Nan Zhu, PhD
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.
- NCI R37 MERIT Award for Early Stage Investigators "The Histone Demethylase JMJD1C in Human Acute Myeloid Leukemia," 2019 - 2024, Role: PI
Theresa Bluemn, PhD
- Bluemn T, Schmitz J, Chen Y, Zheng Y, Zhang Y, Zheng S, Burns R, DeJong J, Christiansen L, Izaguirre-Carbonell J, Wang D and Zhu N*. Arid2 regulates HSC differentiation in normal hematopoiesis. Exp Hematol. 2021 Feb;94:37-46. doi: 10.1016/j.exphem.2020.12.004. Epub 2020 Dec 17.PMID: 33346030. * Corresponding author
- 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. *Corresponding author
- 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
- 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
- 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. * Corresponding author
- 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
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