A5047373757- Advanced Proteomics Techniques and Applications
- Genomics and Phylogenetic Studies
- Alzheimer's disease research and treatments
- Machine Learning in Bioinformatics
- Mass Spectrometry Techniques and Applications
- RNA modifications and cancer
- Cholinesterase and Neurodegenerative Diseases
- Neuroinflammation and Neurodegeneration Mechanisms
- Gene expression and cancer classification
- Genomics and Chromatin Dynamics
- Metabolomics and Mass Spectrometry Studies
- RNA and protein synthesis mechanisms
- Neuroscience and Neuropharmacology Research
- Glycosylation and Glycoproteins Research
- S100 Proteins and Annexins
- Computational Drug Discovery Methods
- Mosquito-borne diseases and control
- Pancreatic and Hepatic Oncology Research
- Enzyme Structure and Function
- Genetics, Bioinformatics, and Biomedical Research
- Advanced Biosensing Techniques and Applications
- 14-3-3 protein interactions
- Parkinson's Disease Mechanisms and Treatments
- Peroxisome Proliferator-Activated Receptors
- Pancreatic function and diabetes
Boston Children's Hospital
2018-2024
Harvard University
2018-2024
Hasso Plattner Institute
2022-2024
University of Potsdam
2022-2024
Wellcome Sanger Institute
2016-2022
Boston Children's Museum
2022
University of Cambridge
2016-2018
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...
Mouse models that overexpress human mutant Tau (P301S and P301L) are commonly used in preclinical studies of Alzheimer's Disease (AD) while several drugs showed therapeutic effects these mice, they were ineffective humans. This leads to the question which extent murine reflect pathology on molecular level.
Abstract Aggregation prone molecules, such as tau, form both historically well characterized fibrillar deposits (neurofibrillary tangles) and recently identified phosphate-buffered saline (PBS) extract species called proteopathic seeds. Both can cause normal endogenous tau to undergo templated misfolding. The relationship of these seeds the fibrils that define tau-related diseases is unknown. We aqueous extractable sarkosyl insoluble derived from human Alzheimer brain using mass spectrometry...
Characterizing perturbation of molecular pathways in congenital Zika virus (ZIKV) infection is critical for improved therapeutic approaches. Leveraging integrative systems biology, proteomics, and RNA-seq, we analyzed embryonic brain tissues from an immunocompetent, wild-type ZIKV mouse model. induced a robust immune response accompanied by the downregulation neurodevelopmental gene programs. We identified negative correlation between polyprotein abundance host cell cycle-inducing proteins....
Abstract Background Clinical studies have long observed that neurodegenerative disorders display a range of symptoms and pathological features and, in some cases, overlap, suggesting these diseases exist on spectrum. Dementia with Lewy Bodies (DLB), synucleinopathy, is prominent example, where symptomatic similarities tauopathy, Alzheimer’s disease, are observed. Although tau pathology has been DLB, the interplay between α-synuclein poorly understood at molecular level. Methods Quantitative...
Current tools for visualization and integration of proteomics with other omics datasets are inadequate large-scale studies capture only basic sequence identity information. Furthermore, the frequent reformatting annotations reference genomes required by these is known to be highly error prone. We developed PoGo mapping peptides identified through mass spectrometry overcome limitations. reduced runtime memory usage 85% 20%, respectively, exhibited overall superior performance over on...
Combining robust proteomics instrumentation with high-throughput enabling liquid chromatography (LC) systems (e.g., timsTOF Pro and the Evosep One system, respectively) enabled mapping proteomes of 1000s samples. Fragpipe is one few computational protein identification quantification frameworks that allows for time-efficient analysis such large data sets. However, it requires amounts power storage space leave even state-of-the-art workstations underpowered when comes to sets LC mass...
Improvements in LC-MS/MS methods and technology have enabled the identification of thousands modified peptides a single experiment. However, protein regulation by post-translational modifications (PTMs) is not binary, making to quantify modification extent crucial understanding role PTMs. Here, we introduce FLEXIQuant-LF, software tool for large-scale differentially quantification their without knowledge types involved. We developed FLEXIQuant-LF using label-free unmodified robust linear...
Motivation: Accurate quantitative information about the protein abundance is crucial for understanding a biological system and its dynamics. Protein commonly estimated using label-free, bottom-up mass spectrometry protocols. Here, proteins are digested into peptides before quantification via spectrometry. However, missing peptide values, which can make up more than 50% of all common issue. They result in then hinder accurate reliable downstream analyses. Results: To impute we propose...
Accurate quantitative information about protein abundance is crucial for understanding a biological system and its dynamics. Protein commonly estimated using label-free, bottom-up mass spectrometry (MS) protocols. Here, proteins are digested into peptides before quantification via MS. However, missing peptide values, which can make up more than 50% of all common issue. They result in then hinder accurate reliable downstream analyses.
Cross-talk between genes, transcripts, and proteins is the key to cellular responses; hence, analysis of molecular levels as distinct entities slowly being extended integrative studies enhance understanding dynamics within cells. Current tools for visualization integration proteomics with other omics datasets are inadequate large-scale studies. Furthermore, they only capture basic sequence identify, discarding post-translational modifications quantitation. To address these issues, we...
In liquid-chromatography–tandem-mass-spectrometry-based proteomics, information about the presence and stoichiometry of protein modifications is not readily available. To overcome this problem, we developed multiFLEX-LF, a computational tool that builds upon FLEXIQuant, which detects modified peptide precursors quantifies their modification extent by monitoring differences between observed expected intensities unmodified precursors. multiFLEX-LF relies on robust linear regression to...
Total pancreatectomy with islet autotransplantation (TPIAT) is a surgical option for refractory chronic pancreatitis-related pain. Despite the known clinical implications of TPIAT, molecular effects remain poorly investigated. We performed first hypothesis-generating study urinary proteome before and after TPIAT.Twenty-two patients eligible TPIAT were prospectively enrolled. Urine samples collected week 12 to 18 months TPIAT. The urine prepared bottom-up label-free quantitative proteomics...
Abstract Improvements in LC-MS/MS methods and technology have enabled the identification of thousands modified peptides a single experiment. However, protein regulation by post-translational modifications (PTMs) is not binary, making to quantify modification extent crucial understanding role PTMs. Here, we introduce FLEXIQuant-LF, software tool for large-scale differentially quantification their without prior knowledge type modification. We developed FLEXIQuant-LF using label-free unmodified...
APOE is the strongest genetic risk factor for late-onset Alzheimer’s disease. ApoE exacerbates tau-associated neurodegeneration by driving microglial activation. However, how apoE regulates activation and whether targeting therapeutically beneficial in tauopathy unclear. Here we show that overexpressing a low-density lipoprotein receptor (LDLR) transgene P301S tau transgenic mice markedly reduces brain ameliorates pathology neurodegeneration. specifically interacts with high-molecular-weight...
Abstract Current tools for visualization and integration of proteomics with other omics datasets are inadequate large-scale studies capture only basic sequence identity information. We developed PoGo mapping peptides identified through mass spectrometry to a reference genome overcome these limitations. exhibited superior performance over on benchmarking human tissue cancer phosphoproteome datasets. Additionally, extended functionality enables representation single nucleotide variants,...
Cross-talk between genes, transcripts, and proteins is the key to cellular responses; hence, analysis of molecular levels as distinct entities slowly being extended integrative studies enhance understanding dynamics within cells. Current tools for visualization integration proteomics with other omics datasets are inadequate large-scale studies. Furthermore, they only capture basic sequence identify, discarding post-translational modifications quantitation. To address these issues, we...
Abstract Background: Mouse models that overexpress human mutant Tau (P301S and P301L) are commonly used in preclinical studies of Alzheimer’s Disease (AD) while several drugs showed therapeutic effects these mice, they were ineffective humans. This leads to the question which extent murine reflect pathology on molecular level. Methods: We isolated pathological species from two common AD mouse during different stages disease characterized modification landscape aggregated using targeted...