Faculty Profile

Dr. Keisuke Ito, M.D.,  Ph.D.

Keisuke Ito, M.D., Ph.D.

Associate Professor, Department of Cell Biology

Associate Professor, Department of Medicine

Director of Scientific Resources of the Stem Cell Institute

Professional Interests

The central research goal of the Ito Lab is the expansion of our understanding of the regulatory pathways controlling the equilibrium of stem cells, with a special focus on the development of novel therapeutics for hematopoietic disorders. At the core of our work is the process of stem cell division, and the resulting balance between self-renewal or differentiation, which directly impacts tissue homeostasis. We are also devoting increased attention to targeting cellular metabolism as a therapeutic strategy, and have cut a path along the leading edge of research into the role of epigenetic-microRNA crosstalk, including physiologically relevant Ten-eleven translocation, in the pathogenesis of myelodysplastic syndrome. We believe our expertise in stem cell biology, hematology, and the bone marrow microenvironment, combined with our development of new single-cell approaches to tracking stem cell fate in animal models, will together facilitate a major contribution to the improvement of transplantation efficiency and the development of new therapies and treatments, and potentially even cures, for many forms of hematologic pathology.

Selected Publications

Selected Original research and Theoretical treatises; 

  1. Ito K*, Lee J*, Chrysanthou S, Zhao Y, Josephs K, Sato H, Teruya-Feldstein J, Zheng D, Dawlaty MM, Ito K. Non-catalytic roles of Tet2 are essential to regulate hematopoietic stem and progenitor cell homeostasis. Cell Rep. 2019 Sep 3;28(10):2480-2490.e4.
  2. Morganti C, Bonora M, Ito K, Ito K. Electron transport chain complex II sustains high mitochondrial membrane potential in hematopoietic stem and progenitor cells. Stem Cell Res2019 Sep 10;40:101573.
  3. Nachmani D et al. Germline NPM1 mutations lead to altered rRNA 2'-O-methylation and cause dyskeratosis congenita. Nat Genet. 2019 Sep 30. doi: 10.1038/s41588-019-0502-z. [Epub ahead of print].
  4. Morganti C, Bonora M, Ito K. Improving the accuracy of flow cytometric assessment of mitochondrial membrane potential in HSPCs through the inhibition of efflux pumps. J Vis Exp. 2019 Jul 30;(149).
  5. Luo H, Mu WC, Karki R, Chiang HH, Mohrin M, Shin JJ, Ohkubo R, Ito K, Kanneganti TD, Chen D. Mitochondrial Stress-Initiated Aberrant Activation of the NLRP3 Inflammasome Regulates the Functional Deterioration of Hematopoietic Stem Cell Aging. Cell Rep. 2019 Jan 22;26(4):945-954.e4.
  6. Weiss CN, Ito K. microRNA-22 promotes megakaryocyte differentiation through repression of its target, GFI1. Blood Advances.
  7. Bonora M, Ito K, Morganti C, Pinton P, Ito K. Membrane-potential compensation reveals mitochondrial volume expansion during HSC commitment. Exp Hematol. 2018 Dec;68:30-37.e1. 
  8. Guarnerio J, Mendez LM, Asada N, Menon AV, Fung J, Berry K, Frenette PS, Ito K, Pandolfi PP. A non-cell-autonomous role for Pml in the maintenance of leukemia from the niche. Nat Commun. 2018 Jan 4;9(1):66.
  9. Turcotte R, Alt C, Runnels JM, Ito K, Wu JW, Zaher W, Mortensen LJ, Silberstein L, Côté DC, Kung AL, Ito K, Lin CP. Image-guided transplantation of single cells in the bone marrow of live animals. Sci Rep. 2017 Jun 20;7(1):3875. 
  10. Ito K, Turcotte R, Cui J, Zimmerman SE, Pinho S, Mizoguchi T, Arai F, Runnels JM, Alt C, Teruya-Feldstein J, Mar JC, Singh R, Suda T, Lin CP, Frenette PS, Ito K. Self-renewal of a purified Tie2+ hematopoietic stem cell population relies on mitochondrial clearance. Science. 2016 Dec 2;354(6316):1156-1160. 
  11. Santos MA, Faryabi RB, Ergen AV et al. DNA-damage-induced differentiation of leukaemic cells as an anti-cancer barrier. Nature. 2014 Oct 2;514(7520):107-11.
  12. Papa A, Wan L, Bonora M et al. Cancer-associated PTEN mutants act in a dominant-negative manner to suppress PTEN protein function. Cell. 2014 Apr 24;157(3):595-610. 
  13. Song SJ*, Ito K* et al. The oncogenic microRNA miR-22 targets the TET2 tumor suppressor to promote hematopoietic stem cell self-renewal and transformation. Cell Stem Cell. 2013 Jul 3;13(1):87-101. *Contributed equally to this work.
  14. 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 31;502(7473):637-43.
  15. Stroopinsky D, Rosenblatt J, Ito K, Mills H et al. MUC1 is a potential target for the treatment of acute myeloid leukemia stem cells. Cancer Res. 2013 Sep 1;73(17):5569-79.
  16. Ito K*, Carracedo A* et al. A PML–PPAR-δ pathway for fatty acid oxidation regulates hematopoietic stem cell maintenance. Nat Med. 2012 Sep;18(9):1350-8. *Contributed equally to this work.
  17. Garcia-Cao I, Song MS, Hobbs RM, Laurent G, Giorgi C, de Boer VC, Anastasiou D, Ito K et al. Systemic elevation of PTEN induces a tumor-suppressive metabolic state. Cell. 2012 Mar 30;149(1):49-62. 
  18. Giorgi C, Ito K et al. PML regulates apoptosis at endoplasmic reticulum by modulating calcium release. Science. 2010 Nov 26;330(6008):1247-51. 
  19. Maeda T*, Ito K* et al. LRF is an essential downstream target of GATA1 in erythroid development and regulates BIM-dependent apoptosis. Dev Cell. 2009 Oct;17(4):527-40. *Contributed equally to this work.
  20. Ito K, Bernardi R et al.PML targeting eradicates quiescent leukaemia-initiating cells. Nature. 2008 Jun 19;453:1072-8. 
  21. Miyamoto K, Araki KY, Naka K, Arai F, Takubo K, Yamazaki S, Matsuoka S, Miyamoto T, Ito K et al. Foxo3a is essential for maintenance of the hematopoietic stem cell pool. Cell Stem Cell. 2007 Jun 7;1(1):101-12.  
  22. Ito K*, Hirao A* et al.Reactive oxygen species act through p38 MAPK to limit the lifespan of hematopoietic stem cells. Nat Med. 2006 Apr;12(4):446-51. *Contributed equally to this work.
  23. Ito K*, Hirao A* et al. Regulation of oxidative stress by ATM is required for self-renewal of haematopoietic stem cells. Nature. 2004 Oct 21;431(7011):997-1002. *Contributed equally to this work.
  24. 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 Jul 23;118(2):149-61.

Selected Invited articles and Review articles 

  1. Ito K, Bonora M, Ito K. Metabolism as master of hematopoietic stem cell fate. Int J Hematol. 2019 Jan;109(1):18-27.
  2. Ito K, Ito K. Hematopoietic stem cell fate through metabolic control. Exp Hematol. 2018 Aug;64:1-11. 
  3. Weiss CN, Ito K. A Macro View of MicroRNAs: The Discovery of MicroRNAs and Their Role in Hematopoiesis and Hematologic Disease. Int Rev Cell Mol Biol. 2017;334:99-175.
  4. Ito K*, Frenette PS*. HSC Contribution in Making Steady-State Blood. Immunity. 2016. Sep 20;45(3):464.
  5. Sato H*, Wheat JC*, Steidl U, Ito K. DNMT3A and TET2 in the Pre-Leukemic Phase of Hematopoietic Disorders. Front Oncol. 2016 Aug 22;6:187. 
  6. Ito K, Ito K. Metabolism and the Control of Cell Fate Decisions and Stem Cell Renewal. Annu Rev Cell Dev Biol. 2016 Oct 6;32:399-409. 
  7. Ito K, Ito K. Resistance in the Ribosome: RUNX1, pre-LSCs, and HSPCs. Cell Stem Cell. 2015 Aug 6;17(2):129-31. 
  8. Ito K*, Suda T*. Metabolic requirements for the maintenance of self-renewing stem cells. Nat Rev Mol Cell Biol. 2014 Apr;15(4):243-56. (*Co-corresponding authors.)
  9. Weiss CN, Ito K. DNA damage: a sensible mediator of the differentiation decision in hematopoietic stem cells and in leukemia. Int J Mol Sci. 2015 Mar 17;16(3):6183-201. 
  10. Nakahara F, Weiss CN, Ito K. The role of PML in hematopoietic and leukemic stem cell maintenance. Int J Hematol. 2014 Jul;100(1):18-26. 
  11. Weiss CN, Ito K. DNA damage response, redox status and hematopoiesis. Blood Cells Mol Dis. 2014 Jan;52(1):12-8. 
  12. Ito K, Ito K. Newly Identified Roles of PML in Stem Cell Biology. Front Oncol. 2013 Mar 14;3:50. 
  13. Ito K, Bernardi R, Pandolfi PP. A novel signaling network as a critical rheostat for the biology and maintenance of the normal stem cell and the cancer-initiating cell. Curr Opin Genet Dev. 2009 Feb;19(1):51-9. 

Selected Non-Experimental articles

  1. Ito K. Self-Renewal and Differentiation. The SAGE Encyclopedia of Stem Cell Research. 2015 July:1007-1010.

Organized Research Topic

  1. The Road to Pathogenesis: Charting the Development of (pre-)LSCs. Front Oncol. (Topic Editors: Ito K and Levine RL)

     

Research Support

NIH       1. Lipid metabolism in the maintenance of HSCs

              2. Tet2's role in HSCs and hematologic disorders

              3. Single Cell Approach to uncovering factors regulating HSC division symmetry in vivo

LLS        1. Targeting LSC metabolism for leukemia therapy

Shared Facilities

              Director and Faculty Supervisor, Single Cell Genomics and Computational Analysis core 

 

Selected Events at Einstein Stem Cell Institute (contributed as a (co-)organizer)

More Information About Dr. Keisuke Ito

Dr. Ito's biosketch (Department of Cell Biology)

Einstein Stem Cell Institute

Material in this section is provided by individual faculty members who are solely responsible for its accuracy and content.

Albert Einstein College of Medicine
Michael F. Price Center
1301 Morris Park Avenue , Room 102
Bronx, NY 10461

Tel: 718.678.1278
Fax: 718.678.1018

Research Information