A5020040021- Advanced Proteomics Techniques and Applications
- Mass Spectrometry Techniques and Applications
- Protein Tyrosine Phosphatases
- Metabolomics and Mass Spectrometry Studies
- ATP Synthase and ATPases Research
- Ferroptosis and cancer prognosis
- Bioinformatics and Genomic Networks
- CRISPR and Genetic Engineering
- RNA Research and Splicing
- Fungal and yeast genetics research
- RNA and protein synthesis mechanisms
- Bacteriophages and microbial interactions
- RNA modifications and cancer
- Prion Diseases and Protein Misfolding
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Bioactive Compounds and Antitumor Agents
- Protein Degradation and Inhibitors
- Protein Structure and Dynamics
- Galectins and Cancer Biology
- Ubiquitin and proteasome pathways
- Biotin and Related Studies
- Genomics and Chromatin Dynamics
- Lung Cancer Treatments and Mutations
- Enzyme Structure and Function
- DNA Repair Mechanisms
Columbia University
2020-2025
Broad Institute
2018-2020
Massachusetts Institute of Technology
2020
To explore the biology of lung adenocarcinoma (LUAD) and identify new therapeutic opportunities, we performed comprehensive proteogenomic characterization 110 tumors 101 matched normal adjacent tissues (NATs) incorporating genomics, epigenomics, deep-scale proteomics, phosphoproteomics, acetylproteomics. Multi-omics clustering revealed four subgroups defined by key driver mutations, country, gender. Proteomic phosphoproteomic data illuminated downstream copy number aberrations, somatic...
The integration of mass spectrometry-based proteomics with next-generation DNA and RNA sequencing profiles tumors more comprehensively. Here this "proteogenomics" approach was applied to 122 treatment-naive primary breast cancers accrued preserve post-translational modifications, including protein phosphorylation acetylation. Proteogenomics challenged standard cancer diagnoses, provided detailed analysis the ERBB2 amplicon, defined tumor subsets that could benefit from immune checkpoint...
Defense-associated reverse transcriptase (DRT) systems perform DNA synthesis to protect bacteria against viral infection, but the identities and functions of their products remain largely unknown. We show that DRT2 encode an unprecedented immune pathway involves de novo gene through rolling circle transcription a noncoding RNA (ncRNA). Programmed template jumping on ncRNA generates concatemeric cDNA, which becomes double-stranded upon infection. This product constitutes protein-coding,...
Alternative polyadenylation (APA) creates distinct transcripts from the same gene by cleaving pre-mRNA at poly(A) sites that can lie within 3′ untranslated region (3′UTR), introns, or exons. Most studies focus on APA 3′UTR; however, here, we show CPSF6 insufficiency alters protein levels and causes a developmental syndrome deregulating throughout transcript. In neonatal humans zebrafish larvae, shifts site usage between 3′UTR internal in pathway-specific manner. Genes associated with...
A protein's molecular interactions and post-translational modifications (PTMs), such as phosphorylation, can be co-dependent reciprocally co-regulate each other. Although this interplay is central for many biological processes, a systematic method to simultaneously study assembly states PTMs from the same sample critically missing. Here, we introduce SEC-MX (Size Exclusion Chromatography fractions MultipleXed), global quantitative combining Size PTM-enrichment simultaneous characterization...
Abstract Missense mutations in PTPN11 , the gene encoding protein tyrosine phosphatase SHP2, are common several developmental disorders and cancers. While many SHP2 disrupt auto-inhibition cause hyperactivity, do not enhance catalytic activity. Both activating non-activating could potentially drive pathogenic signaling by altering protein-protein interactions or subcellular localization. We employed proximity-labeling proteomics to map interaction networks of wild-type ten...
Electrospray ionization is a powerful and prevalent technique used to ionize analytes in mass spectrometry. The distribution of charges that an analyte receives (charge state distribution, CSD) important consideration for interpreting spectra. However, due incomplete understanding the mechanism, properties influence CSDs are not fully understood. Here, we employ machine learning-based approach analyze hundreds thousands peptides. Interestingly, half peptides exhibit differ from what one...
Bacteria defend themselves from viral infection using diverse immune systems, many of which sense and target foreign nucleic acids. Defense-associated reverse transcriptase (DRT) systems provide an intriguing counterpoint to this strategy by instead leveraging DNA synthesis, but the identities functions their products remain largely unknown. Here we show that DRT2 execute unprecedented immunity mechanism involves de novo gene synthesis via rolling-circle transcription a non-coding RNA...
Amyloid-like protein assemblies have been associated with toxic phenotypes because of their repetitive and stable structure. However, evidence that cells exploit these structures to control function activity some proteins in response stimuli has questioned this paradigm. How amyloid-like assembly can confer emergent functions how couple environmental conditions remains unclear. Here, we study Rim4, an RNA-binding forms translation-repressing during yeast meiosis. We demonstrate its assembled...
Protein tyrosine phosphatases (PTPs) are an important class of enzymes that modulate essential cellular processes through protein dephosphorylation and dysregulated in various disease states. There is demand for new compounds target the active sites these enzymes, use as chemical tools to dissect their biological roles or leads development therapeutics. In this study, we explore array electrophiles fragment scaffolds investigate required parameters covalent inhibition phosphatases. Our...
Protein molecular interactions and post-translational modifications (PTMs), such as phosphorylation, can be co-dependent reciprocally co-regulate each other. Although this interplay is central for many biological processes, a systematic method to simultaneously study assembly-states PTMs from the same sample critically missing. Here, we introduce SEC-MX (Size Exclusion Chromatography fractions MultipleXed), global quantitative combining Size PTM-enrichment simultaneous characterization of...
Protein tyrosine phosphatases (PTPs) are an important class of enzymes that modulate essential cellular processes through protein dephosphorylation and dysregulated in various disease states. There is demand for new compounds target the active sites these enzymes, use as chemical tools to dissect their biological roles or leads development therapeutics. In this study, we explore array electrophiles fragment scaffolds investigate required parameters covalent inhibition phosphatases. Our...
Abstract Electrospray ionization is a powerful and prevalent technique used to ionize analytes in mass spectrometry. The distribution of charges that an analyte receives (charge state distribution, CSD) important consideration for interpreting spectra. However, due incomplete understanding the mechanism, properties influence CSDs are not fully understood. Here, we employ machine learning-based high-throughput approach analyze hundreds thousands peptides. Interestingly, half peptides exhibit...
Abstract A persistent central deficiency in our knowledge of cancer concerns how genomic changes drive the proteome and phosphoproteome to execute phenotypic characteristics. Furthermore increasing evidence implicating epigenetic post-translational biology reinforce notion that molecular profiles based on nucleic acids are incomplete critically complemented by analyses proteins their modifications. We present first integrated proteogenomic study a prospectively collected breast cohort,...
Protein tyrosine phosphatases (PTPs) are an important class of enzymes that modulate essential cellular processes through protein dephosphorylation and dysregulated in various disease states. There is demand for new compounds target the active sites these enzymes, use as chemical tools to dissect their biological roles or leads development therapeutics. In this study, we explore array electrophiles fragment scaffolds investigate required parameters covalent inhibition phosphatases. Our...