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Nan Zhu, PhD

Nan Zhu, PhD

Associate Investigator

Education and Training

Postdoctoral Training
Memorial Sloan Kettering Cancer Center, New York, NY
Brigham and Women's Hospital and Children's Hospital, Boston, MA

Doctoral Training
Boston University, Boston, MA

Contact Us

Nan Zhu, PhD

Associate Investigator
Email (414) 937-6835

  • Research Interests

    My laboratory studies the epigenetic regulation of stem cells and how dysregulation of these pathways contributes to cancer development. Epigenetic mechanisms play an important role in maintaining tissue-specific gene expression patterns and are essential for normal development processes such as hematopoiesis. In normal blood cell development, hematopoietic stem cell (HSC) sits at the top of a hierarchy and has the unique ability to self-renew and differentiate into all blood lineages. HSC self-renewal is tightly controlled and epigenetic regulators play critical roles in this process. In leukemia, cancer cells often harbor multiple genetic mutations that enable them to acquire aberrant self-renewal ability. Recent sequencing of human cancer genome has revealed that mutations in epigenetic regulators commonly occur in leukemia, highlighting their importance in malignancy.  

    We are interested in understanding the epigenetic regulation of normal and malignant hematopoiesis. We approach this by studying the role of epigenetic regulators in normal and malignant hematopoietic stem cell function. The model systems we use include murine and in vitro model systems. We use techniques such as standard biochemical assays, multi-parameter flow cytometry and genomic and transcriptome profiling by next generation sequencing. We are actively investigating epigenetic factors implicated in acute myeloid leukemia (AML) biology as well as epigenetic regulation of key transcription factors in hematopoiesis. 

  • Grant Support
    • NCI R37 MERIT Award for Early Stage Investigators "The Histone Demethylase JMJD1C in Human Acute Myeloid Leukemia,"  2019 - 2024, Role: PI
    • ASH Scholar Award, "Understanding Molecular Mechanism of JMJD1C Function in AML," 2018 - 2019, Role: PI
    • R. Douglas Ziegler Innovation Award "CRISPR/Cas9 Screen to Identify Driver Non-coding Variants in AML Leukemogenesis," 2019, Role: PI
  • Lab

    Jesus Izaguirre Carbonell
    Postdoctoral Fellow

    Jesse Schmitz
    Assistant Research Technologist

    Luke Christiansen
    Graduate Student

    Theresa Bluemn
    Graduate Student

  • Publications
    1. Izaguirre-Carbonell J, Christiansen L, Burns R, Schmitz J, Li C, Mokry RL, Bluemn T, Zheng Y, Shen J, Carlson KS, Rao S, Wang D, Zhu N. Critical role of Jumonji domain of JMJD1C in MLL-rearranged leukemia. Blood Adv. 2019 May 14; 3(9):1499-1511. PMID: 31076406.
    2. Yu M, Chen Y, Zeng H, Zheng Y, Fu G, Zhu W, Broeckel U, Aggarwal P, Turner A, Neale G, Guy C, Zhu N, Chi H, Wen R, Wang D. PLCγ-dependent mTOR signalling controls IL-7-mediated early B cell development. Nat Commun. 2017 Nov 13; 8(1):1457. PMID: 29133930.
    3. Olp MD, Zhu N, Smith BC. Metabolically Derived Lysine Acylations and Neighboring Modifications Tune the Binding of the BET Bromodomains to Histone H4. Biochemistry. 2017 Oct 17; 56(41): 5485-5495. PMID: 28945351.
    4. Danis E, Yamauchi T, Echanique K, Zhang X, Haladyna JN, Riedel SS, Zhu N, Xie H, Orkin SH, Armstrong SA, Bernt KM, Neff T. Ezh2 Controls an Early Hematopoietic Program and Growth and Survival Signaling in Early T Cell Precursor Acute Lymphoblastic Leukemia. Cell Rep. 2016 Mar 1; 14(8):1953-65. PMID:26904942
    5. Zhu N, Chen M, Eng R, DeJong J, Sinha AU, Rahnamay NF, Koche R, Al-Shahrour F, Minehart JC, Chen CW, Deshpande AJ, Xu H, Chu SH, Ebert BL, Roeder RG, Armstrong SA. MLL-AF9- and HOXA9-mediated acute myeloid leukemia stem cell self-renewal requires JMJD1C. J Clin Invest. 2016 Mar 1; 126(3):997-1011. PMID: 26878175
    6. Danis E, Yamauchi T, Echanique K, Haladyna J, Kalkur R, Riedel S, Zhu N, Xie H, Bernt KM, Orkin SH, Armstrong SA, Neff T. Inactivation of Eed impedes MLL-AF9-mediated leukemogenesis through Cdkn2a-dependent and Cdkn2a-independent mechanisms in a murine model. Exp Hematol. 2015 Nov; 43(11):930-935.e6. PMID:26118502
    7. Chen M, Zhu N, Liu X, Laurent B, Tang Z, Eng R, Shi Y, Armstrong SA, Roeder RG. JMJD1C is required for the survival of acute myeloid leukemia by functioning as a coactivator for key transcription factors. Genes Dev. 2015 Oct 15; 29(20):2123-39. PMID: 26494788
    8. Chen CW, Koche RP, Sinha AU, Deshpande AJ, Zhu N, Eng R, Doench JG, Xu H, Chu SH, Qi J, Wang X, Delaney C, Bernt KM, Root DE, Hahn WC, Bradner JE, Armstrong SA. DOT1L inhibits SIRT1-mediated epigenetic silencing to maintain leukemic gene expression in MLL-rearranged leukemia. Nature medicine. 2015 Apr; 21(4):335-43. PMID: 25822366   
    9. Deshpande, A.J., Deshpande A.A., Sinha A.U., Chen L., Chang J., Cihan A., Fazio M., Chen C., Zhu N., Koche, R., Dzhekieva, L., Ibáñez G., , Dias S., Banka D., Krivtsov A., Luo, M., Roeder R.G., Bradner J.E., Bernt K.M., Armstrong S. A. AF10 Regulates Progressive H3K79 Methylation and Hox Gene Expression in Diverse AML Subtypes. Cancer Cell, 2014 Dec 8; 26(6):p.896-908. PMID: 25464900   
    10. Huang, C. H., Lujambio, A., Zuber, J., Tschaharganeh, D. F., Doran, M. G., Evans, M. J., Kitzing, T., Zhu, N., de Stanchina, E., Sawyers, C. L., Armstrong S.A., Lewis, J.S., Sherr, C.J., Lowe, S.W. CDK9-mediated transcription elongation is required for MYC addiction in hepatocellular carcinoma. Genes Dev. 2014 Aug 15; 28(16): 1800-1814. PMID: 25128497
    11. Lobry C, Ntziachristos P, Ndiaye-Lobry D, Oh P, Cimmino L, Zhu N, Araldi E, Hu W, Freund J, Abdel-Wahab O, Ibrahim S, Skokos D, Armstrong SA, Levine RL, Park CY, Aifantis I. Notch pathway activation targets AML-initiating cell homeostasis and differentiation. J Exp Med. 2013 Feb 11; 210(2):301-19. PMID:23359070
    12. Tam WF, Hähnel PS, Schüler A, Benjamin LH, Okabe R, Zhu N, Pante S, Raffel G, Mercher T, Wernig G, Bockamp E, Sasca D, Kreft A, Robinson GW, Hennighausen L, Gilliland DG, Kindler T. STAT5 is crucial to maintain leukemic stem cells in acute myeloid leukemias induced by MOZ-TIF2. Cancer Res. 2013 Jan 1;73(1):373-84.PMID: 23149921
    13. Liu J, Mercher T, Scholl C, Brumme C, Gilliland DG,  Zhu N. A Functional role for the histone demethylase UTX in normal and malignant hematopoietic cells. Exp Hematol. 2012 Jun; 40(6):487-498. PMID: 22306297
    14. Neff T, Sinha AU, Kluk MJ, Zhu N, Khattab MH, Stein L, Xie H, Orkin SH,  Armstrong SA. Polycomb repressive complex 2 is required for MLL-AF9 Leukemia. Proc Natl Acad Sci. 2012 Mar 27;109(13):5028-33. PMID: 22396593
    15. Onder TT, Kara N, Cherry A, Sinha AU, Zhu N, Bernt KM, Cahan P, Mancarci OB, Unternaehrer J, Gupta PB, Lander ES, Armstrong SA, Daley GQ. Chromatin modifying enzymes as barriers or facilitators of reprogramming. Nature. 2012 Mar 4; 483(7391):598-602. PMID: 22388813
    16. Trowbridge JJ, Sinha AU, Zhu N, Li M, Armstrong SA and Orkin SH. Haploinsufficiency of Dnmt1 impairs leukemia stem cell function through derepression of bivalent chromatin domains. Genes Dev. 2012 Feb 15; 26(4):344-9. PMID: 22345515
    17. Bernt KM*, Zhu N*, Sinha AU*, Vempati S, Faber J, Krivtsov AV, Feng Z, Punt N, Daigle A, Bullinger L, Pollock RM, Richon VM, Kung AL, Armstrong SA. MLL-rearranged leukemia is dependent on aberrant H3K79 methylation by DOT1L. Cancer Cell. 2011 Jul 12; 20(1):66-78. (*equal contribution) PMID:21741597
    18. Zhu N, Hansen U. Transcriptional regulation by HMGN proteins. Biochim Biophys Acta. 2010 Jan-Feb; 1799(1-2):74-9. Review. PMID:20123070
    19. Zhu N, Hansen U. HMGN1 modulates estrogen-mediated transcriptional activation through interactions with specific DNA-binding transcription factors. Mol Cell Biol. 2007 Dec; 27(24):8859-73 PMID:17938209
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