Research Assistant Professor, Department of Investigative Medicine
Biosketch
Michihiro Kobayashi, MD, PhD received his degrees from the Mie University School of Medicine in Japan, with extensive training in Hematology/ Oncology. Dr. Kobayashi has broad and extensive experience in clinical Hematology/ Oncology and general Pediatrics. After initial training, he worked at the National Cancer Center Hospital in Tokyo, Japan. Through these experiences he has received expertise in clinical (and basic) hematopoietic cell transplantation. He is also very competent in hematopoietic stem cell biology. After serving as Assistant Professor at the Kyoto University in 2005, Dr. Kobayashi sought to continue his scientific pursuits in stem cell biology at the Indiana University School of Medicine (IUSM). The extensive trainings have enriched his knowledge in both stem cell biology and cancer biology, and further developed his expertise in analyzing stem cell behavior in genetically modified mice. Dr. Kobayashi also has experience with multiple mouse models of human acute myeloid leukemia and myeloproliferative diseases including MLL-AF9-, AML-ETO-, Notch- mutant-cKit- and Ras-induced leukemia. Dr. Kobayashi is currently focusing on embryonic hematopoiesis in collaboration with Dr Yoshimoto, who is an expert of fetal/ embryonic hematopoiesis, and he is currently investigating tissue resident innate immune cells.
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Education and Training
- PhD 2000, Mie University
- MD 1990, Mie University
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Research
- Hematopoietic Stem Cells
- Developmental Hematology
- Childhood Acute Leukemia
- Cellular Immunology
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Publications
Chen H., Bai Y., Kobayashi M., Xiao S., Barajas S., Cai W., Chen S., Miao J., Meke F.N., Yao C., Yang Y., Strube K., Satchivi O., Sun J., Ronnstrand L., Croop J.M., Boswell H.S., Jia Y., Liu H., Li L.S., Altman J.K., Eklund E.A., Sukhanova M., Ji P., Tong W., Band H., Huang D.T., Platanias L.C., Zhang Z.Y., Liu Y. PRL2 Phosphatase Promotes Oncogenic KIT Signaling in Leukemia Cells through Modulating CBL Phosphorylation Molecular Cancer Research. 2024;22:94-103.
Chen H., Bai Y., Kobayashi M., Xiao S., Cai W., Barajas S., Chen S., Miao J., Meke F.N., Vemula S., Ropa J.P., Croop J.M., Boswell H.S., Wan J., Jia Y., Liu H., Li L.S., Altman J.K., Eklund E.A., Ji P., Tong W., Band H., Huang D.T., Platanias L.C., Zhang Z.Y., Liu Y. PRL2 phosphatase enhances oncogenic FLT3 signaling via dephosphorylation of the E3 ubiquitin ligase CBL at tyrosine 371 Blood. 2023;141:244-259.
Kobayashi M., Wei H., Yamanashi T., Azevedo Portilho N., Cornelius S., Valiente N., Nishida C., Cheng H., Latorre A., Zheng W.J., Kang J., Seita J., Shih D.J., Wu J.Q., Yoshimoto M. HSC-independent definitive hematopoiesis persists into adult life Cell Reports. 2023;42(3)
Kobayashi M., Yoshimoto M. Multiple waves of fetal-derived immune cells constitute adult immune system Immunological Reviews. 2023;315(1):11-30.
Banerjee P., Olmsted-Davis E.A., Deswal A., Nguyen M.T., Koutroumpakis E., Palaskas N.L., Lin S.H., Kotla S., Reyes-Gibby C., Yeung S.C.J., Yusuf S.W., Yoshimoto M., Kobayashi M., Yu B., Schadler K., Herrmann J., Cooke J.P., Jain A., Chini E., Le N.T., Abe J.I. Cancer treatment-induced NAD<sup>+</sup> depletion in premature senescence and late cardiovascular complications Journal of Cardiovascular Aging. 2022;2
Imanishi M., Cheng H., Kotla S., Deswal A., Le N.T., Chini E., Ko K.A., Samanthapudi V.S.K., Lee L.L., Herrmann J., Xu X., Reyes-Gibby C., Yeung S.C.J., Schadler K.L., Yusuf S.W., Liao Z., Nurieva R., Amir E.a.D., Burks J.K., Palaskas N.L., Cooke J.P., Lin S.H., Kobayashi M., Yoshimoto M., Abe J.I. Radiation therapy induces immunosenescence mediated by p90RSK Frontiers in Cardiovascular Medicine. 2022;9
Yoshimoto M., Kosters A., Cornelius S., Valiente N., Cheng H., Latorre A., Nishida C., Ghosn E.E.B., Kobayashi M. Mast Cell Repopulating Ability Is Lost During the Transition From Pre-HSC to FL HSC Frontiers in Immunology. 2022;13
Ding J., Cardoso A.A., Yoshimoto M., Kobayashi M. The Earliest T-Precursors in the Mouse Embryo Are Susceptible to Leukemic Transformation Frontiers in Cell and Developmental Biology. 2021;9
Portilho N.A., Scarfo R., Bertesago E., Ismailoglu I., Kyba M., Kobayashi M., Ditadi A., Yoshimoto M. B1 lymphocytes develop independently of Notch signaling during mouse embryonic development Development (Cambridge). 2021;148(15)
Yu H., Gao R., Chen S., Liu X., Wang Q., Cai W., Vemula S., Fahey A.C., Henley D., Kobayashi M., Liu S.Z., Qian Z., Kapur R., Broxmeyer H.E., Gao Z., Xi R., Liu Y. Bmi1 Regulates Wnt Signaling in Hematopoietic Stem and Progenitor Cells Stem Cell Reviews and Reports. 2021;17:2304-2313.
Chen S., Wang Q., Yu H., Capitano M.L., Vemula S., Nabinger S.C., Gao R., Yao C., Kobayashi M., Geng Z., Fahey A., Henley D., Liu S.Z., Barajas S., Cai W., Wolf E.R., Ramdas B., Cai Z., Gao H., Luo N., Sun Y., Wong T.N., Link D.C., Liu Y., Boswell H.S., Mayo L.D., Huang G., Kapur R., Yoder M.C., Broxmeyer H.E., Gao Z., Liu Y. Author Correction: Mutant p53 drives clonal hematopoiesis through modulating epigenetic pathway (Nature Communications, (2019), 10, 1, (5649), 10.1038/s41467-019-13542-2) Nature Communications. 2020;11(1)
Kobayashi M., Lin Y., Mishra A., Shelly C., Gao R., Reeh C.W., Wang P.Z., Xi R., Liu Y., Wenzel P., Ghosn E., Liu Y., Yoshimoto M. Bmi1 maintains the self-renewal property of innate-like B lymphocytes Journal of Immunology. 2020;204(12):3262-3272.
Kobayashi M., Yoshimoto M. A Modified Semisolid Clonal Culture for Identification of B-1 and B-2 Progenitor Colony Forming Ability of Mouse Embryonic Hemogenic Endothelial Cells Bio-protocol. 2020;10(9)
Azevedo Portilho N., Kobayashi M., Yoshimoto M. What do the lineage tracing studies tell us? Consideration for hematopoietic stem cell origin, dynamics, and leukemia-initiating cells International Journal of Hematology. 2019;109(1):35-40.
Chen S., Wang Q., Yu H., Capitano M.L., Vemula S., Nabinger S.C., Gao R., Yao C., Kobayashi M., Geng Z., Fahey A., Henley D., Liu S.Z., Barajas S., Cai W., Wolf E.R., Ramdas B., Cai Z., Gao H., Luo N., Sun Y., Wong T.N., Link D.C., Liu Y., Boswell H.S., Mayo L.D., Huang G., Kapur R., Yoder M.C., Broxmeyer H.E., Gao Z., Liu Y. Mutant p53 drives clonal hematopoiesis through modulating epigenetic pathway Nature Communications. 2019;10(1)
Kobayashi M., Tarnawsky S.P., Wei H., Mishra A., Azevedo Portilho N., Wenzel P., Davis B., Wu J., Hadland B., Yoshimoto M. Hemogenic Endothelial Cells Can Transition to Hematopoietic Stem Cells through a B-1 Lymphocyte-Biased State during Maturation in the Mouse Embryo Stem Cell Reports. 2019;13(1):21-30.
Lin Y., Kobayashi M., Azevedo Portilho N., Mishra A., Gao H., Liu Y., Wenzel P., Davis B., Yoder M.C., Yoshimoto M. Long-Term Engraftment of ESC-Derived B-1 Progenitor Cells Supports HSC-Independent Lymphopoiesis Stem Cell Reports. 2019;12(3):572-583.
Nabinger S., Chen S., Gao R., Yao C., Kobayashi M., Vemula S., Fahey A., Wang C., Daniels C., Boswell H., Sandusky G., Mayo L., Kapur R., Liu Y. Mutant p53 enhances leukemia-initiating cell self-renewal to promote leukemia development Leukemia. 2019;33(6):1535-1539.
Chen S., Gao R., Yao C., Kobayashi M., Liu S., Yoder M., Broxmeyer H., Kapur R., Boswell H., Mayo L., Liu Y. Genotoxic stresses promote clonal expansion of hematopoietic stem cells expressing mutant p53 Leukemia. 2018;32(3):850-854.
Spidale N.A., Sylvia K., Narayan K., Miu B., Frascoli M., Melichar H.J., Zhihao W., Kisielow J., Palin A., Serwold T., Love P., Kobayashi M., Yoshimoto M., Jain N., Kang J. Interleukin-17-Producing γδ T Cells Originate from SOX13<sup>+</sup> Progenitors that Are Independent of γδTCR Signaling Immunity. 2018;49(5):857-872.e5.
Chen S., Gao R., Kobayashi M., Yu H., Yao C., Kapur R., Yoder M., Liu Y. Pharmacological inhibition of AKT activity in human CD34<sup>+</sup> cells enhances their ability to engraft immunodeficient mice Experimental Hematology. 2017;45:74-84.
Kobayashi M., Bai Y., Chen S., Gao R., Yao C., Cai W., Cardoso A.A., Croop J., Zhang Z.Y., Liu Y. Phosphatase PRL2 promotes oncogenic NOTCH1-Induced T-cell leukemia Leukemia. 2017;31(3):751-754.
Kobayashi M., Chen S., Bai Y., Yao C., Gao R., Sun X., Mu C., Twiggs T., Yu Z., Boswell H., Yoder M., Kapur R., Mulloy J., Zhang Z., Liu Y. Phosphatase PRL2 promotes AML1-ETO-induced acute myeloid leukemia Leukemia. 2017;31(6):1453-1457.
Kobayashi M., Nabinger S., Bai Y., Yoshimoto M., Gao R., Chen S., Yao C., Dong Y., Zhang L., Rodriguez S., Yashiro-Ohtani Y., Pear W., Carlesso N., Yoder M., Kapur R., Kaplan M., Daniel Lacorazza H., Zhang Z., Liu Y. Protein Tyrosine Phosphatase PRL2 Mediates Notch and Kit Signals in Early T Cell Progenitors Stem Cells. 2017;35(4):1053-1064.
Yao C., Kobayashi M., Chen S., Nabinger S.C., Gao R., Liu S.Z., Asai T., Liu Y. Necdin modulates leukemia-initiating cell quiescence and chemotherapy response Oncotarget. 2017;8(50):87607-87622.
Ghosh J., Kobayashi M., Ramdas B., Chatterjee A., Ma P., Mali R.S., Carlesso N., Liu Y., Plas D.R., Chan R.J., Kapur R. S6K1 regulates hematopoietic stem cell self-renewal and leukemia maintenance Journal of Clinical Investigation. 2016;126(7):2621-2625.
Gao R., Chen S., Kobayashi M., Yu H., Zhang Y., Wan Y., Young S.K., Soltis A., Yu M., Vemula S., Fraenkel E., Cantor A., Antipin Y., Xu Y., Yoder M.C., Wek R.C., Ellis S.R., Kapur R., Zhu X., Liu Y. Bmi1 promotes erythroid development through regulating ribosome biogenesis Stem Cells. 2015;33(3):925-938.
Chatterjee A., Ghosh J., Ramdas B., Mali R.S., Martin H., Kobayashi M., Vemula S., Canela V.H., Waskow E.R., Visconte V., Tiu R.V., Smith C.C., Shah N., Bunting K.D., Boswell H.S., Liu Y., Chan R.J., Kapur R. Regulation of Stat5 by FAK and PAK1 in Oncogenic FLT3- and KIT-Driven Leukemogenesis Cell Reports. 2014;9(4):1333-1348.
Chitteti B.R., Kobayashi M., Cheng Y., Zhang H., Poteat B.A., Broxmeyer H.E., Pelus L.M., Hanenberg H., Zollman A., Kamocka M.M., Carlesso N., Cardoso A.A., Kacena M.A., Srour E.F. CD166 regulates human and murine hematopoietic stem cells and the hematopoietic niche Blood. 2014;124(4):519-529.
Kobayashi M., Bai Y., Dong Y., Yu H., Chen S., Gao R., Zhang L., Yoder M., Kapur R., Zhang Z., Liu Y. PRL2/PTP4A2 phosphatase is important for hematopoietic stem cell self-renewal Stem Cells. 2014;32(7):1956-1967.
Kobayashi M., Chen S., Gao R., Bai Y., Zhang Z., Liu Y. Phosphatase of regenerating liver in hematopoietic stem cells and hematological malignancies Cell Cycle. 2014;13(18):2827-2835.
Kobayashi M., Shelley W.C., Seo W., Vemula S., Lin Y., Liu Y., Kapur R., Taniuchi I., Yoshimoto M. Functional B-1 progenitor cells are present in the hematopoietic stem cell-deficient embryo and depend on Cbfβ for their development Proceedings of the National Academy of Sciences of the United States of America. 2014;111(33):12151-12156.
Kobayashi M., Srour E.F. Regulation of murine hematopoietic stem cell quiescence by Dmtf1 Blood. 2011;118(25):6562-6571.
Hiramatsu H., Morishima T., Nakanishi H., Mizushima Y., Miyazaki M., Matsubara H., Kobayashi M., Nakahata T., Adachi S. Successful treatment of a patient with Klinefelter's syndrome complicated by mediastinal germ cell tumor and AML(M7) Bone Marrow Transplantation. 2008;41(10):907-908.
Matsubara H., Kobayashi M., Yui Y., Kato I., Niwa A., Arai M., Miyazaki M., Mizushima Y., Umeda K., Hiramatsu H., Watanabe K.i., Adachi S., Nakahata T. Continuous infusion of cyclosporine A and C3 monitoring in pediatric stem cell transplantation [Rinshō ketsueki] The Japanese journal of clinical hematology. 2007;48(8):605-610.
Niwa A., Matsubara H., Adachi S., Fujino H., Higashi Y., Umeda K., Shiota M., Hiramatsu H., Kobayashi M., Watanabe K.I., Yorifuji T., Nakahata T. Diabetes mellitus after stem cell transplantation in a patient with acute lymphoblastic leukemia: Possible association with tacrolimus Pediatrics International. 2007;49(4):530-532.
Yoshihara T., Okada K., Kobayashi M., Kikuta A., Kato K., Adachi N., Kikuchi A., Ishida H., Hirota Y., Kuroda H., Nagatoshi Y., Inukai T., Koike K., Kigasawa H., Yagasaki H., Tokuda K., Kishimoto T., Nakano T., Fujita N., Goto H., Nakazawa Y., Kanegane H., Matsuzaki A., Osugi Y., Hasegawa D., Uoshima N., Nakamura K., Tsuchida M., Tanaka R., Watanabe A., Yabe H. Outcome of non-T-cell-depleted HLA-haploidentical hematopoietic stem cell transplantation from family donors in children and adolescents International Journal of Hematology. 2007;85(3):246-255.
Matsubara H., Kobayashi M., Tokumasu M., Nakanishi H., Miyazaki M., Mizushima Y., Hiramatsu H., Adachi S., Nakayama T., Onishi E., Nakahata T. Salmonella enteritidis septic arthritis after allogeneic peripheral blood stem cell transplantation [15] Leukemia and Lymphoma. 2006;47(7):1435-1437.
Mizumoto H., Hata D., Yamamoto K., Shirakawa R., Kumakura A., Shiota M., Yokoyama A., Matsubara H., Kobayashi M., Nishikomori R., Adachi S., Nakahata T., Kita T., Horiuchi H., Yasukawa M., Ishii E. Familial hemophagocytic lymphohistiocytosis with the MUNC13-4 mutation: A case report European Journal of Pediatrics. 2006;165(6):384-388.
Yamamoto A., Miki Y., Adachi S., Kanagaki M., Fushimi Y., Okada T., Kobayashi M., Hiramatsu H., Umeda K., Nakahata T., Van Buchem M.A., Togashi K. Whole brain magnetization transfer histogram analysis of pediatric acute lymphoblastic leukemia patients receiving intrathecal methotrexate therapy European Journal of Radiology. 2006;57(3):423-427.
Kasahara M., Ueda M., Haga H., Hiramatsu H., Kobayashi M., Adachi S., Sakamoto S., Oike F., Egawa H., Takada Y., Tanaka K. Living-donor liver transplantation for hepatoblastoma American Journal of Transplantation. 2005;5(9):2229-2235.
Matsubara H., Adachi S., Yano J., Kitamura N., Miyazaki M., Mizushima Y., Hiramatsu H., Kobayashi M., Nakahata T. Successful allogeneic bone marrow transplantation in a patient with acute myelogenous leukemia and cytomegalovirus retinitis International Journal of Hematology. 2004;80(2):190-192.
Matsubara H., Watanabe K.i., Sakai H., Chang H., Fujino H., Higashi Y., Kobayashi M., Adachi S., Seto S., Nakahata T. Rapid improvement of paraplegia caused by epidural involvements of Burkitt's lymphoma with chemotherapy. Spine. 2004;29(1)
Tanaka T., Matsubara H., Adachi S., Chang H., Fujino H., Higashi Y., Yasumi T., Kobayashi M., Watanabe K.I., Takahashi M., Kobayashi Y., Maruya E., Saji H., Nakahata T. Second transplantation from HLA 2-loci-mismatched mother for graft failure due to hemophagocytic syndrome after cord blood transplantation International Journal of Hematology. 2004;80(5):467-469.
Toyoda H., Ido M., Hori H., Hiraiwa H., Hirayama M., Kobayashi M., Ogawa M., Miyahara M., Iwamoto S., Hayashi T., Gabazza E.C., Suzuki K., Azuma E., Komada Y. A case of juvenile myelomonocytic leukemia with concomitant cytomegalovirus infection Journal of Pediatric Hematology/Oncology. 2004;26(9):606-608.
Iwamoto S., Azuma E., Hori H., Hirayama M., Kobayashi M., Komada Y., Nishimori H., Miyahara M., Nishide Y. BK virus-associated fatal renal failure following late-onset hemorrhagic cystitis in an unrelated bone marrow transplantation Pediatric Hematology and Oncology. 2002;19(4):255-261.
Azuma E., Hirayama M., Bonno M., Iwamoto S., Kumamoto T., Kobayashi M., Komada Y., Taniguchi K., Nakano T., Kamiya H. Successful immunization following cord blood transplantation in a child with Diamond-Blackfan anemia Pediatric Hematology and Oncology. 2001;18(3):193-197.
Jiang Q., Azuma E., Hirayama M., Iwamoto S., Kumamoto T., Kobayashi M., Yamamoto H., Sakurai M., Komada Y. Functional immaturity of cord blood monocytes as detected by impaired response to hepatocyte growth factor Pediatrics International. 2001;43(4):334-339.
Jiang Q., Azuma E., Tanaka M., Kobayashi M., Hirayama M., Kumamoto T., Iwamoto S., Yamamoto H., Nakashima K., Sakurai M., Komada Y. Differential responsiveness of cord and adult blood monocytes to hepatocyte growth factor Clinical and Experimental Immunology. 2001;125(2):222-228.
Kobayashi M., Azuma E., Ido M., Hirayama M., Jiang Q., Iwamoto S., Kumamoto T., Yamamoto H., Sakurai M., Komada Y. A pivotal role of Rho GTPase in the regulation of morphology and function of dendritic cells Journal of Immunology. 2001;167(7):3585-3591.
Toyoda H., Azuma E., Hori H., Hirayama M., Kobayashi M., Isogai K., Kondo N., Komada Y. Successful unrelated BMT in a patient with Kostmann syndrome complicated by pre-transplant pulmonary 'bacterial' abscesses Bone Marrow Transplantation. 2001;28(4):413-415.
Hirayama M., Azuma E., Jiang Q., Kobayashi M., Iwamoto S., Kumamoto T., Kisenge R., Yamamoto H., Komada Y. Parvovirus B19 transmitted by bone marrow British Journal of Haematology. 2000;111(2):659-661.
Hirayama M., Azuma E., Jiang Q., Kobayashi M., Iwamoto S., Kumamoto T., Kisenge R., Yamamoto H., Komada Y. The reconstitution of CD45RB<sup>hi</sup>CD4<sup>+</sup> naive T cells is inversely correlated with donor age in murine allogeneic haematopoietic stem cell transplantation British Journal of Haematology. 2000;111(2):700-707.
Miyahara M., Azuma E., Hirayama M., Kobayashi M., Hori H., Komada Y., Masuda H. Somnolence syndrome in a child following 1200-cGy total body irradiation in an unrelated bone marrow transplantation Pediatric Hematology and Oncology. 2000;17(6):489-495.
Kumamoto T., Azuma E., Tanaka M., Qi J., Hirayama M., Zhang S.L., Kobayashi M., Iwamoto S., Komada Y., Yamamoto H., Nakashima K., Sakurai M. Human dendritic cells express the thrombopoietin receptor, c-Mpl British Journal of Haematology. 1999;105(4):1025-1033.
Hirayama M., Azuma E., Kumamoto T., Qi J., Kobayashi M., Komada Y., Inui T., Miyake M., Mugishima H., Hamazaki M., Sakurai M. Late-onset unilateral renal dysfunction combined with non-insulin-dependent diabetes mellitus and bronchial asthma following allogeneic bone marrow transplantation for acute lymphoblastic leukemia in a child Bone Marrow Transplantation. 1998;22(9):923-926.
Umemoto M., Azuma E., Hirayama M., Nagai M., Hiratake S., Qi J., Kumamoto T., Kobayashi M., Komada Y., Sakurai M. Cytokine-enhanced mixed lymphocyte reaction (MLR) in cord blood Clinical and Experimental Immunology. 1998;112(3):459-463.