A5068971521- Mitochondrial Function and Pathology
- Metabolism and Genetic Disorders
- RNA modifications and cancer
- ATP Synthase and ATPases Research
- Adipose Tissue and Metabolism
- Ferroptosis and cancer prognosis
- Metabolomics and Mass Spectrometry Studies
- Cancer, Hypoxia, and Metabolism
- RNA and protein synthesis mechanisms
- Cancer, Lipids, and Metabolism
- Cancer-related molecular mechanisms research
- Genomics and Rare Diseases
- Bioinformatics and Genomic Networks
- RNA Research and Splicing
- Photosynthetic Processes and Mechanisms
- Diet and metabolism studies
- Advanced Proteomics Techniques and Applications
- Neuroscience and Neuropharmacology Research
- Folate and B Vitamins Research
- Ovarian cancer diagnosis and treatment
- Genomics and Phylogenetic Studies
- Biotin and Related Studies
- Gene expression and cancer classification
- RNA regulation and disease
- Genetic Neurodegenerative Diseases
Broad Institute
2016-2025
Center for Systems Biology
2016-2025
Harvard University
2016-2025
Massachusetts General Hospital
2016-2025
Howard Hughes Medical Institute
2016-2025
Massachusetts Institute of Technology
2006-2024
Epizyme (United States)
2024
Daiichi Sankyo (Germany)
2024
Janssen (France)
2024
Daiichi-Sankyo (South Korea)
2024
Although genomewide RNA expression analysis has become a routine tool in biomedical research, extracting biological insight from such information remains major challenge. Here, we describe powerful analytical method called Gene Set Enrichment Analysis (GSEA) for interpreting gene data. The derives its power by focusing on sets, that is, groups of genes share common function, chromosomal location, or regulation. We demonstrate how GSEA yields insights into several cancer-related data...
More Glycine, Please To better characterize metabolic properties of cancer cells, Jain et al. (p. 1040 ; see the Perspective by Tomita and Kami ) measured systematically concentrations hundreds metabolites in cell culture medium which 60 different lines were growing. The fastest growing cells tended to consume glycine, whereas more slowly excreted some glycine. rapidly appeared need glycine for synthesis purine nucleotides required continued DNA. Interfering with metabolism slowed growth...
Mitochondria are complex organelles that house essential pathways involved in energy metabolism, ion homeostasis, signalling and apoptosis. To understand mitochondrial health disease, it is crucial to have an accurate inventory of the organelle's protein components. In 2008, we made substantial progress toward this goal by performing in-depth mass spectrometry mitochondria from 14 organs, epitope tagging/microscopy Bayesian integration assemble MitoCarta...
Abstract The mammalian mitochondrial proteome is under dual genomic control, with 99% of proteins encoded by the nuclear genome and 13 originating from DNA (mtDNA). We previously developed MitoCarta, a catalogue over 1000 genes encoding proteome. This was compiled using Bayesian integration multiple sequence features experimental datasets, notably protein mass spectrometry mitochondria isolated fourteen murine tissues. Here, we introduce MitoCarta3.0. Beginning MitoCarta2.0 inventory,...
TNFR1/Fas engagement results in the cleavage of cytosolic BID to truncated tBID, which translocates mitochondria. Immunodepletion and gene disruption indicate is required for cytochrome c release. Surprisingly, three-dimensional structure this BH3 domain-only molecule revealed two hydrophobic alpha-helices suggesting tBID itself might be a pore-forming protein. Instead, we demonstrate that functions as membrane-targeted death ligand an intact domain release, but not targeting. Bak-deficient...
Microscopy and mass spectrometry (MS) are complementary techniques: The former provides spatiotemporal information in living cells, but only for a handful of recombinant proteins at time, whereas the latter can detect thousands endogenous simultaneously, lysed samples. Here, we introduce technology that combines these strengths by offering spatially temporally resolved proteomic maps within cells. Our method relies on genetically targetable peroxidase enzyme biotinylates nearby proteins,...
Upstream ORFs (uORFs) are mRNA elements defined by a start codon in the 5' UTR that is out-of-frame with main coding sequence. Although uORFs present approximately half of human and mouse transcripts, no study has investigated their global impact on protein expression. Here, we report correlate significantly reduced expression downstream ORF, based analysis 11,649 matched measurements from 4 published mammalian studies. Using reporter constructs to test 25 selected uORFs, estimate typically...
Uncoupling protein 3 (UCP3) is a member of the mitochondrial anion carrier superfamily. Based upon its high homology with UCP1 and restricted tissue distribution to skeletal muscle brown adipose tissue, UCP3 has been suggested play important roles in regulating energy expenditure, body weight, thermoregulation. Other postulated for include regulation fatty acid metabolism, adaptive responses acute exercise starvation, prevention reactive oxygen species (ROS) formation. To address these...
Recent studies have shown that genes involved in oxidative phosphorylation (OXPHOS) exhibit reduced expression skeletal muscle of diabetic and prediabetic humans. Moreover, these changes may be mediated by the transcriptional coactivator peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC-1alpha). By combining PGC-1alpha-induced genome-wide profiles with a computational strategy to detect cis-regulatory motifs, we identified estrogen-related alpha (Erralpha) GA...
The mitochondrial uniporter is a highly selective calcium channel in the organelle's inner membrane. Its molecular components include EF-hand-containing calcium-binding proteins uptake 1 (MICU1) and MICU2 pore-forming subunit (MCU). We sought to achieve full characterization of holocomplex (uniplex). Quantitative mass spectrometry affinity-purified uniplex recovered MICU1 MICU2, MCU its paralog MCUb, essential regulator (EMRE), previously uncharacterized protein. EMRE 10-kilodalton,...