今月の研究者

高木 伸介

高木 伸介

1) キャリア
2002年に岡山大学を卒業後、研修医として虎の門病院でご指導頂き、2007年から血液内科医員に採用頂きました。2009年に千葉大学大学院に入学し、横浜の理化学研究所(理研)で研究に従事させて頂きました。理研では石川文彦博士のご指導のもと、ヒト化マウス(免疫不全マウスにヒト造血を再構築したもの)を用いて白血病幹細胞や骨髄微小環境の研究を行いました。2012年に大学院を卒業し、2013年から分院、2014年から本院の血液内科医員として再び虎の門病院で血液内科診療を行う機会を与えて頂いています。

2) 研究分野
2003年から赴任した谷口修一部長をはじめとした多くの先輩方のご尽力により臍帯血移植が普及し、その恩恵を受ける重症患者さんたちを研修医として眼の当たりにしました。その時に受けた衝撃が純粋に単純に現在の私の血液内科診療に対する情熱を灯し続けています。現在は、臍帯血移植やその後の合併症に加えて造血器疾患の発症から治癒までを幅広く、臨床医学と医科学の両方の視点から研究対象としています。また、共同研究を通して理研とも継続的に繋がっており、理研と虎の門病院、そして当研究所が組むユニークかつ強力なタッグが造血器疾患の治療に大きな風穴を開ける日もそう遠くないと信じています。

造血器疾患
・白血病幹細胞が急性骨髄性白血病の治療に与える影響について
・原発性および二次性骨髄線維症に対する同種造血細胞移植について
・急性混合性白血病に対する同種造血細胞移植について
・慢性骨髄性白血病に対する臍帯血移植について
・急性骨髄性白血病に対する新規標的療法の開発について(理研との共同研究)

移植療法
・臍帯血に含まれるCD34 細胞数と臍帯血移植後の生着について
・高齢者に対する新たな臍帯血移植の前処置の開発について
・臍帯血移植後の血球貪食症候群について
・臍帯血移植後の早期免疫合併症とそれらの至適制御方法の開発について
・同種造血細胞移植後の血流感染について
・同種造血細胞移植後の類洞閉塞症候群と凝固異常について
・同種造血細胞移植後の末梢神経合併症について
・同種造血細胞移植後の抗真菌薬の体内動態について

3) 今後の抱負・アピール
様々な領域に課題を見出し同時進行で研究を進めています。これら一つ一つは虎の門病院での臨床と理研での研究における私自身の実体験に基づいた疑問や苦悩であり、克服すべき課題ばかりです。志を同じくする仲間たちと共に新しい知見を見出し、世界に発信していきたいと思います。研究から臨床へ、臨床から研究へ、両輪の架け橋になりながら、それらがそれぞれに大きく実り、力強い進歩が患者さんの元へ届くことで社会に還元できるよう今後も精進致します。

発表・論文

筆頭著者

1. Takagi S, Masuoka K, Uchida N, Kurokawa M, Nakamae H, Imada K, Iwato K, Ichinohe T, Atsuta Y, Takami A, Yano S. Allogeneic Hematopoietic Cell Transplantation for Leukemic Transformation Preceded by Philadelphia Chromosome-Negative Myeloproliferative Neoplasms: A Nationwide Survey by the Adult Acute Myeloid Leukemia Working Group of the Japan Society for Hematopoietic Cell Transplantation. Biol Blood Marrow Transplant. 2016 Dec;22(12):2208-2213.

2. Takagi S, Araoka H, Uchida N, Uchida Y, Kaji D, Ota H, Nishida A, Ishiwata K, Tsuji M, Yamamoto H, Ito T, Matsuno N, Yamamoto G, Asano-Mori Y, Hayashi M, Izutsu K, Masuoka K, Wake A, Makino S, Yoneyama A, Taniguchi S. A prospective feasibility study of primary prophylaxis against invasive fungal disease with voriconazole following umbilical cord blood transplantation with fludarabine-based conditioning. Int J Hematol. 2014;99(5):652-8.

3. Takagi S, Saito Y, Hijikata A, Tanaka S, Watanabe T, Hasegawa T, Mochizuki S, Kunisawa J, Kiyono H, Koseki H, Ohara O, Saito T, Taniguchi S, Shultz LD, Ishikawa F. Membrane-bound human SCF/KL promotes in vivo human hematopoietic engraftment and myeloid differentiation. Blood. 2012 Mar 22;119(12):2768-77.

4. Takagi S, Ota Y, Uchida N, Takahashi K, Ishiwata K, Tsuji M, Yamamoto H, Asano-Mori Y, Matsuno N, Masuoka K, Wake A, Miyakoshi S, Ohashi K, Taniguchi S. Successful engraftment after reduced-intensity umbilical cord blood transplantation for myelofibrosis. Blood. 2010 Jul 29;116(4):649-52.

5. Takagi S, Masuoka K, Uchida N, Ishiwata K, Araoka H, Tsuji M, Yamamoto H, Kato D, Matsuhashi Y, Kusumi E, Ota Y, Seo S, Matsumura T, Matsuno N, Wake A, Miyakoshi S, Makino S, Ohashi K, Yoneyama A, Taniguchi S. High incidence of haemophagocytic syndrome following umbilical cord blood transplantation for adults. Br J Haematol. 2009 Nov;147(4):543-53.

共同著者

2018年

6. Fujimoto H, Saito Y, Ohuchida K, Kawakami E, Fujiki S, Watanabe T, Ono R, Kaneko A, Takagi S, Najima Y, Hijikata A, Cui L, Ueki T, Oda Y, Hori S, Ohara O, Nakamura M, Saito T, Ishikawa F. Deregulated Mucosal Immune Surveillance through Gut-Associated Regulatory T Cells and PD-1+ T Cells in Human Colorectal Cancer. J Immunol. 2018 May 1;200(9):3291-3303.

7. Kimura M, Araoka H, Yamamoto H, Nakamura S, Nagi M, Yamagoe S, Miyazaki Y, Ogura S, Mitsuki T, Yuasa M, Kaji D, Kageyama K, Nishida A, Taya Y, Shimazu H, Ishiwata K, Takagi S, Yamamoto G, Asano-Mori Y, Uchida N, Wake A, Taniguchi S, Yoneyama A. Micafungin Breakthrough Fungemia in Patients with Hematological Disorders. Antimicrob Agents Chemother. 2018 Apr 26;62(5). pii: e02183-17.

2017年

8. Saito Y, Mochizuki Y, Ogahara I, Watanabe T, Hogdal L, Takagi S, Sato K, Kaneko A, Kajita H, Uchida N, Fukami T, Shultz LD, Taniguchi S, Ohara O, Letai AG, Ishikawa F. Overcoming mutational complexity in acute myeloid leukemia by inhibition of critical pathways. Sci Transl Med. 2017 Oct 25;9(413). pii: eaao1214.

9. Ota H, Yamamoto H, Kimura M, Araoka H, Fujii T, Umeyama T, Ohno H, Miyazaki Y, Kaji D, Taya Y, Nishida A, Ishiwata K, Tsuji M, Takagi S, Asano-Mori Y, Yamamoto G, Uchida N, Izutsu K, Masuoka K, Wake A, Yoneyama A, Makino S, Taniguchi S. Successful Treatment of Pulmonary Mucormycosis Caused by Cunninghamella bertholletiae with High-Dose Liposomal Amphotericin B (10 mg/kg/day) Followed by a Lobectomy in Cord Blood Transplant Recipients. Mycopathologia. 2017 Oct;182(9-10):847-853.

10. Kimura M, Araoka H, Yamamoto H, Asano-Mori Y, Nakamura S, Yamagoe S, Ohno H, Miyazaki Y, Abe M, Yuasa M, Kaji D, Kageyama K, Nishida A, Ishiwata K, Takagi S, Yamamoto G, Uchida N, Izutsu K, Wake A, Taniguchi S, Yoneyama A. Clinical and Microbiological Characteristics of Breakthrough Candidemia in Allogeneic Hematopoietic Stem Cell Transplant Recipients in a Japanese Hospital. Antimicrob Agents Chemother. 2017 Mar 24;61(4). pii: e01791-16.

2016年

11. Yamamoto H, Uchida N, Yuasa M, Kageyama K, Ota H, Kaji D, Nishida A, Ishiwata K, Takagi S, Tsuji M, Asano-Mori Y, Yamamoto G, Izutsu K, Masuoka K, Wake A, Yoneyama A, Makino S, Taniguchi S. A Novel Reduced-Toxicity Myeloablative Conditioning Regimen Using Full-Dose Busulfan, Fludarabine, and Melphalan for Single Cord Blood Transplantation Provides Durable Engraftment and Remission in Nonremission Myeloid Malignancies. Biol Blood Marrow Transplant. 2016 Oct;22(10):1844-1850.

12. Kimura M, Araoka H, Yoshida A, Yamamoto H, Abe M, Okamoto Y, Yuasa M, Kaji D, Kageyama K, Nishida A, Ishiwata K, Takagi S, Yamamoto G, Asano-Mori Y, Uchida N, Hishinuma A, Izutsu K, Wake A, Taniguchi S, Yoneyama A. Breakthrough viridans streptococcal bacteremia in allogeneic hematopoietic stem cell transplant recipients receiving levofloxacin prophylaxis in a Japanese hospital. BMC Infect Dis. 2016 Aug 5;16:372.

2015年

13. Yamamoto H, Uchida N, Uchida Y, Nishida A, Ota H, Kageyama K, Nasu I, Wada S, Kaji D, Ishiwata K, Takagi S, Tsuji M, Asano-Mori Y, Matsuno N, Yamamoto G, Masuoka K, Izutsu K, Wake A, Yoneyama A, Makino S, Ito T, Hayashi M, Taniguchi S. Oral beclomethasone dipropionate as an initial treatment for stages 1-2 gastrointestinal tract acute graft-versus-host disease following unrelated cord blood transplantation. Ann Hematol. 2015 Dec;94(12):2073-5.

14. Yamamoto H, Uchida N, Matsuno N, Kon A, Nishida A, Ota H, Ikebe T, Nakano N, Ishiwata K, Araoka H, Takagi S, Tsuji M, Asano-Mori Y, Yamamoto G, Izutsu K, Masuoka K, Wake A, Yoneyama A, Makino S, Taniguchi S. I.v. BU/fludarabine plus melphalan or TBI in unrelated cord blood transplantation for high-risk hematological diseases. Bone Marrow Transplant. 2015 Apr;50(4):607-9.

2014年

15. Yamamoto H, Uchida N, Matsuno N, Ota H, Kageyama K, Wada S, Kaji D, Nishida A, Ishiwata K, Takagi S, Tsuji M, Asano-Mori Y, Yamamoto G, Izutsu K, Masuoka K, Wake A, Yoneyama A, Makino S, Taniguchi S. Anti-HLA antibodies other than against HLA-A, -B, -DRB1 adversely affect engraftment and nonrelapse mortality in HLA-mismatched single cord blood transplantation: possible implications of unrecognized donor-specific antibodies. Biol Blood Marrow Transplant. 2014 Oct;20(10):1634-40.

16. Hosokawa K, Takami A, Tsuji M, Araoka H, Ishiwata K, Takagi S, Yamamoto H, Asano-Mori Y, Matsuno N, Uchida N, Masuoka K, Wake A, Makino S, Yoneyama A, Nakao S, Taniguchi S. Relative incidences and outcomes of Clostridium difficile infection following transplantation of unrelated cord blood, unrelated bone marrow, and related peripheral blood in adult patients: a single institute study. Transpl Infect Dis. 2014 Jun;16(3):412-20.

2013年

17. Saito Y, Yuki H, Kuratani M, Hashizume Y, Takagi S, Honma T, Tanaka A, Shirouzu M, Mikuni J, Handa N, Ogahara I, Sone A, Najima Y, Tomabechi Y, Wakiyama M, Uchida N, Tomizawa-Murasawa M, Kaneko A, Tanaka S, Suzuki N, Kajita H, Aoki Y, Ohara O, Shultz LD, Fukami T, Goto T, Taniguchi S, Yokoyama S, Ishikawa F. A pyrrolo-pyrimidine derivative targets human primary AML stem cells in vivo. Sci Transl Med. 2013 Apr 17;5(181):181ra52.

2012年

18. Suzuki S, Iwamoto M, Saito Y, Fuchimoto D, Sembon S, Suzuki M, Mikawa S, Hashimoto M, Aoki Y, Najima Y, Takagi S, Suzuki N, Suzuki E, Kubo M, Mimuro J, Kashiwakura Y, Madoiwa S, Sakata Y, Perry AC, Ishikawa F, Onishi A. Il2rg gene-targeted severe combined immunodeficiency pigs. Cell Stem Cell. 2012 Jun 14;10(6):753-8.

19. Ito T, Uchida Y, Takagi S, Uchida N, Taniguchi S, Hayashi M. [A case report of severe hypo-phosphatemia due to paraneoplastic syndrome followed by severe hyper-phosphatemia due to tumor lysis syndrome after CHOP chemotherapy]. Gan To Kagaku Ryoho. 2012 Feb;39(2):325-8.

2011年

20. Uchida N, Wake A, Nakano N, Ishiwata K, Takagi S, Tsuji M, Yamamoto H, Kato D, Matsuno N, Masuoka K, Araoka H, Asano-Mori Y, Izutsu K, Makino S, Yoneyama A, Taniguchi S. Mycophenolate and tacrolimus for graft-versus-host disease prophylaxis for elderly after cord blood transplantation: a matched pair comparison with tacrolimus alone. Transplantation. 2011 Aug 15;92(3):366-71.

21. Masuoka K, Uchida N, Ishiwata K, Takagi S, Tsuji M, Yamamoto H, Seo S, Matsuno N, Wake A, Makino S, Yoneyama A, Taniguchi S. What is the upper age limit for performing allo-SCT? Cord blood transplantation for an 82-year-old patient with AML. Bone Marrow Transplant. 2011 Apr;46(4):619-20.

22. Yamamoto H, Kato D, Uchida N, Ishiwata K, Araoka H, Takagi S, Nakano N, Tsuji M, Asano-Mori Y, Matsuno N, Masuoka K, Izutsu K, Wake A, Yoneyama A, Makino S, Taniguchi S. Successful sustained engraftment after reduced-intensity umbilical cord blood transplantation for adult patients with severe aplastic anemia. Blood. 2011 Mar 17;117(11):3240-2.

23. Nasu I, Ito T, Minowa M, Furusawa M, Okuno Y, Uchida Y, Ishiwata K, Nakano K, Tsuji M, Takagi S, Yamamoto H, Matsuno N, Mori Y, Uchida N, Masuoka K, Wake A, Makino S, Miyakoshi S, Taniguchi S, Hayashi M. [Optimal therapeutic concentration of tacrolimus in adult patients undergoing reduced-intensity cord blood transplantation]. Gan To Kagaku Ryoho. 2011;38(2):249-53.

2010年

24. Araoka H, Baba M, Takagi S, Matsuno N, Ishiwata K, Nakano N, Tsuji M, Yamamoto H, Seo S, Asano-Mori Y, Uchida N, Masuoka K, Wake A, Taniguchi S, Yoneyama A. Monobactam and aminoglycoside combination therapy against metallo-beta-lactamase-producing multidrug-resistant Pseudomonas aeruginosa screened using a 'break-point checkerboard plate'. Scand J Infect Dis. 2010 Mar;42(3):231-3.

25. Saito Y, Uchida N, Tanaka S, Suzuki N, Tomizawa-Murasawa M, Sone A, Najima Y, Takagi S, Aoki Y, Wake A, Taniguchi S, Shultz LD, Ishikawa F. Induction of cell cycle entry eliminates human leukemia stem cells in a mouse model of AML. Nat Biotechnol. 2010 Mar;28(3):275-80.

26. Saito Y, Kitamura H, Hijikata A, Tomizawa-Murasawa M, Tanaka S, Takagi S, Uchida N, Suzuki N, Sone A, Najima Y, Ozawa H, Wake A, Taniguchi S, Shultz LD, Ohara O, Ishikawa F. Identification of therapeutic targets for quiescent, chemotherapy-resistant human leukemia stem cells. Sci Transl Med. 2010 Feb 3;2(17):17ra9.

27. Ito T, Watanabe K, Nasu I, Ino K, Minowa M, Furusawa M, Okuno Y, Uchida Y, Miyazaki Y, Tamura H, Hasebe S, Takagi S, Yamamoto H, Matsuno N, Uchida N, Masuoka K, Wake A, Makino S, Taniguchi S, Hayashi M. [Analysis of blood concentrations following oral administration of beclomethasone dipropionate for gut GVHD]. Gan To Kagaku Ryoho. 2010 Feb;37(2):267-70.

2009年

28. Yamamoto H, Uchida N, Ishiwata K, Araoka H, Takagi S, Tsuji M, Kato D, Matsuhashi Y, Seo S, Matsuno N, Masuoka K, Wake A, Yoneyama A, Makino S, Taniguchi S. Possible graft-versus-host disease involving the central nervous system soon after cord bloodtransplantation. Am J Hematol. 2009 Nov;84(11):764-6.

29. Matsuno N, Wake A, Uchida N, Ishiwata K, Araoka H, Takagi S, Tsuji M, Yamamoto H, Kato D, Matsuhashi Y, Seo S, Masuoka K, Miyakoshi S, Makino S, Yoneyama A, Kanda Y, Taniguchi S. Impact of HLA disparity in the graft-versus-host direction on engraftment in adult patients receiving reduced-intensity cord blood transplantation. Blood. 2009 Aug 20;114(8):1689-95.

2008年

30. Uchida N, Wake A, Takagi S, Yamamoto H, Kato D, Matsuhashi Y, Matsumura T, Seo S, Matsuno N, Masuoka K, Kusumi E, Yuji K, Miyakoshi S, Matsuzaki M, Yoneyama A, Taniguchi S. Umbilical cord blood transplantation after reduced-intensity conditioning for elderly patients with hematologic diseases. Biol Blood Marrow Transplant. 2008 May;14(5):583-90.

31. Araoka H, Baba M, Tatsushima K, Takagi S, Matsuno N, Wake A, Taniguchi S, Yoneyama A. [Case of sepsis caused by multidrug-resistant neutropenic-phase Pseudomonas aeruginosa treated successfully with antibiotic combination therapy]. Kansenshogaku Zasshi. 2008 Sep;82(5):466-70.

2007年

32. Miyakoshi S, Kami M, Tanimoto T, Yamaguchi T, Narimatsu H, Kusumi E, Matsumura T, Takagi S, Kato D, Kishi Y, Murashige N, Yuji K, Uchida N, Masuoka K, Wake A, Taniguchi S. Tacrolimus as prophylaxis for acute graft-versus-host disease in reduced intensity cord blood transplantation for adult patients with advanced hematologic diseases. Transplantation. 2007 Aug 15;84(3):316-22.

2006年

33. Kusumi E, Yuji K, Kishi A, Murashige N, Takagi S, Matsumura T, Tanaka Y, Miyakoshi S, Kami M, Taniguchi S. Molluscum contagiosum infection after reduced-intensity cord blood transplantation. Bone Marrow Transplant. 2006 Aug;38(4):313-4. Epub 2006 Jun 19.

2005年

34. Narimatsu H, Wake A, Miura Y, Tanaka H, Matsumura T, Takagi S, Kato D, Myojo T, Kusumi E, Masuoka K, Miyakoshi S, Morinaga S, Saji H, Ichinohe T, Taniguchi S. Successful engraftment in crossmatch-positive HLA-mismatched peripheral blood stem cell transplantation after depletion of antidonor cytotoxic HLA antibodies with rituximab and donor platelet infusion. Bone Marrow Transplant. 2005 Sep;36(6):555-6.

35. Narimatsu H, Matsumura T, Kami M, Miyakoshi S, Kusumi E, Takagi S, Miura Y, Kato D, Inokuchi C, Myojo T, Kishi Y, Murashige N, Yuji K, Masuoka K, Yoneyama A, Wake A, Morinaga S, Kanda Y, Taniguchi S. Bloodstream infection after umbilical cord blood transplantation using reduced-intensity stem cell transplantation for adult patients. Biol Blood Marrow Transplant. 2005 Jun;11(6):429-36.

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