Tsuyoshi OSAWA
LABORATORY
https://www.onc.rcast.u-tokyo.ac.jp/ja/PROFILE
2001- BSc. Medical Biochemistry, King's College London
2010- Ph.D., Cancer Institute, University College London
2006- Researcher, Department of Genetics, Institute of Medical Science, The University of Tokyo (UTokyo)
2007- Assistant Professor, Department of Oncology, Graduate School of Medicine and Dentistry, Tokyo Medical and Dental University
2011- Research Associate, RCAST, UTokyo
2018- Project Associate Professor, RCAST, UTokyo
FIELD OF INTEREST
Cancer research is entering a new era. We aimed to create novel cancer treatments through “Nutriomics” approach,the integration of nutrition and omics data. Carbohydrates, lipids and amino acids were independently considered in cancer. However, recent researches in cancer metabolism have been dramatically improved our metabolic knowledge due to latest understanding of cancer metabolism. Indeed, carbohydrates, lipids and amino acids are inter-connected in the metabolic pathways, through the several key metabolic molecules such as acetyl-CoA and ketone body intermediates partly under epigenetic regulation. Our group reported that hypoxia, nutrient starvation, acidic pH may induce tumor aggressiveness by epigenetic regulation in cancer cells. We found that multi-layered omics changes including epigenetic and metabolic changes influence cancer progression, that can be utilizes for the development of novel therapies by integration of genome, epigenome, transcriptome, proteome, metabolome analysis. Our research objectives:
1. To identify novel onco-metabolites (cancer associated metabolites) for the treatment of cancer.
2. To understand the mechanism of cancer adaptation in carbohydrate/lipids/amino acids deficiency and apply it to therapy.
3. Latest understanding of “nutriomics” for treatment of cancer. We challenge to develop therapeutics for metastasis and recurrent advanced cancer through the viewpoint of integrative “multi-layered omics” approach.
PUBLICATION
- Dynamically and epigenetically coordinated GATA/ETS/SOX transcription factor expression is indispensable for endothelial cell differentiation. Kanki Y, Nakaki R, Shimamura T, Matsunaga T, Yamamizu K, Katayama S, Suehiro JI, Osawa T, Aburatani H, Kodama T, Wada Y, Yamashita JK, Minami T.Nucleic Acids Res. 2017 05 05;45(8):4344-4358. doi: 10.1093/nar/gkx159 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 A major role for RCAN1 in atherosclerosis progression. Méndez-Barbero N, Esteban V, Villahoz S, Escolano A, Urso K, Alfranca A, Rodríguez C, Sánchez SA, Osawa T, Andrés V, Martínez-González J, Minami T, Redondo JM, Campanero MR.EMBO Mol Med. 2013 Dec;5(12):1901-17. doi: 10.1002/emmm.201302842 BMP4/Thrombospondin-1 loop paracrinically inhibits tumor angiogenesis and suppresses the growth of solid tumors. Tsuchida R, Osawa T, Wang F, Nishii R, Das B, Tsuchida S, Muramatsu M, Takahashi T, Inoue T, Wada Y, Minami T, Yuasa Y, Shibuya M.Oncogene. 2014 Jul 17;33(29):3803-11. doi: 10.1038/onc.2013.358 The calcineurin-NFAT-angiopoietin-2 signaling axis in lung endothelium is critical for the establishment of lung metastases. Minami T, Jiang S, Schadler K, Suehiro J, Osawa T, Oike Y, Miura M, Naito M, Kodama T, Ryeom S.Cell Rep. 2013 Aug 29;4(4):709-23. doi: 10.1016/j.celrep.2013.07.021 Targeting cancer cells resistant to hypoxia and nutrient starvation to improve anti-angiogeneic therapy. Osawa T, Shibuya M.Cell Cycle. 2013 Aug 15;12(16):2519-20. doi: 10.4161/cc.25729 Inhibition of histone demethylase JMJD1A improves anti-angiogenic therapy and reduces tumor-associated macrophages. Osawa T, Tsuchida R, Muramatsu M, Shimamura T, Wang F, Suehiro J, Kanki Y, Wada Y, Yuasa Y, Aburatani H, Miyano S, Minami T, Kodama T, Shibuya M.Cancer Res. 2013 May 15;73(10):3019-28. doi: 10.1158/0008-5472.CAN-12-3231 Alternative splicing of CD44 mRNA by ESRP1 enhances lung colonization of metastatic cancer cell. Yae T, Tsuchihashi K, Ishimoto T, Motohara T, Yoshikawa M, Yoshida GJ, Wada T, Masuko T, Mogushi K, Tanaka H, Osawa T, Kanki Y, Minami T, Aburatani H, Ohmura M, Kubo A, Suematsu M, Takahashi K, Saya H, Nagano O.Nat Commun. 2012 Jun 06;3:883. doi: 10.1038/ncomms1892 Increased expression of histone demethylase JHDM1D under nutrient starvation suppresses tumor growth via down-regulating angiogenesis. Osawa T, Muramatsu M, Wang F, Tsuchida R, Kodama T, Minami T, Shibuya M.Proc. Natl. Acad. Sci. U.S.A. 2011 Dec 20;108(51):20725-9. doi: 10.1073/pnas.1108462109 Downregulation of receptor for activated C-kinase 1 (RACK1) suppresses tumor growth by inhibiting tumor cell proliferation and tumor-associated angiogenesis. Wang F, Osawa T, Tsuchida R, Yuasa Y, Shibuya M.Cancer Sci. 2011 Nov;102(11):2007-13. doi: 10.1111/j.1349-7006.2011.02065.x Mechanism of cell death resulting from DNA interstrand cross-linking in mammalian cells. Osawa T, Davies D, Hartley JA.Cell Death Dis. 2011 Aug 04;2:e187. doi: 10.1038/cddis.2011.70 Human glioblastoma cells exposed to long-term hypoxia and nutrient starvation stimulated induction of secondary T-cell leukemia in mice. Osawa T, Tsuchida R, Muramatsu M, Yuasa Y, Shibuya M.Blood Cancer J. 2011 Feb;1(2):e6. doi: 10.1038/bcj.2011.5 RACK1 regulates VEGF/Flt1-mediated cell migration via activation of a PI3K/Akt pathway. Wang F, Yamauchi M, Muramatsu M, Osawa T, Tsuchida R, Shibuya M.J. Biol. Chem. 2011 Mar 18;286(11):9097-106. doi: 10.1074/jbc.M110.165605 Vascular endothelial growth factor receptor-1 signaling promotes mobilization of macrophage lineage cells from bone marrow and stimulates solid tumor growth. Muramatsu M, Yamamoto S, Osawa T, Shibuya M.Cancer Res. 2010 Oct 15;70(20):8211-21. doi: 10.1158/0008-5472.CAN-10-0202 Quinone oxidoreductase-2-mediated prodrug cancer therapy. Middleton MR, Knox R, Cattell E, Oppermann U, Midgley R, Ali R, Auton T, Agarwal R, Anderson D, Sarker D, Judson I, Osawa T, Spanswick VJ, Davies S, Hartley JA, Kerr DJ.Sci Transl Med. 2010 Jul 14;2(40):40ra50. doi: 10.1126/scitranslmed.3000615 Hypoxia and low-nutrition double stress induces aggressiveness in a murine model of melanoma. Osawa T, Muramatsu M, Watanabe M, Shibuya M.Cancer Sci. 2009 May;100(5):844-51. doi: 10.1111/j.1349-7006.2009.01105.x