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. Various molecular metabolisms have recently come into focus as novel regulatory elements of stem cell maintenance. The broad objective of the current project 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). Our studies are designed to uncover a function for metabolism in the control of hematopoietic asymmetric division and maintenance, which will in turn lead to novel therapeutic approaches to fine-tuning the function of normal hematopoietic stem cells, and possibly leukemia and other tissue stem cells.
Other studies in the laboratory are 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;
- Arai F, Hirao A, Ohmura M, Sato H, Matsuoka S, Takubo K, Ito K, Koh GY, Suda T. Tie2/angiopoietin-1 signaling regulates hematopoietic stem cell quiescence in the bone marrow niche. Cell 2004:118:149-161.
- Ito K, Hirao A, Arai F, Matsuoka S, Takubo K, Hamaguchi I, Nomiyama K, Hosokawa K, Sakurada K, Nakagata N, Ikeda Y, Tak W. Mak, Suda T. Regulation of oxidative stress by ATM is required for self-renewal of haematopoietic stem cells. Nature 2004:431:997-1001.
- Ito K, Hirao A, Takubo K, Arai F, Matsuoka S, Nomiyama K, Hosokawa K, Nakagata N, Tak W. Mak, Suda T. Reactive oxygen species act through p38 MAPK to limit the lifespan of hematopoietic stem cells. Nat Med. 2006:12:446-451.
- Ito K, Bernardi R, Morotti A, Matsuoka S, Ikeda Y, Rosenblatt J, Avigan DE, Feldstein JT, Pandolfi PP. PML targeting eradicates quiescent leukaemia-initiating cells. Nature 2008:453:1072-1078.
- Maeda T*, Ito K*, Merghoub T, Poliseno L, Hobbs RM, Wang G, Dong L, Dore LC, Zelent A, Luzzatto L, Feldstein JT, Weiss MJ, Pandolfi PP. LRF Is an Essential Downstream Target of GATA1 in Erythroid Development and Regulates BIM-Dependent Apoptosis. Dev Cell. 2009:17:527-540. *Contributed equally to this work.
- Giorgi C, Ito K, Lin HK, Santangelo C, Bernardi R, Rizzuto R, Tacchetti C, Pinton P, Pandolfi PP. Essential role of PML in the regulation of Ca2+-dependent apoptosis at endoplasmic reticulum–mitochondria contact sites. Science. 2010:330:1247-1251.
- Garcia-Cao I, Song MS, Hobbs RM, Laurent G, Giorgi C, de Boer VCJ, Anastasiou D, Ito K, Sasaki A, Rameh L, Carracedo A, Vander Heiden MG, Cantley LC, Pinton P, Haigis MD, Pandolfi PP. Systemic super-elevation of PTEN induces an anti-Warburg tumor suppressive metabolic state. Cell. 2012:149:49-62.
- Ito K*, Carracedo A*, Weiss D, Arai F, Ala U, Avigan DE, Schafer ZT, Evans RM, Suda T, Lee CH, Pandolfi PP. A PML–PPAR-δ pathway for fatty acid oxidation regulates hematopoietic stem cell maintenance. Nat Med. 2012:18:1350-1358. *Contributed equally to this work.
- Stroopinsky D*, Rosenblatt J*, Ito K, Mills H, Yin L, Rajabi H, Vasir B, Kufe T, Luptakova K, Arnason J, Nardella C, Levine JD, Joyce RM, Galinsky I, Reiter Y, Stone RM, Pandolfi PP, Kufe D, Avigan D. MUC1 Is a Potential Target for the Treatment of Acute Myeloid Leukemia Stem Cells. Cancer Res. 2013.
- Kunisaki Y, Bruns I, Scheiermann C, Ahmed J, Pinho S, Zhang D, Mizoguchi T, Wei Q, Lucas D, Ito K, Mar JC, Bergman A, Frenette PS. Arteriolar niches maintain haematopoietic stem cell quiescence.Nature. 2013 Oct 9. doi: 10.1038/nature12612.
- Song SJ*, Ito K*, Ala U, Kats L, Webster K, Sun SM, Jongen-Lavrencic M, Manova-Todorova K, Teruya-Feldstein J, Avigan DE, Delwel R, Pandolfi PP. The Oncogenic MicroRNA miR-22 Targets the TET2 Tumor Suppressor to Promote Hematopoietic Stem Cell Self-Renewal and Transformation. Cell Stem Cell. 2013:13:87-101. doi: 10.1016/j.stem.2013.06.003. *Contributed equally to this work.
Selected Invited articles, Review articles (Review articles)
- 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.
- 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, Ito, K**. Newly identified roles of PML in stem cell biology. Frontier Oncology. 2013 Mar 14. doi: 10.3389/fonc.2013.00050. [Epub ahead of print].
- Weiss, C.N., Ito, K**. DNA damage response, redox status and hematopoiesis. Blood Cells Mol Dis. 2013 Sep 13. doi:pii: S1079-9796(13)00199-X. 10.1016/j.bcmd.2013.08.002. [Epub ahead of print].
More Information About Dr. Keisuke Ito
Ruth L. and David S. Gottesman Institute for Stem Cell and Regenerative Medicine Research
Material in this section is provided by individual faculty members who are solely responsible for its accuracy and content.