George F Murphy

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Advancing the understanding of human and experimental disease

Latest Research

  • Article |

    The authors profiled differentially expressed microRNAs between parental adherent breast cancer cells and breast cancer stem cell (BCSC) -mimicking mammospheres, and identified hsa-miR-27a as a negative regulator for survival and chemoresistance of BCSCs by downregulating genes essential for detoxification of ROS and impairing of autophagy. Enhancement of the hsa-miR-27a signaling pathway may be a potential therapeutic modality for breast cancer.

    • Shinobu Ueda
    • , Masakatsu Takanashi
    • , Katsuko Sudo
    • , Kohsuke Kanekura
    •  & Masahiko Kuroda
  • Article |

    WFS1 is a causative gene for Wolfram syndrome, a rare neurodegenerative disorder characterized by juvenile-onset diabetes mellitus and optic nerve atrophy. Genetic proof of concept studies coupled with RNA-seq reveal that increasing WFS1 confers a survival advantage to cells under ER stress by activating Akt pathways and preserving ER homeostasis. This work reveals essential pathways regulated by WFS1 and therapeutic targets for Wolfram syndrome.

    • Damien Abreu
    • , Rie Asada
    • , John M. P. Revilla
    • , Zeno Lavagnino
    • , Kelly Kries
    • , David W. Piston
    •  & Fumihiko Urano
  • Technical Report |

    Gene δ-sarcoglycan was knocked out in pigs via gene editing and somatic cell cloning. Loss of expression led to α-, β-, and γ-sarcoglycan depletion in the cardiac and skeletal sarcolemma. Pigs exhibiting systolic dysfunction, myocardial tissue degeneration, and sudden death are promising for studying next-generation therapies for human genetic cardiomyopathy.

    • Hitomi Matsunari
    • , Michiyo Honda
    • , Masahito Watanabe
    • , Satsuki Fukushima
    • , Kouta Suzuki
    • , Shigeru Miyagawa
    • , Kazuaki Nakano
    • , Kazuhiro Umeyama
    • , Ayuko Uchikura
    • , Kazutoshi Okamoto
    • , Masaki Nagaya
    • , Teruhiko Toyo-oka
    • , Yoshiki Sawa
    •  & Hiroshi Nagashima
  • Article
    | Open Access

    Generation of peptide fragments by oxidation of hemoglobin to ferryl hemoglobin occurs in ruptured atherosclerotic lesion in human and in intraventricular hemorrhage of brain in preterm infants. Peptide fragments of hemoglobin provoke intercellular gap formation and enhance monocyte adhesion to endothelial cell. Activation of endothelium via NF-κβ leads to TNF and IL-1β production, induction of NLRP3 and CASP1.

    • Niké Posta
    • , Éva Csősz
    • , Melinda Oros
    • , Dávid Pethő
    • , László Potor
    • , Gergő Kalló
    • , Zoltán Hendrik
    • , Katalin Éva Sikura
    • , Gábor Méhes
    • , Csaba Tóth
    • , József Posta
    • , György Balla
    •  & József Balla
  • Article |

    This study demonstrates that ablation of the l-histidine decarboxylase /histamine axis using a genetically modified mouse model ameliorates liver damage and hepatic fibrosis. Further, histamine reactivates the axis via H1/H2 receptors, thus recapitulating the liver damage and fibrosis of primary sclerosing cholangitis. Histamine regulation of TGF-β1 and VEGF-C may be targeted therapies for this disease.

    • Lindsey Kennedy
    • , Vik Meadows
    • , Jennifer Demieville
    • , Laura Hargrove
    • , Shohaib Virani
    • , Shannon Glaser
    • , Tianhao Zhou
    • , Evan Rinehart
    • , Victoria Jaeger
    • , Konstantina Kyritsi
    • , Linh Pham
    • , Gianfranco Alpini
    •  & Heather Francis
  • Article |

    Changes in DNA methylation contribute to the pathogenesis of cardiovascular disease, including dilated cardiomyopathy and heart failure, by regulating gene expression. The authors show that DNA methyltransferase 1 deficiency in the myocardium restricts the reprogramming of genes and activates pathways involved in myocardial protection and apoptosis in response to pathological stress.

    • Tong-Tong Wu
    • , Yuan-Wu Ma
    • , Xu Zhang
    • , Wei Dong
    • , Shan Gao
    • , Ji-Zheng Wang
    • , Lian-Feng Zhang
    •  & Dan Lu

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