The central research goal of the Ito Lab is the expansion of our understanding of the regulatory pathways controlling the equilibrium of healthy and malignant hematopoietic stem cells. At the core of our work is the process of stem cell division, and the resulting balance between self-renewal and differentiation, which directly impacts tissue homeostasis. We are also devoting increased attention to targeting cellular metabolism and/or mitochondrial physiology as a therapeutic strategy and are cutting 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 single cell approaches and live imaging to track stem cell fate in vivo and leukocyte behavior in sickle cell disease animal models, will facilitate major contributions 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 Original research and Theoretical treatises; 

1.        Wu Q, Zhang J, Kumar S, Shen S, Kincaid M, Johnson CB, Zhang YS, Turcotte R, Alt C, Ito K, Homan S, Sherman BE, Shao TY, Slaughter A, Weinhaus B, Song B, Filippi MD, Grimes HL, Lin CP, Ito K, Way SS, Kofron JM, Lucas D. Resilient anatomy and local plasticity of naive and stress haematopoiesis. Nature. 2024 Mar;627(8005):839-846. doi: 10.1038/s41586-024-07186-6. Epub 2024 Mar 20. PMID: 38509363.

2.        Bonora M*, Morganti C*, van Gastel N*, Zanolla I, Ferroni L, Zhang Y, Jung Y, Sales G, Martini P, Nakamura T, Lasorsa FM, Finkel T, Lin CP, Zavan B, Pinton P, Georgakoudi I, Romaldi C, Scadden DT, Ito K. A mitochondrial NADPH-cholesterol axis regulates extracellular vesicle biogenesis to support HSC fate. Cell Stem Cell. 2024 Mar 7;31(3):359-377.e10. doi: 10.1016/j.stem.2024.02.004. PMID: 38458178.

3.        Flores JC, Ito K, Huang CY, Tang Q, Yanase C, Ito K*, Dawlaty MM*. Comparative analysis of Tet2 catalytic deficient and knockout bone marrow over time. Exp Hematol. 2023 May 22:S0301-472X(23)00227-8. PMID: 37225048.

4.        Missiroli S, Perrone M, Gafà R, …, Ito K, Wieckowski MR, Di Virgilio F, Abelli L, Pinton P, Giorgi C. PML at mitochondria-associated membranes governs a trimeric complex with NLRP3 and P2X7R that modulates the tumor immune microenvironment. Cell Death Differ. 2023 Feb;30(2):429-441. PMID: 36450825 PMCID: PMC9713080.

5.        Morganti C, Ito K, Yanase C, Verma A, TeruyaFeldstein J, Ito K. NPM1 ablation induces HSC aging and inflammation to develop myelodysplastic syndrome exacerbated by p53 loss. EMBO Rep. 2022 May 4;23(5):e54262. doi: 10.15252/embr.202154262. Epub 2022 Mar 1. PMID: 35229971 PMCID: PMC9066051.

6.        Ma L, …, Ito K, Frenette PS, Dawlaty MM. Tet-mediated DNA demethylation regulates specification of hematopoietic stem and progenitor cells during mammalian embryogenesis. Sci Advances. 8, eabm3470 (2022). doi: 10.1126/sciadv.abm3470. PMID: 35235365 PMCID: PMC8890710.

7.        Schönberger K, Obier N, …, Morganti C, Ito K, Ghyselinck NB, Trompouki E, Buescher JM, Pearce EL, Cabezas-Wallscheid N. Multilayer omics analysis reveals a non-classical retinoic acid signaling axis that regulates hematopoietic stem cell identity. Cell Stem Cell. 2022 Jan 6;29(1):131-148.e10. PMID: 34706256.

8.        Wu HC, …, Falini B, Ito K, Martelli MP, de Thé H. Actinomycin D Targets NPM1c-Primed Mitochondria to Restore PML-Driven Senescence in AML Therapy. Cancer Discov. 2021 Dec 1;11(12):3198-3213. doi: 10.1158/2159-8290.CD-21-0177.

9.        Wu JW, …, Mizoguchi T, Ito K, Spencer JA, Lin CP. Intravital fluorescence microscopy with negative contrast. PLoS One. 2021 Aug 5;16(8):e0255204.

10.     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 Res. 2019 Oct;40:101573.

11.      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 Report. 2019 Sep 3;28(10):2480-2490.e4.  Research Briefs (Einstein).

12.      Nachmani D et al. Germline NPM1 mutations lead to altered rRNA 2'-O-methylation and cause dyskeratosis congenita. Nat Genet. 2019 Oct;51(10):1518-1529.

13.      Morganti C, Bonora M, Ito K. Improving the accuracy of flow cytometric assessment of mitochondrial membrane potential in hematopoietic stem and progenitor cells through the inhibition of efflux pumps. J Vis Exp. 2019 Jul 30;(149).

14.      Luo H et al. 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.

15.      Weiss CN, Ito K. microRNA-22 promotes megakaryocyte differentiation through repression of its target, GFI1. Blood Advances. 2019 Jan 8;3:33-46. 

16.      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. 

17.      Guarnerio J, …, 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.

18.      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. 

19.      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;354:1156-1160. 

20.     Santos MA et al. DNA-damage-induced differentiation of leukaemic cells as an anti-cancer barrier. Nature. 2014 Oct 2;514(7520):107-11.

21.     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. 

22.     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.

23.     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.

24.     Stroopinsky D, Rosenblatt J, Ito K 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.

25.     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.

26.     Garcia-Cao I et al. Systemic elevation of PTEN induces a tumor-suppressive metabolic state. Cell. 2012 Mar 30;149(1):49-62. 

27.     Giorgi C, Ito K et al. PML regulates apoptosis at endoplasmic reticulum by modulating calcium release. Science. 2010 Nov 26;330(6008):1247-51. 

28.     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.

29.     Ito K, Bernardi R et al.PML targeting eradicates quiescent leukaemia-initiating cells. Nature. 2008 Jun 19;453:1072-8. 

30.     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.  

31.     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.

32.     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.

33.     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.        Morganti C, Bonora M, Ito K. Metabolism and HSC fate: what NADPH is made for. Trends Cell Biol. 2024 Jul 24:S0962-8924(24)00141-7. PMID: 39054107

2.        Torres LS, Asada N, Weiss MJ, Trumpp A, Suda T, Scadden DT, Ito K. Recent advances in “Sickle and Niche” research - Tribute to Dr. Paul S Frenette. Stem Cell Reports. 2022 Jul 12;17(7):1509-1535. PMID: 35830837.

3.        Morganti C, Cabezas-Wallscheid D, Ito K. Metabolic Regulation of Hematopoietic Stem Cells. Hemasphere. 2022 Jun 28;6(7):e740. PMID: 35785147 PMCID: PMC9242402.

4.        Maryanovich M, Ito K. CD36-mediated fatty acid oxidation in hematopoietic stem cells is a novel mechanism of emergency hematopoiesis in response to infection. Immunometabolism. 2022;4(2):e220008. PMID: 35465142 PMCID: PMC9029143.

5.        Ito K, Ito K. Leukemia stem cells as a potential target to achieve therapy-free remission in chronic myeloid leukemia. Cancers. 2021 Nov 20;13(22):5822.

6.        Morganti C, Ito K. Mitochondrial Contributions to Hematopoietic Stem Cell Aging. Int J Mol Sci. 2021 Oct 15;22(20):11117. doi: 10.3390/ijms222011117

7.        Nakamura-Ishizu A, Ito K, Suda T. Hematopoietic stem cell metabolism during development and aging. Dev Cell. 2020 Jul;54(2):239-255.

8.        Ito K, Bonora M, Ito K. Metabolism as master of hematopoietic stem cell fate. Int J Hematol. 2019 Jan;109(1):18-27.

9.        Ito K, Ito K. Hematopoietic stem cell fate through metabolic control. Exp Hematol. 2018 Aug;64:1-11. 

10.     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.

11.     Ito K*, Frenette PS*. HSC Contribution in Making Steady-State Blood. Immunity. 2016. Sep 20;45(3):464.

12.     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. 

13.     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. 

14.     Ito K, Ito K. Resistance in the Ribosome: RUNX1, pre-LSCs, and HSPCs. Cell Stem Cell. 2015 Aug 6;17(2):129-31. 

15.     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.)

16.     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. 

17.     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. 

18.     Weiss CN, Ito K. DNA damage response, redox status and hematopoiesis. Blood Cells Mol Dis. 2014 Jan;52(1):12-8. 

19.     Ito K, Ito K. Newly Identified Roles of PML in Stem Cell Biology. Front Oncol. 2013 Mar 14;3:50.  

20.     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 (Book chapters)

1.        Mochizuki-Kashio M, Ito K*, Nakamura-Ishizu A*. Mitochondrial and lysosomal metabolism in hematopoietic stem cells. Encyclopedia of Cell Biology. in press

2.        Ito K, Ito K. Normal Hematopoiesis and Blood Cells, Maturation. Hoffman’s Atlas of Diagnostic Hematology. Oct 2020:1-12.

3.        Ito K, Ito K. Growth Factors. Hoffman’s Atlas of Diagnostic Hematology. Oct 2020:13-21.

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

Organized Research Topic

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

      Metabolic control in hematopoietic homeostasis. Exp Hematol. Dec 2023 (Topic Editor: Ito K)

In Memoriam

·         Cell Leading Edge. Paul S. Frenette (1965-2021). Bowman TV et al. 2021 Sep 30;184(20):5073-5076.  Cell Stem Cell  Dev Cell         

·         Stem Cell Reports Review. Torres LS et al. 2022 Jul 12;17(7):1509-1535.

·         FASEB BioAdvances Special Issue: Neuroscience of Cancer, Regeneration, and Immunity. Tribute Paul S. Frenette (1965-2021). Ito K, Bowman T. 2022 Jan;4(1):5-8.   

·         ASH News and Report. Of Nestin and Niches: Paul S. Frenette, MD. Daily J, Ito K, Billett HH. The Hematologist 2021;18 (5).

·         ISEH Simply blood. In Memory of Paul Sylvain Frenette

·         Einstein. Remembering Paul S. Frenette, M.D. (Features)

·         Experimental Hematology. In Memoriam: Prof. Makio Ogawa. Ito K et al. in press.

Research Support

NIH     1. Lipid metabolism in the maintenance of HSCs

            2. Tet2's role in HSCs and hematologic disorders

            3. To understand how nociceptors inhibit SCD-associated vaso-occlusion

LLS     1. Dissecting mitochondrial alterations to the pathogenesis of myelodysplastic syndrome

Shared Facilities: Director and Faculty Supervisor, Single Cell Genomics Core 

Training Program: The New York Consortium for Interdisciplinary Training in Kidney, Urological, & Hematological Research (NYTrainKUHR)

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

• 2022      Paul S. Frenette Memorial Symposium    
• 2020      4^th Stem Cell Symposium
• 2018      2^nd Einstein Stem Cell Institute Retreat
• 2017      3^rd Stem Cell Symposium
• 2015      1^st Einstein Stem Cell Institute Retreat