A5018484860- Mass Spectrometry Techniques and Applications
- Advanced Proteomics Techniques and Applications
- RNA and protein synthesis mechanisms
- Analytical Chemistry and Chromatography
- RNA Research and Splicing
- Ion-surface interactions and analysis
- Protein Structure and Dynamics
- Single-cell and spatial transcriptomics
- RNA modifications and cancer
- Extracellular vesicles in disease
- Metabolomics and Mass Spectrometry Studies
- Genomics and Chromatin Dynamics
- Reproductive tract infections research
- Pancreatic function and diabetes
- Cervical Cancer and HPV Research
- Molecular Biology Techniques and Applications
- Ubiquitin and proteasome pathways
- Cellular transport and secretion
- Enzyme Structure and Function
- Connexins and lens biology
- Genomics and Phylogenetic Studies
- Analytical chemistry methods development
- Biotin and Related Studies
- Neuroscience and Neuropharmacology Research
- Glycosylation and Glycoproteins Research
Harvard University
2016-2025
Harvard University Press
2014-2025
Novel (United States)
2023-2024
Inspire
2023-2024
Gates Foundation
2024
Northeastern University
2020
Universidad del Noreste
2020
Center for Systems Biology
2008-2017
Boston Children's Hospital
2005-2008
Boston University
2003-2006
Some exciting biological questions require quantifying thousands of proteins in single cells. To achieve this goal, we develop Single Cell ProtEomics by Mass Spectrometry (SCoPE-MS) and validate its ability to identify distinct human cancer cell types based on their proteomes. We use SCoPE-MS quantify over a thousand differentiating mouse embryonic stem The single-cell proteomes enable us deconstruct populations infer protein abundance relationships. Comparison between transcriptomes...
Evolving lineages face a constant intracellular threat: most new coding sequence mutations destabilize the folding of encoded protein. Misfolded proteins form insoluble aggregates and are hypothesized to be intrinsically cytotoxic. Here, we experimentally isolate fitness cost caused by toxicity misfolded proteins. We exclude other costs protein misfolding, such as loss functional or attenuation growth-limiting synthesis resources, comparing growth rates budding yeast expressing folded...
Understanding the regulation and structure of ribosomes is essential to understanding protein synthesis its dysregulation in disease. While are believed have a fixed stoichiometry among their core ribosomal proteins (RPs), some experiments suggest more variable composition. Testing such variability requires direct precise quantification RPs. We used mass spectrometry directly quantify RPs across monosomes polysomes mouse embryonic stem cells (ESC) budding yeast. Our data show that wild-type...
Electron-capture dissociation (ECD) is a new fragmentation technique that utilizes ion–electron recombination reactions. The latter have parallels in other research fields; revealing these helps to understand the ECD mechanism. An overview given of ECD-related phenomena and history discovery development. Current views on mechanism are discussed using both published examples.
The existence of nonannotated protein-coding human short open reading frames (sORFs) has been revealed through the direct detection their sORF-encoded polypeptide (SEP) products. discovery novel SEPs increases size genome and proteome provides insights into molecular biology mammalian cells, such as prevalent usage non-AUG start codons. Through modifications existing SEP-discovery workflow, we discover an additional 195 in K562 cells extend this methodology to identify cell lines tissue for...
Signaling pathways can induce different dynamics of transcription factor (TF) activation. We explored how TFs process signaling inputs to generate diverse dynamic responses. The budding yeast general stress-responsive TF Msn2 acted as a tunable signal processor that could track, filter, or integrate signals in an input-dependent manner. This processing appears originate from dual regulation both nuclear import and export by phosphorylation, mutants with one form sustained only...
Fermenting glucose in the presence of enough oxygen to support respiration, known as aerobic glycolysis, is believed maximize growth rate. We observed increasing glycolysis during exponential growth, suggesting additional physiological roles for glycolysis. investigated such yeast batch cultures by quantifying O2 consumption, CO2 production, amino acids, mRNAs, proteins, posttranslational modifications, and stress sensitivity course nine doublings at constant During this course, cells a...
Brain in vitro models are critically important to developing our understanding of basic nervous system cellular physiology, potential neurotoxic effects chemicals, and specific mechanisms many disease states. In this study, we sought address key shortcomings current brain models: the scarcity comparative data for cells originating from distinct regions lack multiregional models. We demonstrated that rat neurons different exhibit unique profiles regarding their cell composition, protein...
Endothelial extracellular vesicles containing cardioprotective proteins rescue engineered human cardiac tissue in an ischemia-reperfusion injury model.
A major limitation to applying quantitative LC-MS/MS proteomics small samples, such as single cells, are the losses incured during sample cleanup. To relieve this limitation, we developed a Minimal ProteOmic Preparation (mPOP) method for culture-grown mammalian cells. mPOP obviates cleanup and thus eliminates cleanup-related while expediting preparation simplifying its automation. Bulk SILAC samples processed by or conventional urea-based methods indicated that results in complete cell lysis...
Abstract The molecular characterization of extracellular vesicles (EVs) has revealed a great heterogeneity in their composition at cellular and tissue level. Current isolation methods fail to efficiently separate EV subtypes for proteomic functional analysis. aim this study was develop reproducible scalable workflow increase the yield purity preparations. Through combination polymer‐based precipitation size exclusion chromatography (Pre‐SEC), we analyzed two subsets EVs based on CD9, CD63...
Tissue-specific stem cells persist for a lifetime and can differentiate to maintain homeostasis or transform initiate cancer. Despite their importance, there are no described quality assurance mechanisms newly formed cells. We observed intimate specific interactions between macrophages nascent blood in zebrafish embryos. Macrophage frequently led either removal of cytoplasmic material cell division complete engulfment death. Stressed were marked by surface Calreticulin, which stimulated...
Extracellular vesicles (EVs) are released by all cells into biofluids such as plasma. The separation of EVs from highly abundant free proteins and similarly sized lipoproteins remains technically challenging. We developed a digital ELISA assay based on Single Molecule Array (Simoa) technology for ApoB-100, the protein component several lipoproteins. Combining this ApoB-100 with previously Simoa assays albumin three tetraspanin found (Ter-Ovanesyan, Norman et al., 2021), we were able to...
Abstract Modulation of the cervix by steroid hormones and commensal microbiome play a central role in health female reproductive tract. Here we describe organ-on-a-chip (Organ Chip) models that recreate human cervical epithelial-stromal interface with functional epithelial barrier production mucus biochemical hormone-responsive properties similar to living cervix. When Cervix Chips are populated optimal healthy versus dysbiotic microbial communities (dominated Lactobacillus crispatus...
Two known phenanthroindolizidine alkaloids, (-)-(R)-13aalpha-antofine (1) and (-)-(R)-13aalpha-6-O-desmethylantofine (2), two new natural products, (-)-(R)-13aalpha-secoantofine (3) (-)-(R)-13aalpha-6-O-desmethylsecoantofine (4), were isolated from Cynanchum vincetoxicum. The structures of all compounds established by means NMR methods including COSY, NOESY, HSQC, HMBC experiments, supported HRMS optical rotation data. Cytotoxic activity the three other alkaloids previously Tylophora...