Professional Education

  • Doctor of Philosophy, University Of Tokyo (2014)
  • Bachelor of Medicine, Kanazawa University (2005)

Stanford Advisors

  • Joy Wu, Postdoctoral Research Mentor
  • Joy Wu, Postdoctoral Faculty Sponsor

All Publications

  • Foxp3(+) regulatory T cells maintain the bone marrow microenvironment for B cell lymphopoiesis NATURE COMMUNICATIONS Pierini, A., Nishikii, H., Baker, J., Kimura, T., Kwon, H., Pan, Y., Chen, Y., Alvarez, M., Strober, W., Velardi, A., Shizuru, J. A., Wu, J. Y., Chiba, S., Negrin, R. S. 2017; 8


    Foxp3(+) regulatory T cells (Treg cells) modulate the immune system and maintain self-tolerance, but whether they affect haematopoiesis or haematopoietic stem cell (HSC)-mediated reconstitution after transplantation is unclear. Here we show that B-cell lymphopoiesis is impaired in Treg-depleted mice, yet this reduced B-cell lymphopoiesis is rescued by adoptive transfer of affected HSCs or bone marrow cells into Treg-competent recipients. B-cell reconstitution is abrogated in both syngeneic and allogeneic transplantation using Treg-depleted mice as recipients. Treg cells can control physiological IL-7 production that is indispensable for normal B-cell lymphopoiesis and is mainly sustained by a subpopulation of ICAM1(+) perivascular stromal cells. Our study demonstrates that Treg cells are important for B-cell differentiation from HSCs by maintaining immunological homoeostasis in the bone marrow microenvironment, both in physiological conditions and after bone marrow transplantation.

    View details for DOI 10.1038/ncomms15068

    View details for Web of Science ID 000400847300001

    View details for PubMedID 28485401

    View details for PubMedCentralID PMC5436085

  • An All-Recombinant Protein-Based Culture System Specifically Identifies Hematopoietic Stem Cell Maintenance Factors. Stem cell reports Ieyasu, A., Ishida, R., Kimura, T., Morita, M., Wilkinson, A. C., Sudo, K., Nishimura, T., Ohehara, J., Tajima, Y., Lai, C., Otsu, M., Nakamura, Y., Ema, H., Nakauchi, H., Yamazaki, S. 2017


    Hematopoietic stem cells (HSCs) are considered one of the most promising therapeutic targets for the treatment of various blood disorders. However, due to difficulties in establishing stable maintenance and expansion of HSCs in vitro, their insufficient supply is a major constraint to transplantation studies. To solve these problems we have developed a fully defined, all-recombinant protein-based culture system. Through this system, we have identified hemopexin (HPX) and interleukin-1α as responsible for HSC maintenance in vitro. Subsequent molecular analysis revealed that HPX reduces intracellular reactive oxygen species levels within cultured HSCs. Furthermore, bone marrow immunostaining and 3D immunohistochemistry revealed that HPX is expressed in non-myelinating Schwann cells, known HSC niche constituents. These results highlight the utility of this fully defined all-recombinant protein-based culture system for reproducible in vitro HSC culture and its potential to contribute to the identification of factors responsible for in vitro maintenance, expansion, and differentiation of stem cell populations.

    View details for DOI 10.1016/j.stemcr.2017.01.015

    View details for PubMedID 28238792

  • Loss of Gsa in the Postnatal Skeleton Leads to Low Bone Mass and a Blunted Response to Anabolic Parathyroid Hormone Therapy. journal of biological chemistry Sinha, P., Aarnisalo, P., Chubb, R., Poulton, I. J., Guo, J., Nachtrab, G., Kimura, T., Swami, S., Saeed, H., Chen, M., Weinstein, L. S., Schipani, E., Sims, N. A., Kronenberg, H. M., Wu, J. Y. 2016; 291 (4): 1631-1642


    Parathyroid hormone (PTH) is an important regulator of osteoblast function and is the only anabolic therapy currently approved for treatment of osteoporosis. The PTH receptor (PTHR1) is a G protein-coupled receptor that signals via multiple G proteins including Gsα. Mice expressing a constitutively active mutant PTHR1 exhibited a dramatic increase in trabecular bone that was dependent upon expression of Gsα in the osteoblast lineage. Postnatal removal of Gsα in the osteoblast lineage (P-GsαOsxKO mice) yielded markedly reduced trabecular and cortical bone mass. Treatment with anabolic PTH(1-34) (80 μg/kg/day) for 4 weeks failed to increase trabecular bone volume or cortical thickness in male and female P-GsαOsxKO mice. Surprisingly, in both male and female mice, PTH administration significantly increased osteoblast numbers and bone formation rate in both control and P-GsαOsxKO mice. In mice that express a mutated PTHR1 that activates adenylyl cyclase and protein kinase A (PKA) via Gsα but not phospholipase C (PLC) via Gq/11 (D/D mice), PTH significantly enhanced bone formation, indicating that PLC activation is not required for increased bone turnover in response to PTH. Therefore while the anabolic effect of intermittent PTH treatment on trabecular bone volume is blunted by deletion of Gsα in osteoblasts, PTH can stimulate osteoblast differentiation and bone formation. Together these findings suggest that alternative signaling pathways beyond Gsα and Gq/11 act downstream of PTH on osteoblast differentiation.

    View details for DOI 10.1074/jbc.M115.679753

    View details for PubMedID 26598522