Amanda G. Paulovich
A5022925020- Advanced Proteomics Techniques and Applications
- Mass Spectrometry Techniques and Applications
- Metabolomics and Mass Spectrometry Studies
- Cancer Genomics and Diagnostics
- DNA Repair Mechanisms
- RNA modifications and cancer
- Bioinformatics and Genomic Networks
- Ferroptosis and cancer prognosis
- Monoclonal and Polyclonal Antibodies Research
- Molecular Biology Techniques and Applications
- Ubiquitin and proteasome pathways
- Advanced biosensing and bioanalysis techniques
- CAR-T cell therapy research
- Advanced Biosensing Techniques and Applications
- Gene expression and cancer classification
- Cancer-related Molecular Pathways
- Carcinogens and Genotoxicity Assessment
- Viral Infectious Diseases and Gene Expression in Insects
- Machine Learning in Bioinformatics
- Glycosylation and Glycoproteins Research
- Cancer, Hypoxia, and Metabolism
- Immunotherapy and Immune Responses
- Cancer, Lipids, and Metabolism
- Genetic factors in colorectal cancer
- Lung Cancer Treatments and Mutations
Fred Hutch Cancer Center
2015-2024
University of Washington
1993-2024
Target (United States)
2023
Brotman Baty Institute
2023
Fusion Academy
2020
Fusion (United States)
2020
Clinical Research Consortium
2020
Seattle University
2020
Cape Town HVTN Immunology Laboratory / Hutchinson Centre Research Institute of South Africa
1998-2018
Cancer Research Center
2006-2018
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...
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...
The complexity of proteomic instrumentation for LC-MS/MS introduces many possible sources variability. Data-dependent sampling peptides constitutes a stochastic element at the heart discovery proteomics. Although this variation impacts identification peptides, identifications are far from completely random. In study, we analyzed interlaboratory data sets NCI Clinical Proteomic Technology Assessment Cancer to examine repeatability and reproducibility in peptide protein identifications....
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...
How potently CAR T cells with CD28 or 4-1BB costimulatory domains stimulate intracellular signaling correlates treatment efficacy.
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...
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...
There is an urgent need for quantitative assays in verifying and validating the large numbers of protein biomarker candidates produced modern “-omics” experiments. Stable isotope standards with capture by anti-peptide antibodies (SISCAPA) has shown tremendous potential to meet this combining peptide immunoaffinity enrichment mass spectrometry. In study, we describe three significant advances SISCAPA technique. First, develop a method automated magnetic bead-based platform capable high...
The National Cancer Institute (NCI) Clinical Proteomic Tumor Analysis Consortium is applying the latest generation of proteomic technologies to genomically annotated tumors from Genome Atlas (TCGA) program, a joint initiative NCI and Human Research Institute. By providing fully integrated accounting DNA, RNA, protein abnormalities in individual tumors, these datasets will illuminate complex relationship between genomic cancer phenotypes, thus producing biologic insights as well wave novel...
Lung squamous cell carcinoma (LSCC) remains a leading cause of cancer death with few therapeutic options. We characterized the proteogenomic landscape LSCC, providing deeper exposition LSCC biology potential implications. identify NSD3 as an alternative driver in FGFR1-amplified tumors and low-p63 overexpressing target survivin. SOX2 is considered undruggable, but our analyses provide rationale for exploring chromatin modifiers such LSD1 EZH2 to SOX2-overexpressing tumors. Our data support...
We report a comprehensive proteogenomics analysis, including whole-genome sequencing, RNA and proteomics phosphoproteomics profiling, of 218 tumors across 7 histological types childhood brain cancer: low-grade glioma (n = 93), ependymoma (32), high-grade (25), medulloblastoma (22), ganglioglioma (18), craniopharyngioma (16), atypical teratoid rhabdoid tumor (12). Proteomics data identify common biological themes that span boundaries, suggesting treatments used for one type may be applied...
Panorama is a web application for storing, sharing, analyzing, and reusing targeted assays created refined with Skyline,1 an increasingly popular Windows client software tool proteomics experiments. allows laboratories to store organize curated results contained in Skyline documents fine-grained permissions, which facilitates distributed collaboration secure sharing of published unpublished data via web-browser interface. It fully integrated the workflow supports publishing document directly...
For many years, basic and clinical researchers have taken advantage of the analytical sensitivity specificity afforded by mass spectrometry in measurement proteins. Clinical laboratories are now beginning to deploy these work flows as well. assays that use proteolysis generate peptides for protein quantification characterization, synthetic stable isotope-labeled internal standard central importance. No general recommendations currently available surrounding spectrometric assays.The Proteomic...
There is an increasing need in biology and clinical medicine to robustly reliably measure tens hundreds of peptides proteins biological samples with high sensitivity, specificity, reproducibility, repeatability. Previously, we demonstrated that LC-MRM-MS isotope dilution has suitable performance for quantitative measurements small numbers relatively abundant human plasma the resulting assays can be transferred across laboratories while maintaining reproducibility precision. Here,...
Diffuse intrinsic pontine glioma (DIPG) remains a fatal brainstem tumor demanding innovative therapies. As B7-H3 (CD276) is expressed on central nervous system (CNS) tumors, we designed B7-H3-specific chimeric antigen receptor (CAR) T cells, confirmed their preclinical efficacy, and opened BrainChild-03 (NCT04185038), first-in-human phase I trial administering repeated locoregional CAR cells to children with recurrent/refractory CNS tumors DIPG. Here, report the results of first three...