A5000977764- Advanced Proteomics Techniques and Applications
- Mass Spectrometry Techniques and Applications
- Genetic and phenotypic traits in livestock
- Metabolomics and Mass Spectrometry Studies
- Animal Behavior and Welfare Studies
- Pancreatitis Pathology and Treatment
- Animal Nutrition and Physiology
- Pancreatic and Hepatic Oncology Research
- RNA and protein synthesis mechanisms
- Pancreatic function and diabetes
- COVID-19 Clinical Research Studies
- Enzyme Structure and Function
- Genetic Mapping and Diversity in Plants and Animals
- Immune responses and vaccinations
- Genomics and Phylogenetic Studies
- Neonatal Respiratory Health Research
- Glycosylation and Glycoproteins Research
- SARS-CoV-2 and COVID-19 Research
- Alzheimer's disease research and treatments
- Long-Term Effects of COVID-19
- Cancer-related gene regulation
- Renal and related cancers
- Advanced Biosensing Techniques and Applications
- Immune cells in cancer
- Diabetes and associated disorders
Boston Children's Hospital
2016-2025
Harvard University
2016-2025
Boston Children's Museum
2014-2025
Boston University
2020-2024
Brigham and Women's Hospital
2001-2024
The Coordinating Center
2024
Texas Children's Hospital
2023
Baylor College of Medicine
2023
Harvard University Press
2003-2021
MRC Unit the Gambia
2019-2021
Quantitative proteomics has traditionally been performed by two-dimensional gel electrophoresis, but recently, mass spectrometric methods based on stable isotope quantitation have shown great promise for the simultaneous and automated identification of complex protein mixtures. Here we describe a method, termed SILAC, labeling amino acids in cell culture, vivo incorporation specific into all mammalian proteins. Mammalian lines are grown media lacking standard essential acid supplemented with...
Human Protein Reference Database (HPRD) is an object database that integrates a wealth of information relevant to the function human proteins in health and disease. Data pertaining thousands protein-protein interactions, posttranslational modifications, enzyme/substrate relationships, disease associations, tissue expression, subcellular localization were extracted from literature for nonredundant set 2750 proteins. Almost all was obtained manually by biologists who read interpreted >300,000...
To elucidate the role of Tau isoforms and post-translational modification (PTM) stoichiometry in Alzheimer's disease (AD), we generated a high-resolution quantitative proteomics map 95 PTMs on multiple isolated from postmortem human tissue 49 AD 42 control subjects. Although PTM maps reveal heterogeneity across subjects, subset display high occupancy frequency for AD, suggesting importance disease. Unsupervised analyses indicate that occur an ordered manner, leading to aggregation. The...
Objective We previously identified a circulating autoantibody against 43 kDa muscle autoantigen in sporadic inclusion body myositis (IBM) and demonstrated the feasibility of an IBM diagnostic blood test. Here, we sought to identify molecular target this autoantibody, understand relationship between autoimmunity degeneration, develop test with high accuracy. Methods samples were screened using mass spectrometry synthetic human peptidome. Plasma serum (N=200 patients) underwent immunoblotting...
Protein S-acylation (palmitoylation), a reversible post-translational modification, is critically involved in regulating protein subcellular localization, activity, stability, and multimeric complex assembly. However, proteome scale characterization of has lagged far behind that phosphorylation, global analysis the localization S-acylated proteins within different membrane domains not been reported. Here we describe novel proteomics approach, designated palmitoyl identification site...
The Mycobacterium tuberculosis genome encodes 11 serine/threonine protein kinases (STPKs) that are structurally related to eukaryotic kinases. To gain insight into the role of Ser/Thr phosphorylation in this major global pathogen, we used a phosphoproteomic approach carry out an extensive analysis M. . We identified more than 500 events 301 proteins involved broad range functions. Bioinformatic quantitative vitro kinase assays on peptides containing subset these sites revealed dominant motif...
T cell acute lymphoblastic leukemia (T-ALL) is an aggressive cancer that frequently associated with activating mutations in NOTCH1 and dysregulation of MYC. Here, we performed 2 complementary screens to identify FDA-approved drugs drug-like small molecules activity against T-ALL. We developed a zebrafish system screen for toxic toward MYC-overexpressing thymocytes used human T-ALL line synergize Notch inhibitors. identified the antipsychotic drug perphenazine both due its ability induce...
Systems biology can unravel complex but has not been extensively applied to human newborns, a group highly vulnerable wide range of diseases. We optimized methods extract transcriptomic, proteomic, metabolomic, cytokine/chemokine, and single cell immune phenotyping data from <1 ml blood, volume readily obtained newborns. Indexing baseline applying innovative integrative computational reveals dramatic changes along remarkably stable developmental trajectory over the first week life. This is...
We introduce a cost-effective, robust high-throughput–compatible plasma depletion method enabling in-depth profiling of that detects >1300 proteins per run with throughput 60 samples day. The has been fully validated by processing >3000 no apparent batch effect at cost for the step ~$2.5 sample.
Abstract Post-acute sequelae of SARS-CoV-2 (PASC) is a significant public health concern. We describe Patient Reported Outcomes (PROs) on 590 participants prospectively assessed from hospital admission for COVID-19 through one year after discharge. Modeling identified 4 PRO clusters based reported deficits (minimal, physical, mental/cognitive, and multidomain), supporting heterogenous clinical presentations in PASC, with sub-phenotypes associated female sex distinctive comorbidities. During...
Phosphorylation is a common form of protein modification. To understand its biological role, the site phosphorylation has to be determined. Generally, only limited amounts phosphorylated proteins are present in cell, thus demanding highly sensitive procedures for determination. Here, novel method introduced which enables localization tyrosine gel-separated femtomol range. The utilizes immonium ion phosphotyrosine at m/z 216.043 positive mode precursor scanning combined with recently...
The Wave proteins are major activators of the Arp2/3 complex. ubiquitous Wave-2 is required for actin polymerization at leading edge migrating cells. Here we purify from HeLa Five proteins, Sra, Nap, Wave-2, Abi, and Hspc, copurified, indicating that they form a tight These only present in complexed form, with exception which displays free pool. We reconstitute complex by cotranslating vitro five subunits use this system together specific immunoprecipitations to study molecular architecture...
Protein expression profiles in yeast cells, response to salinity stress, were determined using the cleavable isotope-coded affinity tag (cICAT) labeling strategy. The analysis included separation of mixed protein samples by SDS-PAGE, followed excision entire gel lane, and division lane into 14 regions. Regions subjected in-gel digestion, biotin chromatography, nano-scale microcapillary liquid chromatography coupled tandem mass spectrometry. novel (13)C-labeled ICAT reagents have identical...
Qualitative and quantitative information are crucial to a detailed understanding of the function protein phosphorylation. MS is now becoming approach analyze All methods that have been described either require elaborate/expensive use stable isotopes compare limited number samples or do not provide phosphorylation stoichiometries. Here, we present isotope-free strategies allow relative absolute quantitation By using developed methods, can normalize robustly account for run-to-run variations...
Protein identification by tandem mass spectrometry is based on the reliable processing of acquired data. Unfortunately, generation a large number poor quality spectra commonly observed in LC-MS/MS, and these mostly noninformative with its associated costs should be avoided. We present continuous score that can computed very quickly considered an approximation MASCOT case correct identification. This used to reject low prior database identification, or draw attention those exhibit...
Phosphorylation is one of the most common forms protein modification. The frequent targets for phosphorylation in eukaryotes are serine and threonine residues, although tyrosine residues also undergo phosphorylation. Many currently applied methods detection localization sites mass spectrometry-based biased against analysis tyrosine-phosphorylated because stability low reactivity phosphotyrosines. To overcome this lack sensitive phosphotyrosine-containing peptides, we have recently developed...
Increased carbamylation of serum albumin is associated with increased mortality in patients kidney failure.
A sheet of choroid plexus epithelial cells extends into each cerebral ventricle and secretes signaling factors the CSF. To evaluate whether differences in CSF proteome across ventricles arise, part, from regional gene expression, we defined transcriptome lateral (telencephalic) versus fourth (hindbrain) plexus. We find that positional identities mouse, macaque, human plexi derive expression domains parallel their axial tissues origin. then show molecular heterogeneity between telencephalic...