My research projects aim to investigate the biology of human leukemia. I believe my research will contribute to clarify the disease pathogenesis of leukemia that leads to overcome the disease.
Honors & Awards
Overseas Award, Nakayama Foundation for Human Science (2014)
Doctor of Philosophy, The University of Tokyo, Pathology, Immunology, Microbiology (2014)
Doctor of Medicine, Asahikawa Medical College (2005)
Ravindra Majeti, Postdoctoral Faculty Sponsor
Current Research and Scholarly Interests
My experience as a clinical hematologist has highlighted the importance of scientific advances that started in a laboratory can transform the lives of many patients. While many of my patients were cured of their disease with allogeneic hematopoietic stem cell transplantation, underscoring the importance of anti-tumor immunotherapy in eradicating leukemia, I witnessed face-to-face their suffering from the long-term consequence of graft-versus-host disease (GVHD). For this reason, I embarked on a PhD program to design antibody therapy to (i) target GVHD and (ii) target hematological malignancies. Under the mentorship of Professor Hiromitsu Nakauchi, a world leader in hematopoiesis and antibody therapies, I developed specific monoclonal antibodies for severe GVHD (Nakauchi et al., Exp Hematol, 2015). It was my PhD student experience and unique skill set, that prompted me to undertake a postdoctoral fellowship in the laboratory of Professor Ravindra Majeti, Department of Hematology, Stanford University School of Medicine. It was the success of my PhD experience and unique skrew sets are developed that prompted me to further my research. Instead of targeting GVHD, targeting leukemia stem cells. Since I moved to Majeti lab, I have developed a unique human system of mimicking a leukemia stem cell by infecting cord blood hematopoietic stem/progeny cells with mutant and knock down genes that phenocopy leukemic stem cells. These novel techniques developed in own laboratory will allow us to design affected treatments against leukemias.
Through these experiences, I have acquired various experimental skills such as 1) multicolor FACS analysis and clone-sorting techniques, 2) generation of monoclonal antibodies, 3) generation of transgenic mice, 4) transplantation techniques using human or mouse hematopoietic stem cells and other methods of general molecular and cellular biology.
I am committed to a life-long career in hematology research and improving the lives of hematology patients.
Effective treatment against severe graft-versus-host disease with allele-specific anti-HLA monoclonal antibody in a humanized mouse model.
2015; 43 (2): 79-88 e4
Graft-versus-host disease (GVHD), mediated by donor-derived alloreactive T cells, is a major cause of non-relapse mortality in allogeneic hematopoietic stem-cell transplantation (allo-HSCT). Its therapy is not well-defined. We established allele-specific anti-HLA monoclonal antibodies (ASHmAbs) that specifically target HLA molecules, with steady death of target-expressing cells. One such ASHmAb, against HLA-A*02:01 (A2-kASHmAb), was examined in a xenogeneic GVHD mouse model. To induce fatal GVHD, non-irradiated NOD/Shi-scid/IL-2Rγ(null) (NOG) mice were injected with healthy-donor human peripheral blood mononuclear cells (PBMCs), some expressing HLA-A*02:01, some not. Administration of A2-kASHmAb promoted the survival of mice injected with HLA-A*02:01-expressing PBMCs (p<0.0001) and, in humanized NOG mice, immediately cleared HLA-A*02:01-expressing human blood cells from mouse peripheral blood. Human PBMCs were again detectable in mouse blood 2-4 weeks after A2-kASHmAb administration, suggesting that kASHmAb may be safely administered to GVHD patients without permanently ablating the graft. This approach, different from those of existing GVHD pharmacotherapy, may open a new door for treatment of GVHD in HLA-mismatched allo-HSCT.
View details for DOI 10.1016/j.exphem.2014.10.008
View details for PubMedID 25448490
Concurrent administration of intravenous systemic and intravitreal methotrexate for intraocular lymphoma with central nervous system involvement
INTERNATIONAL JOURNAL OF HEMATOLOGY
2010; 92 (1): 179-185
Intraocular lymphoma (IOL) is rare lymphoma that frequently infiltrates the central nervous system (CNS). An optimal treatment has not been established, and its prognosis is quite poor. We treated three IOL patients with CNS involvement by concurrent administration of intravenous and intravitreal methotrexate (MTX) injection. The intraocular lesion responded in all patients. One patient achieved complete response (CR), whereas the other 2 patients were in partial response for CNS lesion, added whole brain radiation and achieved CR. In 3 eyes of 2 patients, an intravitreal MTX injection (vMTX) was administered 2 h after a systemic MTX injection (sMTX) and the intravitreal MTX concentration was measured twice: 2 h after sMTX and 24 h after vMTX. The half-life of MTX in the vitreous fluid was estimated to be 12.4-21.5 h by assuming the first-order elimination kinetics. Although the concentration was still high 24 h after vMTX (69.94-82.89 muM), there were no ocular complications. The serum MTX concentration was not influenced by adding vMTX to sMTX. Grade 3 adverse event, leukocytopenia, was observed in only 1 patient. No grade 4 event was observed. Although further evaluation is required, concurrent sMTX and vMTX may be effective for IOL with CNS involvement.
View details for DOI 10.1007/s12185-010-0589-6
View details for Web of Science ID 000280578700024
View details for PubMedID 20464643