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Article
Open AccessDDX41 haploinsufficiency causes inefficient hematopoiesis under stress and cooperates with p53 mutations to cause hematologic malignancy
Germline heterozygous mutations in DDX41 predispose individuals to hematologic malignancies in adulthood. Most of these DDX41 mutations result in a truncated protein, leading to loss of protein function. To in...
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Article
Open AccessMetabolic reprogramming regulated by TRAF6 contributes to the leukemia progression
TNF receptor associated factor 6 (TRAF6) is an E3 ubiquitin ligase that has been implicated in myeloid malignancies. Although altered TRAF6 expression is observed in human acute myeloid leukemia (AML), its rol...
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Article
Runx1/3-driven adaptive endoplasmic reticulum stress pathways contribute to neurofibromagenesis
Neurofibromatosis type 1 (NF1) patients are predisposed to develop plexiform neurofibromas (PNFs). Three endoplasmic reticulum (ER) stress response pathways restore cellular homeostasis. The unfolded protein r...
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Article
Open AccessThe deubiquitinase USP15 modulates cellular redox and is a therapeutic target in acute myeloid leukemia
Ubiquitin-specific peptidase 15 (USP15) is a deubiquitinating enzyme implicated in critical cellular and oncogenic processes. We report that USP15 mRNA and protein are overexpressed in human acute myeloid leuk...
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Article
WNT5A inhibition alters the malignant peripheral nerve sheath tumor microenvironment and enhances tumor growth
Malignant peripheral nerve sheath tumors (MPNST) are aggressive soft-tissue sarcomas that cause significant mortality in adults with neurofibromatosis type 1. We compared gene expression of growth factors in n...
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Article
MicroRNA-155 contributes to plexiform neurofibroma growth downstream of MEK
MicroRNAs (miRs) are small non-coding RNAs that can have large impacts on oncogenic pathways. Possible functions of dysregulated miRs have not been studied in neurofibromatosis type 1 (NF1) plexiform neurofibr...
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Article
Adaptive response to inflammation contributes to sustained myelopoiesis and confers a competitive advantage in myelodysplastic syndrome HSCs
Despite evidence of chronic inflammation in myelodysplastic syndrome (MDS) and cell-intrinsic dysregulation of Toll-like receptor (TLR) signaling in MDS hematopoietic stem and progenitor cells (HSPCs), the mec...
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Article
NF1 patient missense variants predict a role for ATM in modifying neurofibroma initiation
In Neurofibromatosis type 1, NF1 gene mutations in Schwann cells (SC) drive benign plexiform neurofibroma (PNF), and no additional SC changes explain patient-to-patient variability in tumor number. Evidence from ...
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Article
U2AF1 mutations induce oncogenic IRAK4 isoforms and activate innate immune pathways in myeloid malignancies
Spliceosome mutations are common in myelodysplastic syndromes (MDS) and acute myeloid leukaemia (AML), but the oncogenic changes due to these mutations have not been identified. Here a global analysis of exon ...
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Article
STAT3 inhibition reduces macrophage number and tumor growth in neurofibroma
Plexiform neurofibroma, a benign peripheral nerve tumor, is associated with the biallelic loss of function of the NF1 tumor suppressor in Schwann cells. Here, we show that FLLL32, a small molecule inhibitor of JA...
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Article
Open AccessiGEAK: an interactive gene expression analysis kit for seamless workflow using the R/shiny platform
The use of microarrays and RNA-seq technologies is ubiquitous for transcriptome analyses in modern biology. With proper analysis tools, the differential gene expression analysis process can be significantly ac...
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Article
Open AccessDefective transcription elongation in a subset of cancers confers immunotherapy resistance
The nature and role of global transcriptional deregulations in cancers are not fully understood. We report that a large proportion of cancers have widespread defects in mRNA transcription elongation (TE). Canc...
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Article
Open AccessHepatic Ago2-mediated RNA silencing controls energy metabolism linked to AMPK activation and obesity-associated pathophysiology
RNA silencing inhibits mRNA translation. While mRNA translation accounts for the majority of cellular energy expenditure, it is unclear if RNA silencing regulates energy homeostasis. Here, we report that hepat...
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Article
Open AccessLoss of NR2E3 represses AHR by LSD1 reprogramming, is associated with poor prognosis in liver cancer
The aryl hydrocarbon receptor (AHR) plays crucial roles in inflammation, metabolic disorder, and cancer. However, the molecular mechanisms regulating AHR expression remain unknown. Here, we found that an orpha...
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Article
Correction: Corrigendum: Ubiquitination of hnRNPA1 by TRAF6 links chronic innate immune signaling with myelodysplasia
Nat. Immunol. 18, 236–245; published online 26 December 2016; corrected after print 23 January 2017 In the version of this article initially published online, the 16th author's surname was spelled incorrectly ...
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Article
Open AccessAn inflammatory gene signature distinguishes neurofibroma Schwann cells and macrophages from cells in the normal peripheral nervous system
Neurofibromas are benign peripheral nerve tumors driven by NF1 loss in Schwann cells (SCs). Macrophages are abundant in neurofibromas, and macrophage targeted interventions may have therapeutic potential in these...
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Article
Ubiquitination of hnRNPA1 by TRAF6 links chronic innate immune signaling with myelodysplasia
Starczynowski and colleagues show that overexpression of TRAF6 in HSCs induces ubiquitination of the RNA-binding protein hnRNPA1 and alternative splicing of Arhgap1, which accounts for the hematopoietic defect...
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Mechanical Properties of Aluminium-Based Nanocomposite Reinforced with Fullerenes
Aluminum has been spot-lighted due to its earth-abundant and light-weight nature. However, usages of aluminum as an engineering material have been limited by its low strength compared to other engineering meta...
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Article
A Slee** Beauty forward genetic screen identifies new genes and pathways driving osteosarcoma development and metastasis
Branden Moriarity, David Largaespada and colleagues report a Slee** Beauty forward genetic screen in mice that identifies candidate genes and pathways for osteosarcoma tumor development and progression. They id...
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Article
Forward genetic screen for malignant peripheral nerve sheath tumor formation identifies new genes and pathways driving tumorigenesis
Eric Rahrmann and colleagues performed a transposon-based somatic mutagenesis screen for genes involved in malignant peripheral nerve sheath tumors (MPNSTs). They identified many recurrent transposon insertion...
