Keisuke Ito, M.D., Ph.D.
Our research interests have focused on biomedical research aiming toward the development of stem cell therapies. In keeping with this commitment, our team’s long-term research goals are to define the critical regulatory pathways in the controlled equilibrium of stem cells, findings which will be relevant to therapy.
One of our main projects is to illuminate through both genetic and pharmacological approaches the role of one such potential regulatory element, cellular metabolism, in the cell fate decisions of hematopoietic stem cells (HSCs). Various molecular metabolisms have recently come into focus as novel regulatory elements of stem cell maintenance.
Another study in the laboratory is investigating the pathogenesis of an incurable stem cell disorder, myelodysplastic syndrome (MDS). Our lab has devised a plan to identify key mechanisms of MDS pathogenesis for the development of targeted therapies to combat the disease more effectively.
Selected Original research and Theoretical treatises;
- Song, S.J.*, Ito, K.*, Ala, U., Kats, L., Webster, K., Sun, S.M., Jongen-Lavrencic, M., Manova-Todorova, K., Teruya-Feldstein, J., Avigan, D.E., et al. (2013). The oncogenic microRNA miR-22 targets the TET2 tumor suppressor to promote hematopoietic stem cell self-renewal and transformation. Cell stem cell 13, 87-101. *Contributed equally to this work.
- Kunisaki, Y., Bruns, I., Scheiermann, C., Ahmed, J., Pinho, S., Zhang, D., Mizoguchi, T., Wei, Q., Lucas, D., Ito, K., et al. (2013). Arteriolar niches maintain haematopoietic stem cell quiescence. Nature 502, 637-643.
- Stroopinsky, D., Rosenblatt, J., Ito, K., Mills, H., Yin, L., Rajabi, H., Vasir, B., Kufe, T., Luptakova, K., Arnason, J., et al. (2013). MUC1 is a potential target for the treatment of acute myeloid leukemia stem cells. Cancer research 73, 5569-5579.
- Ito, K.*, Carracedo, A.*, Weiss, D., Arai, F., Ala, U., Avigan, D.E., Schafer, Z.T., Evans, R.M., Suda, T., Lee, C.H., et al. (2012). A PML-PPAR-delta pathway for fatty acid oxidation regulates hematopoietic stem cell maintenance. Nature medicine 18, 1350-1358. *Contributed equally to this work.
- Garcia-Cao, I., Song, M.S., Hobbs, R.M., Laurent, G., Giorgi, C., de Boer, V.C., Anastasiou, D., Ito, K., Sasaki, A.T., Rameh, L., et al. (2012). Systemic elevation of PTEN induces a tumor-suppressive metabolic state. Cell 149, 49-62.
- Giorgi, C., Ito, K., Lin, H.K., Santangelo, C., Wieckowski, M.R., Lebiedzinska, M., Bononi, A., Bonora, M., Duszynski, J., Bernardi, R., et al. (2010). PML regulates apoptosis at endoplasmic reticulum by modulating calcium release. Science 330, 1247-1251.
- Maeda, T.*, Ito, K.*, Merghoub, T., Poliseno, L., Hobbs, R.M., Wang, G., Dong, L., Maeda, M., Dore, L.C., Zelent, A., et al. (2009). LRF is an essential downstream target of GATA1 in erythroid development and regulates BIM-dependent apoptosis. Developmental cell 17, 527-540. *Contributed equally to this work.
- Ito, K., Bernardi, R., Morotti, A., Matsuoka, S., Saglio, G., Ikeda, Y., Rosenblatt, J., Avigan, D.E., Teruya-Feldstein, J., and Pandolfi, P.P. (2008). PML targeting eradicates quiescent leukaemia-initiating cells. Nature 453, 1072-1078.
- Ito, K.*, Hirao, A.*, Arai, F., Takubo, K., Matsuoka, S., Miyamoto, K., Ohmura, M., Naka, K., Hosokawa, K., Ikeda, Y., et al. (2006). Reactive oxygen species act through p38 MAPK to limit the lifespan of hematopoietic stem cells. Nature medicine 12, 446-451.
- Ito, K.*, Hirao, A.*, Arai, F., Matsuoka, S., Takubo, K., Hamaguchi, I., Nomiyama, K., Hosokawa, K., Sakurada, K., Nakagata, N., et al. (2004). Regulation of oxidative stress by ATM is required for self-renewal of haematopoietic stem cells. Nature 431, 997-1002.
- Arai, F., Hirao, A., Ohmura, M., Sato, H., Matsuoka, S., Takubo, K., Ito, K., Koh, G.Y., and Suda, T. (2004). Tie2/angiopoietin-1 signaling regulates hematopoietic stem cell quiescence in the bone marrow niche. Cell 118, 149-161.
Selected Invited articles and Review articles ($; Correponding author)
- $Ito, K., $Suda, T. Metabolic requirements in the maintenance of self-renewing stem cells. Nature Reviews Molecular Cell Biology in press. (2014 April issue)
- Nakahara, F., Weiss, C.N., and $Ito, K. (2014). The role of PML in hematopoietic and leukemic stem cell maintenance. International journal of hematology.
- Weiss, C.N., and $Ito, K. (2013). DNA damage response, redox status and hematopoiesis. Blood cells, molecules & diseases 52, 8-12.
- Ito, K., and $Ito, K. (2013). Newly Identified Roles of PML in Stem Cell Biology. Frontiers in oncology 3, 50.
- Carracedo, A., Ito, K., and Pandolfi, P.P. (2011). The nuclear bodies inside out: PML conquers the cytoplasm. Current opinion in cell biology 23, 360-366.
- Ito, K., Bernardi, R., and Pandolfi, P.P. (2009). A novel signaling network as a critical rheostat for the biology and maintenance of the normal stem cell and the cancer-initiating cell. Current opinion in genetics & development 19, 51-59.
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