Journal: Nature Medicine

Abbreviation

Nat Med

Publisher

Nature

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ISSN

1078-8956
1546-170X

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Publications1 - 10 of 60
  • Can experiments in nonhuman primates expedite the translation of treatments for spinal cord injury in humans?
    Item type: Journal Article
    Courtine, Grégoire; Bunge, Mary B.; Fawcett, James W.; et al. (2007)
    Nature Medicine
  • A public antibody lineage that potently inhibits malaria infection through dual binding to the circumsporozoite protein
    Item type: Journal Article
    Tan, Joshua; Sack, Brandon K.; Oyen, David; et al. (2018)
    Nature Medicine
  • Rapid mass spectrometric conversion of tissue biopsy samples into permanent quantitative digital proteome maps
    Item type: Journal Article
    Guo, Tiannan; Kouvonen, Petri; Koh, Ching Chiek; et al. (2015)
    Nature Medicine
  • Actionable druggable genome-wide Mendelian randomization identifies repurposing opportunities for COVID-19
    Item type: Journal Article
    VA Million Veteran Program COVID-19 Science Initiative; Gaziano, Liam; Giambartolomei, Claudia; et al. (2021)
    Nature Medicine
    Drug repurposing provides a rapid approach to meet the urgent need for therapeutics to address COVID-19. To identify therapeutic targets relevant to COVID-19, we conducted Mendelian randomization analyses, deriving genetic instruments based on transcriptomic and proteomic data for 1,263 actionable proteins that are targeted by approved drugs or in clinical phase of drug development. Using summary statistics from the Host Genetics Initiative and the Million Veteran Program, we studied 7,554 patients hospitalized with COVID-19 and >1 million controls. We found significant Mendelian randomization results for three proteins (ACE2, P = 1.6 × 10−6; IFNAR2, P = 9.8 × 10−11 and IL-10RB, P = 2.3 × 10−14) using cis-expression quantitative trait loci genetic instruments that also had strong evidence for colocalization with COVID-19 hospitalization. To disentangle the shared expression quantitative trait loci signal for IL10RB and IFNAR2, we conducted phenome-wide association scans and pathway enrichment analysis, which suggested that IFNAR2 is more likely to play a role in COVID-19 hospitalization. Our findings prioritize trials of drugs targeting IFNAR2 and ACE2 for early management of COVID-19.
  • An AMP-activated protein kinase-stabilizing peptide ameliorates adipose tissue wasting in cancer cachexia in mice
    Item type: Journal Article
    Rohm, Maria; Schäfer, Michaela; Laurent, Victor; et al. (2016)
    Nature Medicine
  • An organotypic atlas of human vascular cells
    Item type: Journal Article
    Barnett, Sam N.; Cujba, Ana-Maria; Yang, Lu; et al. (2024)
    Nature Medicine
    The human vascular system, comprising endothelial cells (ECs) and mural cells, covers a vast surface area in the body, providing a critical interface between blood and tissue environments. Functional differences exist across specific vascular beds, but their molecular determinants across tissues remain largely unknown. In this study, we integrated single-cell transcriptomics data from 19 human organs and tissues and defined 42 vascular cell states from approximately 67,000 cells (62 donors), including angiotypic transitional signatures along the arterial endothelial axis from large to small caliber vessels. We also characterized organotypic populations, including splenic littoral and blood-brain barrier ECs, thus clarifying the molecular profiles of these important cell states. Interrogating endothelial-mural cell molecular crosstalk revealed angiotypic and organotypic communication pathways related to Notch, Wnt, retinoic acid, prostaglandin and cell adhesion signaling. Transcription factor network analysis revealed differential regulation of downstream target genes in tissue-specific modules, such as those of FOXF1 across multiple lung vascular subpopulations. Additionally, we make mechanistic inferences of vascular drug targets within different vascular beds. This open-access resource enhances our understanding of angiodiversity and organotypic molecular signatures in human vascular cells, and has therapeutic implications for vascular diseases across tissues.
  • Toll-like receptor engagement converts T-cell autoreactivity into overt autoimmune disease
    Item type: Journal Article
    Lang, K.S.; Recher, M.; Junt, T.; et al. (2005)
    Nature Medicine
  • High-throughput identification of repurposable neuroactive drugs with potent anti-glioblastoma activity
    Item type: Journal Article
    Lee, Sohyon; Weiss, Tobias; Bühler, Marcel Christoph; et al. (2024)
    Nature Medicine
    Glioblastoma, the most aggressive primary brain cancer, has a dismal prognosis, yet systemic treatment is limited to DNA-alkylating chemotherapies. New therapeutic strategies may emerge from exploring neurodevelopmental and neurophysiological vulnerabilities of glioblastoma. To this end, we systematically screened repurposable neuroactive drugs in glioblastoma patient surgery material using a clinically concordant and single-cell resolved platform. Profiling more than 2,500 ex vivo drug responses across 27 patients and 132 drugs identified class-diverse neuroactive drugs with potent anti-glioblastoma efficacy that were validated across model systems. Interpretable molecular machine learning of drug-target networks revealed neuroactive convergence on AP-1/BTG-driven glioblastoma suppression, enabling expanded in silico screening of more than 1 million compounds with high patient validation accuracy. Deep multimodal profiling confirmed Ca2+-driven AP-1/BTG-pathway induction as a neuro-oncological glioblastoma vulnerability, epitomized by the anti-depressant vortioxetine synergizing with current standard-of-care chemotherapies in vivo. These findings establish an actionable framework for glioblastoma treatment rooted in its neural etiology.
  • Secrets of microbiota drug metabolism
    Item type: Other Journal Item
    Macpherson, Andrew J.; Sauer, Uwe (2023)
    Nature Medicine
    High-resolution meta-omics have enabled the discovery of the microbial enzymes that inactivate an ulcerative colitis drug and predict subsequent treatment failure, an approach that could enable more personalized treatment of inflammatory bowel disease.
  • Opposing effects of cancer-type-specific SPOP mutants on BET protein degradation and sensitivity to BET inhibitors
    Item type: Journal Article
    Janouskova, Hana; El Tekle, Geniver; Bellini, Elisa; et al. (2017)
    Nature Medicine
Publications1 - 10 of 60