A5102918572- Advanced Proteomics Techniques and Applications
- Bioinformatics and Genomic Networks
- Metabolomics and Mass Spectrometry Studies
- Mass Spectrometry Techniques and Applications
- Alzheimer's disease research and treatments
- Endoplasmic Reticulum Stress and Disease
- RNA Research and Splicing
- Mitochondrial Function and Pathology
- Genomics and Phylogenetic Studies
- Gene expression and cancer classification
- RNA and protein synthesis mechanisms
- Advanced biosensing and bioanalysis techniques
- Intracerebral and Subarachnoid Hemorrhage Research
- Autophagy in Disease and Therapy
- Click Chemistry and Applications
- Ubiquitin and proteasome pathways
- Renal Transplantation Outcomes and Treatments
- Glycosylation and Glycoproteins Research
- Phosphodiesterase function and regulation
- Hematopoietic Stem Cell Transplantation
- T-cell and B-cell Immunology
- RNA regulation and disease
- RNA modifications and cancer
- Glioma Diagnosis and Treatment
- Genomics and Chromatin Dynamics
St. Jude Children's Research Hospital
2017-2025
Institute of Hematology & Blood Diseases Hospital
2024
Chinese Academy of Medical Sciences & Peking Union Medical College
2024
Heilongjiang University of Chinese Medicine
2017
Most genetic risk for psychiatric disease lies in regulatory regions, implicating pathogenic dysregulation of gene expression and splicing. However, comprehensive assessments transcriptomic organization diseased brains are limited. In this work, we integrated genotypes RNA sequencing brain samples from 1695 individuals with autism spectrum disorder (ASD), schizophrenia, bipolar disorder, as well controls. More than 25% the transcriptome exhibits differential splicing or expression,...
Based on amyloid cascade and tau hypotheses, protein biomarkers of different Aβ species in cerebrospinal fluid (CSF) blood/plasma/serum have been examined to correlate with brain pathology. Recently, unbiased proteomic profiling these human samples has initiated identify a large number novel AD biomarker candidates, but it is challenging define reliable candidates for subsequent large-scale validation. We present comprehensive strategy high confidence by integrating multiple proteomes AD,...
Murine models of Alzheimer's disease (AD) are crucial for elucidating mechanisms but have limitations in fully representing AD molecular complexities. Here we present the comprehensive, age-dependent brain proteome and phosphoproteome across multiple mouse amyloidosis. We identified shared pathways by integrating with human metadata prioritized components multi-omics analysis. Collectively, two commonly used (5xFAD APP-KI) replicate 30% protein alterations; additional genetic incorporation...
Blood-based protein measurement is a routine practice for detecting biomarkers in human disease. Comprehensive profiling of blood/plasma/serum proteome challenge due to an extremely large dynamic range, as exemplified by small subset highly abundant proteins. Antibody-based depletion these proteins alleviates the problem but introduces experimental variations. We aimed establish method direct undepleted serum and apply toward biomarker discovery Alzheimer's disease (AD), AD most common form...
Isobaric labeling quantification by mass spectrometry (MS) has emerged as a powerful technology for multiplexed large-scale protein profiling, but measurement accuracy in complex mixtures is confounded the interference from coisolated ions, resulting ratio compression. Here we report that compression can be essentially resolved combination of pre-MS peptide fractionation, MS2-based detection, and post-MS computational correction. To recapitulate complexity biological samples, pooled tandem...
Abstract High throughput omics approaches provide an unprecedented opportunity for dissecting molecular mechanisms in cancer biology. Here we present deep profiling of whole proteome, phosphoproteome and transcriptome two high-grade glioma (HGG) mouse models driven by mutated RTK oncogenes, PDGFRA NTRK1 , analyzing 13,860 proteins 30,431 phosphosites mass spectrometry. Systems biology identify numerous master regulators, including 41 kinases 23 transcription factors. Pathway activity...
Abstract Intracerebral hemorrhage (ICH) is a subtype of stroke that followed by primary and secondary brain injury. As result the injury, cell metabolism disrupted series stress responses are activated, such as endoplasmic reticulum (ER) unfolded protein response (UPR), leading to re-establishment homeostasis or death. an important mechanism homeostasis, autophagy has been widely studied, associations between autophagy, ER stress, UPR have also demonstrated. Whether these mechanisms...
Brain proteins altered in young APOE ε4 carriers are found decades later Alzheimer’s disease and present novel drug targets.
The transcription factor CTCF appears indispensable in defining topologically associated domain boundaries and maintaining chromatin loop structures within these domains, supported by numerous functional studies. However, acute depletion of globally reduces interactions but does not significantly alter transcription.
Proteome profiling is a powerful tool in biological and biomedical studies, starting with samples at bulk, single-cell, or single-cell-type levels. Reliable methods for extracting specific cell-type proteomes are need, especially the cells (e.g., neurons) that cannot be readily isolated. Here, we present an innovative proximity labeling (PL) strategy proteomics of mouse brain, which TurboID (an engineered biotin ligase) used to label almost all proteins cell type. This bypasses requirement...
To study the effect of scalp acupuncture (SA) on mitophagy signaling pathway in caudate nucleus Sprague-Dawley rats following intracerebral hemorrhage (ICH). An ICH model was established by injecting autologous arterial blood into 200 male rats, which were divided five groups: sham, ICH, 3-methyladenine group (3-MA, 30 mg/kg), SA, and SA+3-MA. Animals analyzed at 6 24 h as well 3 7 days. Composite neurological scale score significantly higher SA than group. Transmission electron microscopy...
Isobaric tandem mass tag (TMT) labeling is widely used in proteomics because of its high multiplexing capacity and deep proteome coverage. Recently, an expanded 16-plex TMT method has been introduced, which further increases the throughput proteomic studies. In this manuscript, we present optimized protocol for TMT-based deep-proteome profiling, including protein sample preparation, enzymatic digestion, reaction, two-dimensional reverse-phase liquid chromatography (LC/LC) fractionation,...
Many exceptional advances have been made in mass spectrometry (MS)-based proteomics, with particular technical progress liquid chromatography (LC) coupled to tandem (LC-MS/MS) and isobaric labeling multiplexing capacity. Here, we introduce a deep-proteomics profiling protocol that combines 10-plex tag (TMT) an extensive LC/LC-MS/MS platform, post-MS computational interference correction accurately quantitate whole proteomes. This includes the following main steps: protein extraction...
The linear sequence of amino acids in a protein folds into 3D structure to execute activity and function, but it is still challenging profile the at proteome scale. Here, we present method native tandem mass tag (TMT) profiling Lys accessibility its application investigate structural alterations human brain specimens Alzheimer's disease (AD). In this method, proteins are extracted under condition, labeled by TMT reagents, followed trypsin digestion peptide analysis using two-dimensional...
Abstract The integration of genomics and proteomics data (proteogenomics) holds the promise furthering in-depth understanding human disease. However, sample mix-up is a pervasive problem in proteogenomics because complexity processing. Here, we present pipeline for Sample Matching Proteogenomics (SMAP) to verify identity ensure integrity. SMAP infers sample-dependent protein-coding variants from quantitative mass spectrometry (MS), aligns MS-based proteomic samples with genomic by two...
<title>Abstract</title> Psychiatric disorders are highly heritable yet polygenetic, potentially involving hundreds of risk genes. Genome-wide association studies (GWAS) have identified genomic susceptibility loci for psychiatric disorders, but how these contribute to the underlying psychopathology and etiology remains elusive. Here we generated a deep human brain proteome by quantifying 11,672 proteins across 288 subjects using 11-plex tandem mass tag (TMT) coupled with two-dimensional...
Abstract Murine models of Alzheimer’s disease (AD) are crucial for elucidating mechanisms but have limitations in fully representing AD molecular complexities. We comprehensively profiled age-dependent brain proteome and phosphoproteome ( n > 10,000 both) across multiple mouse amyloidosis. identified shared pathways by integrating with human metadata, prioritized novel components multi-omics analysis. Collectively, two commonly used (5xFAD APP-KI) replicate 30% the protein alterations;...
<title>Abstract</title> Murine models of Alzheimer’s disease (AD) are crucial for elucidating mechanisms but have limitations in fully representing AD molecular complexities. We comprehensively profiled age-dependent brain proteome and phosphoproteome (n > 10,000 both) across multiple mouse amyloidosis. identified shared pathways by integrating with human metadata, prioritized novel components multi-omics analysis. Collectively, two commonly used (5xFAD APP-KI) replicate 30% the protein...