- Advanced Proteomics Techniques and Applications
- Bioinformatics and Genomic Networks
- Mass Spectrometry Techniques and Applications
- Advanced Biosensing Techniques and Applications
- Metabolomics and Mass Spectrometry Studies
- Genomics and Rare Diseases
- Machine Learning in Bioinformatics
- Gene expression and cancer classification
- Developmental Biology and Gene Regulation
- Connective tissue disorders research
- Cytomegalovirus and herpesvirus research
- Evolution and Genetic Dynamics
- Neurobiology and Insect Physiology Research
- Hippo pathway signaling and YAP/TAZ
- Cardiac Valve Diseases and Treatments
- Computational Drug Discovery Methods
- Immune Cell Function and Interaction
- Chemical Synthesis and Analysis
- Hedgehog Signaling Pathway Studies
- Glycosylation and Glycoproteins Research
- Genomics and Phylogenetic Studies
- Protease and Inhibitor Mechanisms
- Peptidase Inhibition and Analysis
- Click Chemistry and Applications
- Fungal and yeast genetics research
Harvard University
2010-2021
Brigham and Women's Hospital
2010-2018
Tufts University
2013
Vanderbilt University Medical Center
2010
Multiplexed quantitation via isobaric chemical tags (e.g., tandem mass (TMT) and for relative absolute (iTRAQ)) has the potential to revolutionize quantitative proteomics. However, until recently utility of these was questionable due reporter ion ratio distortion resulting from fragmentation coisolated interfering species. These signals can be negated through additional gas-phase manipulations MS/MS/MS (MS3) proton-transfer reactions (PTR)). methods, however, have a significant sensitivity...
A systematic quantitative analysis of temporal changes in host and viral proteins throughout the course a productive infection could provide dynamic insights into virus-host interaction. We developed proteomic technique called "quantitative viromics" (QTV), which employs multiplexed tandem-mass-tag-based mass spectrometry. Human cytomegalovirus (HCMV) is not only an important pathogen but paradigm immune evasion. QTV detailed how HCMV orchestrates expression >8,000 cellular proteins,...
Quantitative proteomics employing isobaric reagents has been established as a powerful tool for biological discovery. Current workflows often utilize dedicated quantitative spectrum to improve accuracy and precision. A consequence of this approach is dramatic reduction in the spectral acquisition rate, which necessitates use additional instrument time achieve comprehensive proteomic depth. This work assesses performance benefits online real-time identification multiplexed workflows....
SUMMARY Thousands of interactions assemble proteins into modules that impart spatial and functional organization to the cellular proteome. Through affinity-purification mass spectrometry, we have created two proteome-scale, cell-line-specific interaction networks. The first, BioPlex 3.0, results from affinity purification 10,128 human – half proteome in 293T cells includes 118,162 among 14,586 proteins; second 5,522 immunoprecipitations HCT116 cells. These networks model interactome at...
Governance of protein phosphorylation by kinases and phosphatases constitutes an essential regulatory network in eukaryotic cells. Network dysregulation leads to severe consequences is often a key factor disease pathogenesis. Previous studies revealed multiple roles for pathway structures cellular functions from different perspectives. We seek understand the homeostasis point view. Using streamlined tandem mass tag (SL-TMT) strategy, we systematically measure proteomic phosphoproteomic...
A precise mixture of extracellular matrix (ECM) secreted by valvular cells forms a scaffold that lends the heart valve exact mechanical and tensile strength needed for accurate hemodynamic performance. ECM proteins are key component endothelial cell (VEC)-valvular interstitial (VIC) communication essential maintenance structure. This study reports healthy adult pulmonary aortic proteomes characterized LC-MS/MS, resulting in 2710 expressed 1513 genes, including over 300 abundant proteins....
Abstract We recently reported the quantitative proteomics of 375 samples as part Cancer Cell Line Encyclopedia (Nusinow et al., 2020). Mass spectrometry-based data is broadly unfamiliar to most biologists in our experience, resulting questions from analysts about how use data. From community there was interest we normalized data, scope this project so much larger than what has been commonly available. This paper serves a guide set answer these and acts supplement main manuscript. The first...
Central to embryonic development is the generation of molecular asymmetries across fields undifferentiated cells. The Drosophila wing imaginal disc provides a powerful system with which understand how such are generated and they contribute formation complex structure. Early in development, primordium subdivided into thin layer peripodial epithelium (PE) an apposing thickened pseudostratified columnar (CE), known as proper (DP). DP gives rise blade, hinge dorsal mesothorax, whereas PE makes...
Proteomics presents the opportunity to provide novel insights about global biochemical state of a tissue. However, significant problem with current methods is that shotgun proteomics has limited success at detecting many low abundance proteins, such as transcription factors from complex mixtures cells and tissues. The ability assay for these proteins in context entire proteome would be useful areas experimental biology.We used network-based inference an approach named SNIPE (Software Network...
The dispensability of individual genes for viability has interested generations geneticists. For some it is essential to maintain two functional chromosomal copies, while other may tolerate the loss one or both copies. Exome sequence data from 60,706 individuals provide sufficient observations rare protein truncating variants (PTVs) make genome-wide estimates selection against heterozygous gene function. cumulative frequency deleterious PTVs primarily determined by balance between incoming...