Frederic Cantin, Labonté Lab.

Microglia emerge as central players in brain disease

Latest Research

  • Article |

    Amplification of chromosome 1q21.3 distinguishes cells with tumor-initiating capacity that drive tumor recurrence across different breast cancer subtypes. A droplet digital PCR assay in circulating free tumor DNA identifies patients with early-stage cancer at high risk of relapse and predicts response to therapy in the metastatic setting. Pharmacological blockade of targets within this amplicon using a clinically available compound prevents tumor recurrence, suggesting a potential therapeutic approach to improve the clinical management of patients harboring 1q21.3-amplified breast tumors.

    • Jian Yuan Goh
    • , Min Feng
    • , Wenyu Wang
    • , Gokce Oguz
    • , Siti Maryam J M Yatim
    • , Puay Leng Lee
    • , Yi Bao
    • , Tse Hui Lim
    • , Panpan Wang
    • , Wai Leong Tam
    • , Annette R Kodahl
    • , Maria B Lyng
    • , Suman Sarma
    • , Selena Y Lin
    • , Alexander Lezhava
    • , Yoon Sim Yap
    • , Alvin S T Lim
    • , Dave S B Hoon
    • , Henrik J Ditzel
    • , Soo Chin Lee
    • , Ern Yu Tan
    •  & Qiang Yu
  • 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

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