R. Reid Townsend
A5044189301- Advanced Proteomics Techniques and Applications
- Acute Myeloid Leukemia Research
- Cancer Genomics and Diagnostics
- Mass Spectrometry Techniques and Applications
- Acute Lymphoblastic Leukemia research
- RNA modifications and cancer
- Protein Degradation and Inhibitors
- Ubiquitin and proteasome pathways
- Molecular Biology Techniques and Applications
- Metabolomics and Mass Spectrometry Studies
- Parasite Biology and Host Interactions
- Glycosylation and Glycoproteins Research
- Receptor Mechanisms and Signaling
- Biochemical and Molecular Research
- Monoclonal and Polyclonal Antibodies Research
- Ion channel regulation and function
- Lung Cancer Treatments and Mutations
- Bioinformatics and Genomic Networks
- Peptidase Inhibition and Analysis
- Advanced Biosensing Techniques and Applications
- Cancer-related Molecular Pathways
- RNA regulation and disease
- Parasites and Host Interactions
- RNA Research and Splicing
- Neuroscience and Neuropharmacology Research
Washington University in St. Louis
2016-2025
University of Health Sciences and Pharmacy
2023
Saint Louis University
2020
Cancer Institute (WIA)
2016
Fred Hutch Cancer Center
2013
Cancer Clinic
2013
National Cancer Institute
2011-2013
Pacific Northwest National Laboratory
2013
Broad Institute
2013
Vanderbilt-Ingram Cancer Center
2013
The genetic alterations responsible for an adverse outcome in most patients with acute myeloid leukemia (AML) are unknown.Using massively parallel DNA sequencing, we identified a somatic mutation DNMT3A, encoding methyltransferase, the genome of cells from patient AML normal karyotype. We sequenced exons DNMT3A 280 additional de novo to define recurring mutations.A total 62 281 (22.1%) had mutations that were predicted affect translation. 18 different missense mutations, common which was...
Adoption of targeted mass spectrometry (MS) approaches such as multiple reaction monitoring (MRM) to study biological and biomedical questions is well underway in the proteomics community. Successful application depends on ability generate reliable assays that uniquely confidently identify target peptides a sample. Unfortunately, there wide range criteria being applied say an assay has been successfully developed. There no consensus what are acceptable little understanding impact variable...
The National Cancer Institute (NCI) Clinical Proteomic Tumor Analysis Consortium is applying the latest generation of proteomic technologies to genomically annotated tumors from Genome Atlas (TCGA) program, a joint initiative NCI and Human Research Institute. By providing fully integrated accounting DNA, RNA, protein abnormalities in individual tumors, these datasets will illuminate complex relationship between genomic cancer phenotypes, thus producing biologic insights as well wave novel...
For many years, basic and clinical researchers have taken advantage of the analytical sensitivity specificity afforded by mass spectrometry in measurement proteins. Clinical laboratories are now beginning to deploy these work flows as well. assays that use proteolysis generate peptides for protein quantification characterization, synthetic stable isotope-labeled internal standard central importance. No general recommendations currently available surrounding spectrometric assays.The Proteomic...
Normal human luminal and myoepithelial breast cells separately purified from a set of 10 reduction mammoplasties by using double antibody magnetic affinity cell sorting Dynabead immunomagnetic technique were used in two-dimensional gel proteome studies. A total 43,302 proteins detected across the 20 samples, master image for each type comprising 1,738 unique was derived. Differential analysis identified 170 that elevated 2-fold or more between two types, 51 these annotated tandem mass...
Proteins associated with cancer cell plasma membranes are rich in known drug and antibody targets as well other proteins to play key roles the abnormal signal transduction processes required for carcinogenesis. We describe here a proteomics process that comprehensively annotates protein content of breast tumor defines clinical relevance such proteins. Tumor-derived lines were used ensure an enrichment cell-specific membrane because it is difficult purify cells then obtain good preparations...
Nucleophosmin (NPM) (B23) is an essential protein in mouse development and cell growth; however, it has been assigned numerous roles very diverse cellular processes.Here, we present a unified mechanism for NPM's role NPM directs the nuclear export of both 40S 60S ribosomal subunits.NPM interacts with rRNA large small subunit proteins also colocalizes nucleolus, nucleus, cytoplasm.The transduction shuttlingdefective mutants or loss Npm1 inhibited subunits, reduced available pool cytoplasmic...
Insulin is both a hormone regulating energy metabolism and growth factor. We others have shown that physiological doses of insulin initiate complex signals in primary human mouse β-cells, but the functional significance insulin's effects on this cell type remains unclear. In present study, role β-cell apoptosis was examined. Exogenous completely prevented induced by serum withdrawal when given at picomolar or low nanomolar concentrations not higher concentrations, indicating are...
Obesity is a principal risk factor for type 2 diabetes, and elevated fatty acids reduce β-cell function survival. An unbiased proteomic screen was used to identify targets of palmitate in death. The most significantly altered protein both human islets MIN6 β-cells treated with carboxypeptidase E (CPE). Palmitate reduced CPE levels within h, preceding endoplasmic reticulum (ER) stress cell death, by mechanism involving translocation Golgi lysosomal degradation. metabolism Ca 2+ flux were also...
Abstract Recent advances in mass spectrometry (MS) have enabled extensive analysis of cancer proteomes. Here, we employed quantitative proteomics to profile protein expression across 24 breast patient-derived xenograft (PDX) models. Integrated proteogenomic shows positive correlation between measurements from transcriptomic and proteomic analyses; further, gene expression-based intrinsic subtypes are largely re-capitulated using non-stromal markers. Proteogenomic also validates a number...
Coexpression of mRNAs under multiple conditions is commonly used to infer cofunctionality their gene products despite well-known limitations this "guilt-by-association" (GBA) approach. Recent advancements in mass spectrometry-based proteomic technologies have enabled global expression profiling at the protein level; however, whether proteome data can outperform transcriptome for coexpression based function prediction has not been systematically investigated. Here, we address question by...
Improvements in mass spectrometry (MS)-based peptide sequencing provide a new opportunity to determine whether polymorphisms, mutations, and splice variants identified cancer cells are translated. Herein, we apply proteogenomic data integration tool (QUILTS) illustrate protein variant discovery using whole genome, transcriptome, global proteome datasets generated from pair of luminal basal-like breast-cancer-patient-derived xenografts (PDX). The sensitivity analysis for singe nucleotide...
Many gene products exhibit great structural heterogeneity because of an array modifications. These modifications are not directly encoded in the genomic template but often affect functionality proteins. Protein glycosylation plays a vital role proper protein functions. However, analysis glycoproteins has been challenging compared with other modifications, such as phosphorylation. Here, we perform integrated proteomic and glycoproteomic 83 prospectively collected high-grade serous ovarian...
Abstract We have developed a deep-scale proteome and phosphoproteome database from 44 representative acute myeloid leukemia (AML) patients the LAML TCGA dataset 6 healthy bone marrow–derived controls. After confirming data quality, we orthogonally validated several previously undescribed features of AML revealed by proteomic data. identified examples posttranscriptionally regulated proteins both globally (ie, in all samples) also with recurrent driver mutations. For example, samples IDH1/2...
Standardized, comprehensive platforms for the discovery of protease substrates have been extremely difficult to create. Screens specificity are now frequently based on cleavage patterns peptide substrates, which contain small recognition motifs that required scissile bond within an active site. However, these studies do not identify in vivo nor can they lead definition macromolecular features account biological proteases. To use properly folded proteins a proteomic screen we used 2D...
The Haemophilus influenzae HMW1 adhesin is a high-molecular weight protein that secreted by the bacterial two-partner secretion pathway and mediates adherence to respiratory epithelium, an essential early step in pathogenesis of H. disease. In recent work, we discovered glycoprotein undergoes N-linked glycosylation at multiple asparagine residues with simple hexose units rather than N-acetylated units, revealing unusual N-glycosidic linkage suggesting new glycosyltransferase activity....
Bottom-up proteomics relies on the use of proteases and is method choice for identifying thousands protein groups in complex samples. Top-down has been shown to be robust direct analysis small proteins offers a solution "peptide-to-protein" inference problem inherent with bottom-up approaches. Here, we describe first large-scale integration genomic, top-down proteomic data comparative patient-derived mouse xenograft models basal luminal B human breast cancer, WHIM2 WHIM16, respectively....