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Kaoru Uchimaru / Professor / Division of Biosciences
Department of Computational Biology and Medical Sciences / / HTLV-1 infection, Adult T-cell leukemia
http://uchimaru.umin.jp/

Career Summary
1986: Graduated from Faculty of Medicine (University of Tokyo)
1986: Resident of Internal Medicine, the University of Tokyo Hospital, Branch Hospital of the University of Tokyo, Ibaraki Prefectural Hospital
1992: Research Associate (the 4th Department of Internal Medicine, the University of Tokyo)
1987: Lecturer (the 3rd Department of Internal Medicine, Teikyo University)
2000: Assistant Professor (Department of Internal Medicine, Research Hospital, the Institute of Medical Science, the University of Tokyo (IMSUT))
2002: Lecturer (Department of Internal Medicine, Research Hospital, IMSUT)
2005: Associate Professor (Department of Internal Medicine, Research Hospital, IMSUT)
2016: Professor (Department of Computational Biology and Medical Science, GSFS)
Educational Activities
Graduate school: Internal Medicine, Human Retrovirology
Research Activities
Regulation of Hematopoiesis through activin A production by bone marrow stromal cells (refs. 1, 2)
Cell cycle regulation at the terminal differentiation of hematopoietic cells
Cyclin D expression in hematopoietic malignancies
(refs. 3-6)
Cancer immunotherapy using dendritic cells
(refs. 7-9)
Epidemiology, Political science of HTLV-1 infection (ref. 10)
Phenotypical analysis of HTLV-1 infected cells through oncogenic process to ATL (refs. 11-14)
Analysis of molecular mechanism of ATL development (ref. 15, 16)

Clinical research on ATL (refs. 17, 18)
Literature
1) Takahashi S., Uchimaru K., Harigaya K., Asano S., and Yamashita T. Tumor necrosis factor and interleukin-1 induce activin A gene expression in a human bone marrow stromal cell line. Biochem. Biophys. Res. Commun., 188:310-317 (1992)
2) Uchimaru K., Motokura T., Takahashi S., Sakurai T., Asano S., and Yamashita T. Bone marrow stromal cells produce and respond to activin A: interactions with basic fibroblast growth factor and platelet-derived growth factor. Exp. Heamtol., 23:613-618 (1995)
3) Uchimaru K., Taniguchi T., Yoshikawa M., Fujinuma H., Fujita T., and Motokura T. Growth arrest associated with 12-o-tetradecanoylphorbol-13-acetate-induced hematopoietic differentiation with a defective retinoblastoma tumor suppressor-mediated pathway. Leuk. Res., 22:413-20 (1998)
4) Kobayashi H., Saito H., Kitano K., Kiyosawa K., Gaun S., Aoki K., Narita A., Watanabe M., Uchimaru K., and Motokura T. Overexpression of the PRAD1 oncogene in a patient with multiple myeloma and t(11;14)(q13;q32). Acta Hematol., 94:199-203 (1995)
5) Kobayashi H., Kitano K., Saito H., Aoki K., Narita A., Terada N., Sonoyama M., Uchimaru K., Machii T., and Motokura T. Overexpression of the PRAD1 oncogene in a patient with prolymphocytic leukemia with t(11;14)(q13;q32). Cancer Genet. Cytogenet., 84:69-72 (1995)
6) Uchimaru K., Tanguchi T., Yoshikawa M., Asano S., Arnold A., Fujita T., and Motokura T. Detection of cyclin D1(bcl-1, PRAD1) overexpression by a simple competitive reverse transcription-polymerase chain reaction assay in t(11;14)(q13;q32)-bearing B-cell malignancies and/or mantle cell lymphoma. Blood, 89:965-974 (1997)
7) Nagayama H., Sato K., Morishita M., Uchimaru K., Oyaizu N., Inazawa T., Yamasaki T., Enomoto M., Nakaoka T., Nakamura T., Maekawa T., Yamamoto A., Shimada S., Saida T., Kawakami Y., Asano S., Tani K., Takahashi T.A., and Yamashita N. Results of phase I clinical study using autologous tumor-lysate pulsed monocyte-derived mature dendritic cell vaccinations for stage IV malignant melanoma patients combined with low dose interleukin-2. Melanoma Research 13: 1-10 (2003)
8) Morishita M., Uchimaru K., Sato K., Yamashita S., Kanematsu T., and Yamashita N. Thyroglobulin-pulsed human monocyte-derived dendritic cells induce CD4+T cell activation. Int. J. Mol. Med., 13: 33-39 (2004)
9) Kuwabara K., Nishishita T., Morishita M., Oyaizu N., Yamashita S., Kanematsu T., Obara T., Mimura Y., Inoue Y., Kaminishi M., Kaga K., Amino N., Kitaoka M., Ito K., Miyauchi A., Noguchi S., Uchimaru K., Akagawa E., Watanabe N., Takahashi T.A., Sato K., Inazawa T., Nakaoka T., and Yamashita N. Results of a phase I clinical study using dendritic cell vaccinations for thyroid cancer. Thyroid. 17: 53-8 (2007)
10) Uchimaru K., Nakamura Y., Tojo A., Watanabe T., and Yamaguchi K. Factors predisposing to HTLV-1 infection in residents of the greater Tokyo Area. Int J Hematol. 88: 565-570, 2008.
11) Yamin Tian, Seiichro Kobayashi, Nobuhiro Ohno, Masamichi Isobe, Mayuko Tsuda, Yuji Zaike, Nobukazu Watanabe, Kenzaburo Tani, Arinobu Tojo, and Kaoru Uchimaru. Leukemic T cells are specifically enriched in a unique CD3dimCD7low subpopulation of CD4+ T cells in acute-type adult T-cell leukemia. Cancer Sci. 2011 102(3): 569-577.
12) Kobayashi S., Tian Y., Ohno N., Yuji K., Ishigaki T., Isobe M., Ohfuchi-Tsuda M., Oyaizu N., Watanabe E., Watanabe N., Tani K., Tojo A., and Uchimaru K. The CD3 versus CD7 plot in multicolor flow cytometry reflects progression of disease stage in patients infected with HTLV-I. PLoS One 8: e53728, doi:10.1371/journal.pone.0053728, 2013.
13) Kobayashi S., Nakano K., Watanabe E., Ishigaki T., Ohno N., Yuji K., Oyaizu N., Asanuma S., Yamagishi M., Yamochi T., Watanabe N., Tojo A., Watanabe T., and Uchimaru K. CADM1 expression and stepwise downregulation of CD7 are closely associated with clonal expansion of HTLV-I-infected cells in adult t-cell leukemia/lymphoma. Clin Cancer Res. 2014 Jun 1;20(11):2851-61.
14) Kobayashi S., Watanabe E., Ishigaki T., Ohno N., Yuji K., Nakano K., Yamochi T., Watanabe N., Tojo A., Watanabe T., and Uchimaru K. Advanced human T-cell leukemia virus type 1 carriers and early-stage indolent adult T-cell leukemia-lymphoma are indistinguishable based on CADM1 positivity in flow cytometry. Cancer Sci. 2015 May; 106(5):598-603.
15) Makoto Yamagishi, Kazumi Nakano, Ariko Miyake, Tadanori Yamochi, Yayoi Kagami, Akihisa Tsutsumi, Yuka Matsuda, Aiko Sato-Otsubo, Satsuki Muto, Atae Utsunomiya, Kazunari Yamaguchi, Kaoru Uchimaru, Seishi Ogawa, and Toshiki Watanabe. Polycomb-Mediated Loss of miR-31 Activates NIK-dependent NF-k B Pathway in Adult T-cell Leukemia and Other Cancers. Cancer cell. 2012 21(1):121-135
16) Fujikawa D., Nakagawa S., Hori M., Kurokawa N., Soejima A., Nakano K., Yamochi T., Nakashima M., Kobayashi S., Tanaka Y., Iwanaga M., Utsunomiya A., Uchimaru K., Yamagishi M., and Watanabe T. Polycomb-dependent epigenetic landscape in adult T-cell leukemia. Blood. 2016 Apr 7;127(14):1790-802.
17) Fuji S., Inoue Y., Utsunomiya A., Moriuchi Y., Uchimaru K., Choi I., Otsuka E., Henzan H., Kato K., Tomoyose T., Yamamoto H., Kurosawa S., Matsuoka K.I., Yamaguchi T., and Fukuda T. Pretransplantation Anti-CCR4 Antibody Mogamulizumab Against Adult T-Cell Leukemia/Lymphoma Is Associated With Significantly Increased Risks of Severe and Corticosteroid-Refractory Graft-Versus-Host Disease, Nonrelapse Mortality, and Overall Mortality. J Clin Oncol. 2016 Oct 1;34(28):3426-33.
18) Fuji S., Yamaguchi T., Inoue Y., Utsunomiya A., Moriuchi Y., Uchimaru K., Owatari S., Miyagi T., Taguchi J., Choi I., Otsuka E., Nakachi S., Yamamoto H., Kurosawa S., Tobinai K., and Fukuda T. Development of a modified prognostic index of patients with aggressive adult T-cell leukemia-lymphoma aged 70 years or younger: a possible risk-adapted management strategies including allogeneic transplantation. Haematologica. 2017 [E-pub ahead of print]
Other Activities
The Japanese Society of Internal Medicine
The Japanese Society of Hematology
The Japanese Society of HTLV-1 and Related Diseases
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Future Plan
Our ultimate goal is to develop new therapies for ATL, HAM and other related diseases of HTLV-1, the most intractable diseases. For these purposes, we are now analyzing the mechanism of development of ATL and HTLV-1 related diseases using multi-omics technologies. We also will be one of the core centers of ATL therapies and political sciences of HTLV-1 infection.
Messages to Students
I hope you young scientists will join us in our mission to develop new therapies of ATL and future medicine. Letfs enjoy medical science!
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