Frederic Cantin, Labonté Lab.

Inflammatory illness: Why the next wave of antidepressants may target the immune system

Latest Research

  • Letter |

    The N6-methyladenosine (m6A) modification in mRNAs, generated by the enzyme METTL3, controls normal human hematopoietic stem/progenitor cell differentiation and maintains the undifferentiated leukemic phenotype of human acute myeloid leukemia cells.

    • Ly P Vu
    • , Brian F Pickering
    • , Yuanming Cheng
    • , Sara Zaccara
    • , Diu Nguyen
    • , Gerard Minuesa
    • , Timothy Chou
    • , Arthur Chow
    • , Yogesh Saletore
    • , Matthew MacKay
    • , Jessica Schulman
    • , Christopher Famulare
    • , Minal Patel
    • , Virginia M Klimek
    • , Francine E Garrett-Bakelman
    • , Ari Melnick
    • , Martin Carroll
    • , Christopher E Mason
    • , Samie R Jaffrey
    •  & Michael G Kharas
  • Article |

    A silent single-nucleotide variant (SNV) affecting the transcription of a long noncoding RNA (lncRNA EGFR-AS1) within the EGFR coding region alters the EGFR isoform ratio and modulates oncogene addiction and response to EGFR tyrosine kinase inhibitors in squamous-cell cancers. Proof-of-concept validation in patients supports the notion that this SNV and levels of the lncRNA could be used to predict response to therapy in a clinical setting. These results, together with findings by Bal et al., uncover the functional role of noncoding RNAs in modulating the response to targeted therapies in cancer.

    • Daniel S W Tan
    • , Fui Teen Chong
    • , Hui Sun Leong
    • , Shen Yon Toh
    • , Dawn P Lau
    • , Xue Lin Kwang
    • , Xiaoqian Zhang
    • , Gopinath M Sundaram
    • , Gek San Tan
    • , Mei Mei Chang
    • , Boon Tin Chua
    • , Wan Teck Lim
    • , Eng Huat Tan
    • , Mei Kim Ang
    • , Tony K H Lim
    • , Prabha Sampath
    • , Balram Chowbay
    • , Anders J Skanderup
    • , Ramanuj DasGupta
    •  & N Gopalakrishna Iyer
  • Article |

    Factors secreted by metastatic a primary tumors induce an early phenotypic switch in perivascular cells at distant pre-metastatic niches. By using sophisticated lineage-tracing mouse models, the authors demonstrate that enhanced KLF4 expression in these cells increases their ability to proliferate and migrate away from the vasculature, and augments fibronectin deposition, which contributes to metastatic growth. These findings increase the mechanistic understanding of the metastatic process and uncover a role for perivascular plasticity that could be targeted to prevent metastasis.

    • Meera Murgai
    • , Wei Ju
    • , Matthew Eason
    • , Jessica Kline
    • , Daniel W Beury
    • , Sabina Kaczanowska
    • , Markku M Miettinen
    • , Michael Kruhlak
    • , Haiyan Lei
    • , Jack F Shern
    • , Olga A Cherepanova
    • , Gary K Owens
    •  & Rosandra N Kaplan
  • Letter |

    Treatment with tyrosine kinase inhibitors results in a survival benefit in patients with chronic myeloid leukemia (CML). However, relapse due to persistent leukemic stem cells (LSCs) requires additional selective targets for efficient eradication of the disease. Metabolomic analyses on patient-derived CML LSCs reveal that these have an increased dependency on oxidative metabolism that renders them sensitive to treatment with tigecycline, an FDA-approved inhibitor of mitochondrial translation. These findings uncover a new metabolic vulnerability in CML and provide a rational approach for further clinical evaluation.

    • Elodie M Kuntz
    • , Pablo Baquero
    • , Alison M Michie
    • , Karen Dunn
    • , Saverio Tardito
    • , Tessa L Holyoake
    • , G Vignir Helgason
    •  & Eyal Gottlieb
  • Letter |

    John Harty and colleagues report that, in mouse models of malaria, regulatory T cells expand, as in humans, and inhibit conventional T cells and germinal center B cells, thereby impairing protective responses against blood-stage disease. Timed blockade of the inhibitory receptor CTLA-4 cured infection in mice and promoted cross-protective blood-stage immunity against a different Plasmodium species.

    • Samarchith P Kurup
    • , Nyamekye Obeng-Adjei
    • , Scott M Anthony
    • , Boubacar Traore
    • , Ogobara K Doumbo
    • , Noah S Butler
    • , Peter D Crompton
    •  & John T Harty
  • Article |

    Simultaneous activation of Wnt and Shh pathways in murine neural precursor cells results in the formation of embryonal tumors with multilayered rosettes (ETMR) that recapitulate the histological and molecular features of human tumors. This novel mouse model represents a platform for evaluating therapeutic approaches for this rare malignant pediatric brain tumor, and provides novel insights into the cell of origin and molecular mechanisms driving the disease.

    • Julia E Neumann
    • , Annika K Wefers
    • , Sander Lambo
    • , Edoardo Bianchi
    • , Marie Bockstaller
    • , Mario M Dorostkar
    • , Valerie Meister
    • , Pia Schindler
    • , Andrey Korshunov
    • , Katja von Hoff
    • , Johannes Nowak
    • , Monika Warmuth-Metz
    • , Marlon R Schneider
    • , Ingrid Renner-Müller
    • , Daniel J Merk
    • , Mehdi Shakarami
    • , Tanvi Sharma
    • , Lukas Chavez
    • , Rainer Glass
    • , Jennifer A Chan
    • , M Mark Taketo
    • , Philipp Neumann
    • , Marcel Kool
    •  & Ulrich Schüller

News & Comment

Natureevents Directory