A5005061089- Ubiquitin and proteasome pathways
- Advanced Proteomics Techniques and Applications
- Metabolomics and Mass Spectrometry Studies
- Alzheimer's disease research and treatments
- Epigenetics and DNA Methylation
- Autophagy in Disease and Therapy
- Mitochondrial Function and Pathology
- Bioinformatics and Genomic Networks
- Mass Spectrometry Techniques and Applications
- RNA Research and Splicing
- Protein Degradation and Inhibitors
- RNA modifications and cancer
- Cancer, Hypoxia, and Metabolism
- Genomics and Chromatin Dynamics
- Endoplasmic Reticulum Stress and Disease
- Cancer-related gene regulation
- Genetics and Neurodevelopmental Disorders
- Glycosylation and Glycoproteins Research
- Cellular transport and secretion
- Cancer-related Molecular Pathways
- Neuroblastoma Research and Treatments
- Genetic Neurodegenerative Diseases
- Acute Lymphoblastic Leukemia research
- Acute Myeloid Leukemia Research
- Cancer-related molecular mechanisms research
St. Jude Children's Research Hospital
2016-2025
Zhuzhou Central Hospital
2022-2024
Central South University
2022-2024
Proteogenomics Research Institute for Systems Medicine
2019
Memphis Health Center
2019
Children's Research Hospital
2019
Emory University
2004-2012
Emory and Henry College
2011
Massachusetts General Hospital
2010
Institute of Human Genetics
2010
Highly complex protein mixtures can be directly analyzed after proteolysis by liquid chromatography coupled with tandem mass spectrometry (LC−MS/MS). In this paper, we have utilized the combination of strong cation exchange (SCX) and reversed-phase (RP) to achieve two-dimensional separation prior MS/MS. One milligram whole yeast was proteolyzed separated SCX (2.1 mm i.d.) fraction collection every minute during an 80-min elution. Eighty fractions were reduced in volume then re-injected via...
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,...
Despite progress in defining genetic risk for psychiatric disorders, their molecular mechanisms remain elusive. Addressing this, the PsychENCODE Consortium has generated a comprehensive online resource adult brain across 1866 individuals. The contains ~79,000 brain-active enhancers, sets of Hi-C linkages, and topologically associating domains; single-cell expression profiles many cell types; quantitative-trait loci (QTLs); further QTLs associated with chromatin, splicing, cell-type...
P-TEFb is a key regulator of the process controlling processivity RNA polymerase II and possesses kinase activity that can phosphorylate carboxy-terminal domain largest subunit II. Here we report cloning small Drosophila finding it encodes Cdc2-related protein kinase. Sequence comparison suggests with 72% identity, PITALRE, could be human homolog protein. Functional homology was suggested by transcriptional analysis an promoter HeLa nuclear extract depleted PITALRE. Because lost ability to...
The positively charged lysine residue plays an important role in protein folding and functions. Neutralization of the charge often has a profound impact on substrate proteins. Accordingly all known post-translational modifications at have pivotal roles cell physiology pathology. Here we report discovery two novel, vivo histones, propionylation butyrylation. We confirmed, by vitro labeling peptide mapping mass spectrometry, that previously acetyltransferases, p300 CREB-binding protein, could...
The entry of RNA polymerase II into a productive mode elongation is controlled, in part, by the postinitiation activity positive transcription factor b (P-TEFb) (Marshall, N. F., and Price, D. H. (1995) J. Biol. Chem. 270, 12335-12338). We report here that removal carboxyl-terminal domain (CTD) large subunit abolishes elongation. Correspondingly, we found P-TEFb can phosphorylate CTD pure II. Furthermore, when an early complex. Both function kinase are blocked drugs...
To identify novel inhibitors of transcriptional activation by the HIV Tat protein, we used a combination in vitro and vivo Tat-dependent transcription assays to screen >100,000 compounds. All compounds identified blocked stimulation elongation. Analysis panel structurally diverse indicated that their target is human homolog Drosophila positive elongation factor b (P-TEFb). Loss transactivation extracts depleted kinase subunit P-TEFb, PITALRE, was reversed addition partially purified...
The postsynaptic density (PSD) of central excitatory synapses plays a key role in signal transduction and contains high concentration glutamate receptors associated scaffold signaling proteins. We report here comprehensive analysis purified PSD fractions by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). identified 374 different proteins that copurified the structure discovered thirteen phosphorylated sites from eight These were classified into numerous functional...
TAR DNA-binding protein 43 (TDP-43) is associated with a spectrum of neurodegenerative diseases. Although TDP-43 resembles heterogeneous nuclear ribonucleoproteins, its RNA targets and physiological partners remain unknown. Here we identify from cortical neurons by immunoprecipitation followed deep sequencing (RIP-seq). The canonical binding site (TG)n 55.1-fold enriched, moreover, variant adenine in the middle, (TG)nTA(TG)m, highly abundant among reads our RIP-seq library. can be divided...
Abstract The maturation of young neurons is regulated by complex mechanisms and dysregulation this process frequently found in neurodevepmental disorders. MicroRNAs have been implicated several steps neuronal including dendritic axonal growth, spine development, synaptogenesis. We demonstrate that one brain-enriched microRNA, miR-137, has a significant role regulating maturation. Overexpression miR-137 inhibits morphogenesis, phenotypic maturation, development both brain cultured primary...
The biological processes that are disrupted in the Alzheimer's disease (AD) brain remain incompletely understood. In this study, we analyzed proteomes of more than 1,000 tissues to reveal new AD-related protein co-expression modules were highly preserved across cohorts and regions. Nearly half modules, including significantly altered AD, not observed RNA networks from same regions, highlighting proteopathic nature AD. Two such AD-associated unique proteomic network included a module related...
Deposition of insoluble protein aggregates is a hallmark neurodegenerative diseases. The universal presence β-amyloid and tau in Alzheimer’s disease (AD) has facilitated advancement the amyloid cascade hypotheses that have dominated AD pathogenesis research therapeutic development. However, underlying etiology remains to be fully elucidated. Here we report comprehensive study human brain-insoluble proteome by mass spectrometry. We identify 4,216 proteins, among which 36 proteins accumulate...