpression and PRC2-target gene repression relating to poorer prognosis in small cell lung cancer. Sato T, Kaneda A, Tsuji S, Isagawa T, Yamamoto S, Fujita T, Yamanaka R, Tanaka Y, Nukiwa T, Marquez VE, Ishikawa Y, Ichinose M, Aburatani H.Sci Rep. 2013;3:1911. doi: 10.1038/srep01911 The critical role of cyclin D2 in cell cycle progression and tumorigenicity of glioblastoma stem cells. Koyama-Nasu R, Nasu-Nishimura Y, Todo T, Ino Y, Saito N, Aburatani H, Funato K, Echizen K, Sugano H, Haruta R, Matsui M, Takahashi R, Manabe E, Oda T, Akiyama T.Oncogene. 2013 Aug 15;32(33):3840-5. doi: 10.1038/onc.2012.399 Loss of 5-hydroxymethylcytosine is accompanied with malignant cellular transformation. Kudo Y, Tateishi K, Yamamoto K, Yamamoto S, Asaoka Y, Ijichi H, Nagae G, Yoshida H, Aburatani H, Koike K.Cancer Sci. 2012 Apr;103(4):670-6. doi: 10.1111/j.1349-7006.2012.02213.x Global mapping of cell type-specific open chromatin by FAIRE-seq reveals the regulatory role of the NFI family in adipocyte differentiation. Waki H, Nakamura M, Yamauchi T, Wakabayashi K, Yu J, Hirose-Yotsuya L, Take K, Sun W, Iwabu M, Okada-Iwabu M, Fujita T, Aoyama T, Tsutsumi S, Ueki K, Kodama T, Sakai J, Aburatani H, Kadowaki T.PLoS Genet. 2011 Oct;7(10):e1002311. doi: 10.1371/journal.pgen.1002311 Homozygously deleted gene DACH1 regulates tumor-initiating activity of glioma cells. Watanabe A, Ogiwara H, Ehata S, Mukasa A, Ishikawa S, Maeda D, Ueki K, Ino Y, Todo T, Yamada Y, Fukayama M, Saito N, Miyazono K, Aburatani H.Proc. Natl. Acad. Sci. U.S.A. 2011 Jul 26;108(30):12384-9. doi: 10.1073/pnas.0906930108 Tissue-specific demethylation in CpG-poor promoters during cellular differentiation. Nagae G, Isagawa T, Shiraki N, Fujita T, Yamamoto S, Tsutsumi S, Nonaka A, Yoshiba S, Matsusaka K, Midorikawa Y, Ishikawa S, Soejima H, Fukayama M, Suemori H, Nakatsuji N, Kume S, Aburatani H.Hum. Mol. Genet. 2011 Jul 15;20(14):2710-21. doi: 10.1093/hmg/ddr170 High-resolution characterization of a hepatocellular carcinoma genome. Totoki Y, Tatsuno K, Yamamoto S, Arai Y, Hosoda F, Ishikawa S, Tsutsumi S, Sonoda K, Totsuka H, Shirakihara T, Sakamoto H, Wang L, Ojima H, Shimada K, Kosuge T, Okusaka T, Kato K, Kusuda J, Yoshida T, Aburatani H, Shibata T.Nat. Genet. 2011 May;43(5):464-9. doi: 10.1038/ng.804 Identification of chromosomal aberrations of metastatic potential in colorectal carcinoma. Yamamoto S, Midorikawa Y, Morikawa T, Nishimura Y, Sakamoto H, Ishikawa S, Akagi K, Aburatani H.Genes Chromosomes Cancer. 2010 May;49(5):487-96. doi: 10.1002/gcc.20759 Identification of genes preferentially methylated in hepatitis C virus-related hepatocellular carcinoma. Deng YB, Nagae G, Midorikawa Y, Yagi K, Tsutsumi S, Yamamoto S, Hasegawa K, Kokudo N, Aburatani H, Kaneda A.Cancer Sci. 2010 Jun;101(6):1501-10. doi: 10.1111/j.1349-7006.2010.01549.x Three DNA methylation epigenotypes in human colorectal cancer. Yagi K, Akagi K, Hayashi H, Nagae G, Tsuji S, Isagawa T, Midorikawa Y, Nishimura Y, Sakamoto H, Seto Y, Aburatani H, Kaneda A.Clin. Cancer Res. 2010 Jan 01;16(1):21-33. doi: 10.1158/1078-0432.CCR-09-2006 Population-genetic nature of copy number variations in the human genome. Kato M, Kawaguchi T, Ishikawa S, Umeda T, Nakamichi R, Shapero MH, Jones KW, Nakamura Y, Aburatani H, Tsunoda T.Hum. Mol. Genet. 2010 Mar 01;19(5):761-73. doi: 10.1093/hmg/ddp541 Molecular targets for liver cancer therapy: From screening of target genes to clinical trials. Midorikawa Y, Sugiyama Y, Aburatani H.Hepatol. Res. 2010 Jan 01;40(1):49-60. doi: 10.1111/j.1872-034X.2009.00583.x Allelic imbalances and homozygous deletion on 8p23.2 for stepwise progression of hepatocarcinogenesis. Midorikawa Y, Yamamoto S, Tsuji S, Kamimura N, Ishikawa S, Igarashi H, Makuuchi M, Kokudo N, Sugimura H, Aburatani H.Hepatology. 2009 Feb;49(2):513-22. doi: 10.1002/hep.22698 The S100A8-serum amyloid A3-TLR4 paracrine cascade establishes a pre-metastatic phase. Hiratsuka S, Watanabe A, Sakurai Y, Akashi-Takamura S, Ishibashi S, Miyake K, Shibuya M, Akira S, Aburatani H, Maru Y.Nat. Cell Biol. 2008 Nov;10(11):1349-55. doi: 10.1038/ncb1794 Human homolog of NOTUM, overexpressed in hepatocellular carcinoma, is regulated transcriptionally by beta-catenin/TCF. Torisu Y, Watanabe A, Nonaka A, Midorikawa Y, Makuuchi M, Shimamura T, Sugimura H, Niida A, Akiyama T, Iwanari H, Kodama T, Zeniya M, Aburatani H.Cancer Sci. 2008 Jun;99(6):1139-46. doi: 10.1111/j.1349-7006.2008.00814.x Identification of Toll-like receptor 3 as a potential therapeutic target in clear cell renal cell carcinoma. Morikawa T, Sugiyama A, Kume H, Ota S, Kashima T, Tomita K, Kitamura T, Kodama T, Fukayama M, Aburatani H.Clin. Cancer Res. 2007 Oct 01;13(19):5703-9. doi: 10.1158/1078-0432.CCR-07-0603 Identification of the transforming EML4-ALK fusion gene in non-small-cell lung cancer. Soda M, Choi YL, Enomoto M, Takada S, Yamashita Y, Ishikawa S, Fujiwara S, Watanabe H, Kurashina K, Hatanaka H, Bando M, Ohno S, Ishikawa Y, Aburatani H, Niki T, Sohara Y, Sugiyama Y, Mano H.Nature. 2007 Aug 02;448(7153):561-6. doi: 10.1038/nature05945 Microarray-based analysis for hepatocellular carcinoma: from gene expression profiling to new challenges. Midorikawa Y, Makuuchi M, Tang W, Aburatani H.World J. Gastroenterol. 2007 Mar 14;13(10):1487-92. doi: 10.3748/wjg.v13.i10.1487 Genome-wide detection of human copy number variations using high-density DNA oligonucleotide arrays. Komura D, Shen F, Ishikawa S, Fitch KR, Chen W, Zhang J, Liu G, Ihara S, Nakamura H, Hurles ME, Lee C, Scherer SW, Jones KW, Shapero MH, Huang J, Aburatani H.Genome Res. 2006 Dec;16(12):1575-84. doi: 10.1101/gr.5629106 High-resolution mapping of DNA methylation in human genome using oligonucleotide tiling array. Hayashi H, Nagae G, Tsutsumi S, Kaneshiro K, Kozaki T, Kaneda A, Sugisaki H, Aburatani H.Hum. Genet. 2007 Jan;120(5):701-11. doi: 10.1007/s00439-006-0254-6 Copy number variation: new insights in genome diversity. Freeman JL, Perry GH, Feuk L, Redon R, McCarroll SA, Altshuler DM, Aburatani H, Jones KW, Tyler-Smith C, Hurles ME, Carter NP, Scherer SW, Lee C.Genome Res. 2006 Aug;16(8):949-61. doi: 10.1101/gr.3677206 Identification of ROBO1 as a novel hepatocellular carcinoma antigen and a potential therapeutic and diagnostic target. Ito H, Funahashi S, Yamauchi N, Shibahara J, Midorikawa Y, Kawai S, Kinoshita Y, Watanabe A, Hippo Y, Ohtomo T, Iwanari H, Nakajima A, Makuuchi M, Fukayama M, Hirata Y, Hamakubo T, Kodama T, Tsuchiya M, Aburatani H.Clin. Cancer Res. 2006 Jun 01;12(11 Pt 1):3257-64. doi: 10.1158/1078-0432.CCR-05-2787 The glypican 3 oncofetal protein is a promising diagnostic marker for hepatocellular carcinoma. Yamauchi N, Watanabe A, Hishinuma M, Ohashi K, Midorikawa Y, Morishita Y, Niki T, Shibahara J, Mori M, Makuuchi M, Hippo Y, Kodama T, Iwanari H, Aburatani H, Fukayama M.Mod. Pathol. 2005 Dec;18(12):1591-8. doi: 10.1038/modpathol.3800436 CARAT: a novel method for allelic detection of DNA copy number changes using high density oligonucleotide arrays. Huang J, Wei W, Chen J, Zhang J, Liu G, Di X, Mei R, Ishikawa S, Aburatani H, Jones KW, Shapero MH.BMC Bioinformatics. 2006 Feb 21;7:83. doi: 10.1186/1471-2105-7-83 Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Ge X, Yamamoto S, Tsutsumi S, Midorikawa Y, Ihara S, Wang SM, Aburatani H.Genomics. 2005 Aug;86(2):127-41. doi: 10.1016/j.ygeno.2005.04.008 Allelic dosage analysis with genotyping microarrays. Ishikawa S, Komura D, Tsuji S, Nishimura K, Yamamoto S, Panda B, Huang J, Fukayama M, Jones KW, Aburatani H.Biochem. Biophys. Res. Commun. 2005 Aug 12;333(4):1309-14. doi: 10.1016/j.bbrc.2005.06.040 Overexpression of the aldo-keto reductase family protein AKR1B10 is highly correlated with smokers' non-small cell lung carcinomas. Fukumoto S, Yamauchi N, Moriguchi H, Hippo Y, Watanabe A, Shibahara J, Taniguchi H, Ishikawa S, Ito H, Yamamoto S, Iwanari H, Hironaka M, Ishikawa Y, Niki T, Sohara Y, Kodama T, Nishimura M, Fukayama M, Dosaka-Akita H, Aburatani H.Clin. Cancer Res. 2005 Mar 01;11(5):1776-85. doi: 10.1158/1078-0432.CCR-04-1238 Identification of genes associated with dedifferentiation of hepatocellular carcinoma with expression profiling analysis. Midorikawa Y, Tsutsumi S, Taniguchi H, Ishii M, Kobune Y, Kodama T, Makuuchi M, Aburatani H.Jpn. J. Cancer Res. 2002 Jun;93(6):636-43. doi: 10.1111/j.1349-7006.2002.tb01301.x Global gene expression analysis of gastric cancer by oligonucleotide microarrays. Hippo Y, Taniguchi H, Tsutsumi S, Machida N, Chong JM, Fukayama M, Kodama T, Aburatani H.Cancer Res. 2002 Jan 01;62(1):233-40. Direct comparison of GeneChip and SAGE on the quantitative accuracy in transcript profiling analysis. Ishii M, Hashimoto S, Tsutsumi S, Wada Y, Matsushima K, Kodama T, Aburatani H.Genomics. 2000 Sep 01;68(2):136-43. doi: 10.1006/geno.2000.6284