2017-04-07A recent study shows that a self-peptide generated in pancreatic islet beta cells through the translation of a noncanonical alternative reading frame in human insulin mRNA is recognized by both CD4+ and CD8+ T cells in type 1 diabetes.
2017-04-07In a recent study, researchers generated a mouse model expressing variant APOL1 that recapitulates human kidney disease. Variant APOL1 leads to caspase-1-dependent pyroptosis, which opens the door for the development of new druggable targets to treat APOL1-mediated kidney disease.
2017-04-07New studies advance the mechanistic understanding of mutant histone H3 in diffuse intrinsic pontine glioma (DIPG) and demonstrate two epigenetic approaches, BET inhibition and EZH2 inhibition, as potential therapeutic strategies for DIPG.
2017-04-03In this Review, Cathomen and colleagues present the latest advances, including improvements in nuclease specificity and delivery, that will expedite the clinical translation of genome editing.
2017-03-06Glucocorticoid treatment of human cord blood hematopoietic stem cells increases expression of the receptor CXCR4 by chromatin remodeling, thereby enhancing hematopoietic stem cell homing and engraftment.
2017-02-20Risk variants of APOL1 associated with human chronic kidney disease have been identified, but causality has been unclear. Transgenic expression in mice now shows that such alleles can indeed cause renal disease.
2017-02-20Targeting CFLAR in mouse and non-human primates ameliorates non-alcoholic steatohepatitis by decreasing JNK signaling in hepatocytes.
2017-03-13The G-protein-coupled receptor GPR124, acting through the canonical Wnt pathway, is required for the maintenance of blood–brain barrier function in mouse models of stroke and glioblastoma.
2017-02-27Whereas cisplatin and carboplatin kill cancer cells by inducing DNA damage, another platinum derivative, oxaliplatin, induces cell death by triggering ribosome biogenesis stress.
2017-03-20The intrinsic resistance of BCR-ABL-expressing chronic myeloid leukemia stem cells to treatment with tyrosine-kinase inhibitors requires growth-factor signaling through the proteins c-Fos and DUSP1. Combined inhibition of BCR-ABL, c-Fos, and DUSP1 eradicated leukemia in vivo, pointing to a new therapeutic strategy for kinase-driven leukemias.
2017-02-27Although mutant H3K27M histones inhibit PRC2 in diffuse intrinsic pontine gliomas, these tumors exhibit significant amounts of PRC2 activity. The repression of several genes, including INK4A, by residual EZH2 activity is required for tumor growth, and EZH2 inhibitors therefore represent potential therapies for these patients.
2017-02-27Nucleosomes containing mutant K27M histones in diffuse intrinsic pediatric gliomas (DIPG) exclude PRC2 binding and recruit BET bromodomain proteins; however, residual PRC2-dependent repression of specific loci, is required for DIPG oncogenesis. These results provide a rationale for targeting these epigenetic regulators in patients.
2017-02-27Use of an alternative open reading frame, potentially as a result of cellular stress, drives production of an unconventional insulin epitope that is recognized by cytotoxic T cells from individuals with type 1 diabetes; these T cells kill beta cells in vitro.
2017-02-27Selenoprotein P is released from the liver and acts through LRP1 in the muscle to contribute to exercise resistance in mouse and man by inhibiting ROS levels via inhibition of AMPK and PGC-1α.
2017-03-13HRDetect represents a model integrating whole-genome sequencing mutation signatures associated with BRCA1 and BRCA2 deficiency. The implementation of this predictor across different tumor types identifies a larger proportion of patients displaying ‘BRCAness’ than previously recognized; they might derive benefit from platinum and PARP-inhibitor therapies.