A5023248105- Advanced Proteomics Techniques and Applications
- Metabolomics and Mass Spectrometry Studies
- Cancer, Hypoxia, and Metabolism
- Mass Spectrometry Techniques and Applications
- Bioinformatics and Genomic Networks
- Radiomics and Machine Learning in Medical Imaging
- Molecular Biology Techniques and Applications
- Ubiquitin and proteasome pathways
- Breast Cancer Treatment Studies
- Epigenetics and DNA Methylation
- Erythropoietin and Anemia Treatment
- Ferroptosis and cancer prognosis
- Genomics and Chromatin Dynamics
- Cancer, Lipids, and Metabolism
- Cancer-related Molecular Pathways
- Pancreatic and Hepatic Oncology Research
- RNA modifications and cancer
- Ion-surface interactions and analysis
- Neural dynamics and brain function
- Folate and B Vitamins Research
- Advanced Breast Cancer Therapies
- Machine Learning and Data Classification
- Histone Deacetylase Inhibitors Research
- Cancer Genomics and Diagnostics
- Click Chemistry and Applications
Washington University in St. Louis
2023-2025
Framingham State University
2020-2024
Uniformed Services University of the Health Sciences
2022
Henry M. Jackson Foundation
2022
Windber Research Institute
2022
Berg (United States)
2021
Precision for Medicine (United States)
2021
Top-down proteomics is the study of intact proteins and their post-translational modifications with mass spectrometry. Historically, this field more challenging than its bottom-up counterpart because species are much bigger have a larger number possible combinations sequences modifications; thus, there great need for technological development. With improvements in instrumentation multiplicity fragmentation modes available, top-down quickly gaining popularity renewed attention on increasing...
ADP-ribosylation, characterized by the addition of adenosine diphosphate ribose, can occur in both monomeric (MARylation) and polymeric (PARylation) forms. Little is known about specific contributions MARylation PARylation to cellular processes due a lack tools for jointly investigating these individual We present novel mass spectrometry (MS)-based proteomics approach that preserves information native ADP-ribosylation form associated with modification site within single experiment. Our...
Abstract Protein arginylation is an essential posttranslational modification (PTM) catalyzed by arginyl-tRNA-protein transferase 1 (ATE1) in mammalian systems. Arginylation features a post-translational conjugation of arginyl to protein, making it extremely challenging differentiate from translational arginine residues with the same mass protein sequence. Here we present general activity-based profiling (ABAP) platform for unbiased discovery substrates and their precise sites. This method...
Histones are DNA binding proteins that allow for packaging of the into nucleus. They abundantly present across genome and thus serve as a major site epigenetic regulation through use post-translational modifications (PTMs). Aberrations in histone expression have been implicated variety human diseases focus disease etiology studies. A well-established method studying histones PTMs is chemical derivatization isolated followed by liquid chromatography mass spectrometry analysis. Using such an...
Abstract Cancer biomarker discovery is critically dependent on the integrity of biofluid and tissue samples acquired from study participants. Multi-omic profiling candidate protein, lipid, metabolite biomarkers confounded by timing fasting status sample collection, participant demographics treatment exposures population. Contamination hemoglobin, whether caused hemolysis during preparation or underlying red cell fragility, contributes 0–10 g/L extraneous protein to plasma, serum, Buffy coat...
Proteomic studies are typically conducted using flash-frozen (FF) samples utilizing tandem mass spectrometry (MS). However, FF specimens comprised of multiple cell types, making it difficult to ascertain the proteomic profiles specific cells. Conversely, OCT-embedded (Optimal Cutting Temperature compound) can undergo laser microdissection (LMD) capture and study types separately from mixture. In current study, we compared data obtained OCT determine if that stored processed differently...
The prefrontal cortex (PFC) is a region of the brain that in humans involved production higher-order functions such as cognition, emotion, perception, and behavior. Neurotransmission PFC produces by integrating information from other areas brain. At foundation neurotransmission, extension at functions, are an untold number coordinated molecular processes involving DNA sequence variants genome, RNA transcripts transcriptome, proteins proteome. These "multiomic" foundations poorly understood...
Abstract Arginylation installed by arginyltransferase 1 (ATE1) features an addition of arginine (Arg) to the reactive amino acids ( e . g ., Glu and Asp) at protein N -terminus or side chain. Systemic removal arginylation after ATE1 knockout (KO) in mouse models resulted heart defects leading embryonic lethality. The biological importance has motivated discovery sites on proteins using bottom-up approaches. While proteomics is powerful localizing peptide arginylation, it lacks ability...
Abstract Introduction: Classification of breast cancer can incorporate immunohistochemical (IHC) detection ER/PR/HER2/KI67 to stratify the subtypes. High throughput proteomics analysis allows for expansion biomarker discovery within We evaluated a cohort 109 tumors characterized as ER+ (Luminal A and Luminal B1; HER2+ ER low (1-10%) cases were excluded) compared ER-/HER2- tumors. Utilizing an integrated bioinformatics approach, we developed proteomic marker signature reclassify into...
Abstract Biomarker analysis is critically dependent on the quality of biofluid or tissue samples obtained from human research studies. Although proteomic, lipidomic, and metabolomic analyses can be dramatically impacted by time sample collection, fasting status, participant demographics, hemolysis status plasma, serum buffy coat a poorly understood confounder quality. Hemoglobin levels range between 0 - 10 g/L in (referred to as 1-4 plasma/serum 0-4 level coat) marker severity contamination...
Abstract Breast cancer (BrCA) therapeutic selection routinely incorporates clinicopathologic information along with immunohistochemistry (IHC) for ER/PR/HER2/Ki-67. However, this is incomplete and has shortcomings that are seen in clinical outcome differences even within the same subtype. Herein, we analyzed proteome of 116 HER2-negative primary BrCA samples subsequently validated a 34-proteogenomic signature 5,963 tumor from TCGA, METABRIC, GSE96058 demonstrated metabolic enrichment...
Abstract Introduction: In clinical practice, immunohistochemistry (IHC) is combined with clinicopathologic information to stratify patients into subtypes and guide treatment decisions. our mass spectrometry study of 116 breast cancers (BrCAs), we identified 34 significant proteins which provide additional prognostic information. This novel proteomic subtyping, combining IHC proteomics, separates HER2 negative (Her2-) BrCA Luminal-like TN-like subtypes. A subtype, luminal by proteomics (L/T),...
Abstract Ubiquitination is a conserved post translation modification involving covalent attachment of ubiquitin protein and known to regulate many biological processes, including proteasomal degradation. Three major families enzymes are involved in the regulation ubiquitination, activating enzyme E1, Ubiquitin conjugating E2 ligase E3. UBE2K an that was identified as anti-cancer drug target from BERG Interrogative Biology® platform, artificial intelligence multi-omics analytical method...
Abstract Background: Proteomic studies are typically conducted using flash-frozen (FF) samples utilizing tandem mass spectrometry. However, FF comprised of multiple cell types, making it difficult to ascertain the proteomic profiles specific cells. Conversely, OCT-embedded (Optimal Cutting Temperature compound) specimens can undergo laser microdissection (LMD) capture and study types separately from mixture. In current study, we compared data obtained OCT determine if that stored processed...
Abstract Introduction: Improving stratification of breast cancer (BC) patients based on molecular signatures for treatment responses and clinical outcomes is a critical unmet need. Currently, endocrine therapy first-line hormone receptor positive (HR+) BC. Chemotherapy added to with high-risk luminal In practice, levels Ki-67 are used distinguish tumors as low-risk A (LA) B (LB) adjuvant decisions. Herein, proteomic tumor assessment from ER-positive HER2-negative (ER+/HER2-) BC was utilized...
2059 Background: BPM 31510-IV is a drug-lipid conjugate nanodispersion containing oxidized Coenzyme Q10 (CoQ10) in clinical development for glioblastoma multiforme (GBM). In recently concluded Phase 1 study of (NCT03020602), addition to safety and tolerability, longitudinal pharmacodynamic samples (20 samples/cycle 28 days) were collected at various times patient’s refractory radiation, temozolomide, bevacizumab. Methods: Comprehensive multi-omic (proteomic, lipidomic, metabolomic) profiles...
Abstract Cancer biomarker discovery is critically dependent on the integrity of biofluid, and tissue samples acquired from study participants. Multi-omic profiling candidate protein, lipid, metabolite biomarkers confounded by timing fasting status sample collection, participant demographics treatment exposures population. Contamination hemoglobin, whether caused hemolysis during preparation or underlying red cell fragility, contributes 0 – 10 g/L extraneous protein to plasma, serum, Buffy...
Abstract Introduction: In the United States, breast cancer represents leading diagnosis among women and can readily be classified as a metabolic disease based on its distinct activity within tumor microenvironment. Compared to other omics technologies, extensive lipidomic metabolomic studies are lacking. Here in, we evaluated cohort of 109 tumors characterized ER+/HER2- ER-/HER2- immunohistochemistry (IHC) performed comprehensive structural lipidomic, signaling global analyses for an...
Abstract Cancer biomarker discovery is critically dependent on the integrity of biofluid, and tissue samples acquired from study participants. Multi-omic profiling candidate protein, lipid, metabolite biomarkers confounded by timing fasting status sample collection, participant demographics treatment exposures population. Contamination hemoglobin, whether caused hemolysis during preparation or underlying red cell fragility, contributes 0–10 g/L extraneous protein to plasma, serum, Buffy coat...