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Jiang, Hao

Hao Jiang

Primary Appointment

Biochemistry and Molecular Genetics

Contact Information

Email: hj8d@virginia.edu

Research Interests

Regulation of stem cell function and tumorigenicity by epigenetic and novel biophysical mechanisms

Research Description

The broad interest of the Jiang lab is how gene regulation at the chromatin, transcriptional, and post-transcriptional levels controls the stability and plasticity of cell identity, how dysregulation of these mechanisms lead to diseases especially cancer, and how we may develop novel molecules to combat these diseases based on these mechanisms. We are studying the functional role of efficient H3K4 methylation in regulating stem cell fate determination and tumorigenesis. We have shown that Dpy30, one of the core subunits in the Set1/Mll family of H3K4 methyltransferases, plays an important role in the fate determination of embryonic (Jiang et al, Cell 2011) and hematopoietic (Yang et al., Blood 2014; Yang et al., J Exp Med 2016) stem cells. Moreover, our recent studies using our genetically engineered mouse model strongly suggest that cancer cells hijack this epigenetic modulator to drive a gene expression program supporting tumorigenesis, meanwhile creating ?epigenetic vulnerability?. We are currently studying the molecular mechanisms underlying such epigenetic vulnerability and also developing pharmacologic intervention strategies to target this modulator for potential cancer treatment. It remains largely unclear how gene expression is spatiotemporally regulated in cells and how such spatiotemporal control of gene expression impacts physiological and pathological processes. AKAP95 is associated with several human diseases including cancer, but the molecular activities of AKAP95 are poorly defined. Our previous work (Jiang et al., Nat Struct Mol Biol 2013) has identified AKAP95 as a remarkable transcription co-activator. We have recently shown that, surprisingly, AKAP95 is an RNA-binding protein and regulates alternative pre-mRNA splicing by direct interaction with pre-mRNA and hnRNP proteins (Hu et al., Nat Comm 2016). We have recently started to study a novel biophysical mechanism by which AKAP95 and related factors spatiotemporally regulate transcription and splicing to control animal development and diseases. Currently, our research is funded by the NIH, American Society of Hematology, American Cancer Society, and Leukemia & Lymphoma Society.

Selected Publications

Yang Z, Shah K, Khodadadi-Jamayran A, Jiang H, Control of Hematopoietic Stem Cell Function Through Epigenetic Regulation of Energy Metabolism and Genome Integrity, ; Stem Cell Reports. 13() |

Shah K, Whitaker R, Busby T, Hu J, Shi B, Wang Z, Zang C, Placzek W, Jiang H, Specific inhibition of DPY30 activity by ASH2L-derived peptides suppresses blood cancer cell growth, ; Experimental Cell Research. 0() |

Li W, Hu J, Shi B, Jiang H, Protein condensates with appropriate material properties regulate tumorigenesis, ; BioRxiv 536839 . () |

Shah K, King GD, Jiang H, A chromatin modulator sustains self-renewal and enables differentiation of postnatal neural stem and progenitor cells., 2019; Journal of molecular cell biology. () PMID: 31065682 |

Yang Zhenhua, Shah Kushani, Busby Theodore, Giles Keith, Khodadadi-Jamayran Alireza, Li Wei, Jiang Hao, Hijacking a key chromatin modulator creates epigenetic vulnerability for Myc-driven cancer, ; Journal of Clinical Investigation, In press. () |

Yang Z, Shah K, Busby T, Giles K, Khodadadi-Jamayran A, Li W, Jiang H, Hijacking a key chromatin modulator creates epigenetic vulnerability for Myc-driven cancer., 2018; The Journal of clinical investigation. () PMID: 29870403 |

Hu J, Khodadadi-Jamayran A, Mao M, Shah K, Yang Z, Nasim MT, Wang Z, Jiang H, AKAP95 regulates splicing through scaffolding RNAs and RNA processing factors., 2016; Nature communications. 7() 13347 PMID: 27824034 | PMCID: PMC5105168

Yang Z, Shah K, Khodadadi-Jamayran A, Jiang H, Dpy30 is critical for maintaining the identity and function of adult hematopoietic stem cells., 2016; The Journal of experimental medicine. 213(11) 2349-2364 PMID: 27647347 | PMCID: PMC5068233

Yang Z, Augustin J, Hu J, Jiang H, Physical Interactions and Functional Coordination between the Core Subunits of Set1/Mll Complexes and the Reprogramming Factors., 2015; PloS one. 10(12) e0145336 PMID: 26691508 | PMCID: PMC4686221

Yang Z, Augustin J, Chang C, Hu J, Shah K, Chang CW, Townes T, Jiang H, The DPY30 subunit in SET1/MLL complexes regulates the proliferation and differentiation of hematopoietic progenitor cells., 2014; Blood. 124(13) 2025-33 PMID: 25139354 | PMCID: PMC4507038

Jiang H, Lu X, Shimada M, Dou Y, Tang Z, Roeder RG, Regulation of transcription by the MLL2 complex and MLL complex-associated AKAP95., 2013; Nature structural & molecular biology. 20(10) 1156-63 PMID: 23995757 | PMCID: PMC3813012

Jiang H, Shukla A, Wang X, Chen WY, Bernstein BE, Roeder RG, Role for Dpy-30 in ES cell-fate specification by regulation of H3K4 methylation within bivalent domains., 2011; Cell. 144(4) 513-25 PMID: 21335234 | PMCID: PMC3572774

Jiang H, Chang FC, Ross AE, Lee J, Nakayama K, Nakayama K, Desiderio S, Ubiquitylation of RAG-2 by Skp2-SCF links destruction of the V(D)J recombinase to the cell cycle., 2005; Molecular cell. 18(6) 699-709 PMID: 15949444 |

Jiang H, Ross AE, Desiderio S, Cell cycle-dependent accumulation in vivo of transposition-competent complexes between recombination signal ends and full-length RAG proteins., 2003; The Journal of biological chemistry. 279(9) 8478-86 PMID: 14660558 |

Shah K, King G, Jiang H, A chromatin modulator sustains self-renewal and enables differentiation of postnatal neural stem and progenitor cells, ; Journal of Molecular Cell Biology. () |