A5015184631- Advanced Proteomics Techniques and Applications
- Mass Spectrometry Techniques and Applications
- Ubiquitin and proteasome pathways
- Cancer Genomics and Diagnostics
- Ferroptosis and cancer prognosis
- RNA modifications and cancer
- Metabolomics and Mass Spectrometry Studies
- Bioinformatics and Genomic Networks
- Protein Degradation and Inhibitors
- Molecular Biology Techniques and Applications
- Gene expression and cancer classification
- Cancer-related Molecular Pathways
- Neurobiology and Insect Physiology Research
- Analytical Chemistry and Chromatography
- Advanced Biosensing Techniques and Applications
- Pancreatic and Hepatic Oncology Research
- Multiple Myeloma Research and Treatments
- Receptor Mechanisms and Signaling
- Data Mining Algorithms and Applications
- Glycosylation and Glycoproteins Research
- Customer churn and segmentation
- AI-based Problem Solving and Planning
- Cancer Research and Treatments
- Monoclonal and Polyclonal Antibodies Research
- Epigenetics and DNA Methylation
Broad Institute
2016-2025
Massachusetts Institute of Technology
2006-2024
James S. McDonnell Foundation
2024
Washington University in St. Louis
2024
Harvard University
2005-2024
Intelligent Health (United Kingdom)
2024
Brigham Young University
2023
Wroclaw Medical University
2023
National Cancer Institute
2019-2023
Cancer Clinic
2023
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...
To elucidate the deregulated functional modules that drive clear cell renal carcinoma (ccRCC), we performed comprehensive genomic, epigenomic, transcriptomic, proteomic, and phosphoproteomic characterization of treatment-naive ccRCC paired normal adjacent tissue samples. Genomic analyses identified a distinct molecular subgroup associated with genomic instability. Integration proteogenomic measurements uniquely protein dysregulation cellular mechanisms impacted by alterations, including...
Adoption of targeted mass spectrometry (MS) approaches such as multiple reaction monitoring (MRM) to study biological and biomedical questions is well underway in the proteomics community. Successful application depends on ability generate reliable assays that uniquely confidently identify target peptides a sample. Unfortunately, there wide range criteria being applied say an assay has been successfully developed. There no consensus what are acceptable little understanding impact variable...
Glioblastoma (GBM) is the most aggressive nervous system cancer. Understanding its molecular pathogenesis crucial to improving diagnosis and treatment. Integrated analysis of genomic, proteomic, post-translational modification metabolomic data on 99 treatment-naive GBMs provides insights GBM biology. We identify key phosphorylation events (e.g., phosphorylated PTPN11 PLCG1) as potential switches mediating oncogenic pathway activation, well targets for EGFR-, TP53-, RB1-altered tumors. Immune...
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...
We undertook a comprehensive proteogenomic characterization of 95 prospectively collected endometrial carcinomas, comprising 83 endometrioid and 12 serous tumors. This analysis revealed possible new consequences perturbations to the p53 Wnt/β-catenin pathways, identified potential role for circRNAs in epithelial-mesenchymal transition, provided information about proteomic markers clinical genomic tumor subgroups, including relationships known druggable pathways. An extensive genome-wide...
Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive cancer with poor patient survival. Toward understanding the underlying molecular alterations that drive PDAC oncogenesis, we conducted comprehensive proteogenomic analysis of 140 pancreatic cancers, 67 normal adjacent tissues, and 9 tissues. Proteomic, phosphoproteomic, glycoproteomic analyses were used to characterize proteins their modifications. In addition, whole-genome sequencing, whole-exome methylation, RNA sequencing...
Protein abundance and phosphorylation convey important information about pathway activity molecular pathophysiology in diseases including cancer, providing biological insight, informing drug diagnostic development, guiding therapeutic intervention. Analyzed tissues are usually collected without tight regulation or documentation of ischemic time. To evaluate the impact ischemia, we human ovarian tumor breast cancer xenograft tissue vascular interruption performed quantitative proteomics...
Pancreatic ductal adenocarcinoma (PDAC) has prominent extracellular matrix (ECM) that compromises treatments yet cannot be nonselectively disrupted without adverse consequences. ECM of PDAC, despite the recognition its importance, not been comprehensively studied in patients. In this study, we used quantitative mass spectrometry (MS)-based proteomics to characterize proteins normal pancreas and pancreatic intraepithelial neoplasia (PanIN)- PDAC-bearing from both human patients mouse genetic...
Most small-molecule probes and drugs alter cell circuitry by interacting with 1 or more proteins. A complete understanding of the proteins their associated protein complexes, whether compounds are discovered cell-based phenotypic target-based screens, is extremely rare. Such a capability expected to be highly illuminating—providing strong clues mechanisms used small-molecules achieve recognized actions suggesting potential unrecognized actions. We describe powerful method combining...
Detection of endogenous ubiquitination sites by mass spectrometry has dramatically improved with the commercialization anti-di-glycine remnant (K-ε-GG) antibodies. Here, we describe a number improvements to K-ε-GG enrichment workflow, including optimized antibody and peptide input requirements, cross-linking, off-line fractionation prior enrichment. This refined practical workflow enables routine identification quantification ∼20,000 distinct in single SILAC experiment using moderate amounts...
Verification of candidate biomarkers requires specific assays to selectively detect and quantify target proteins in accessible biofluids. The primary objective verification is screen potential ensure that only the highest quality candidates from discovery phase are taken forward into preclinical validation. Because antibody reagents for a clinical grade immunoassay often exist small number candidates, alternative methodologies required credential new unproven statistically viable serum or...
We present a proteogenomic study of 108 human papilloma virus (HPV)-negative head and neck squamous cell carcinomas (HNSCCs). Proteomic analysis systematically catalogs HNSCC-associated proteins phosphosites, prioritizes copy number drivers, highlights an oncogenic role for RNA processing genes. investigation mutual exclusivity between FAT1 truncating mutations 11q13.3 amplifications reveals dysregulated actin dynamics as common functional consequence. Phosphoproteomics characterizes two...