A5045062494- Advanced Breast Cancer Therapies
- Biotin and Related Studies
- Peptidase Inhibition and Analysis
- Adenosine and Purinergic Signaling
- Biochemical and Molecular Research
- bioluminescence and chemiluminescence research
- Ferroptosis and cancer prognosis
- Advanced Proteomics Techniques and Applications
- HER2/EGFR in Cancer Research
- Cancer Immunotherapy and Biomarkers
- Mass Spectrometry Techniques and Applications
- Medical Imaging Techniques and Applications
- Monoclonal and Polyclonal Antibodies Research
- Bioinformatics and Genomic Networks
- Analytical Chemistry and Chromatography
- Cancer, Lipids, and Metabolism
- Microtubule and mitosis dynamics
- Radiopharmaceutical Chemistry and Applications
- Ion-surface interactions and analysis
- Computational Drug Discovery Methods
- DNA and Nucleic Acid Chemistry
- Protein Degradation and Inhibitors
- RNA modifications and cancer
- Steroid Chemistry and Biochemistry
- PI3K/AKT/mTOR signaling in cancer
Baylor College of Medicine
2022-2023
Florida State University
2017-2018
Lawrence Livermore National Laboratory
2007
University of California, Davis
2007
Drexel University
2007
Ion mobility spectrometry-mass spectrometry (IMS-MS) determines momentum transfer cross sections of ions to elucidate their structures. Recent IMS methods employ electrodynamic fields or nonstationary buffer gases separate ions. These require a calibration procedure determine ion mobilities from the experimental data. This applies in particular trapped (TIMS), novel method with reported high resolving powers. Here, we report first systematic assessment accuracy and limitations TIMS. Our data...
Abstract Transcriptionally active ESR1 fusions (ESR1-TAF) are a potent cause of breast cancer endocrine therapy (ET) resistance. ESR1-TAFs not directly druggable because the C-terminal estrogen/anti-estrogen–binding domain is replaced with translocated in-frame partner gene sequences that confer constitutive transactivation. To discover alternative treatments, mass spectrometry (MS)–based kinase inhibitor pulldown assay (KIPA) was deployed to identify kinases upregulated by diverse...
Structure elucidation by ion mobility spectrometry-mass spectrometry methods is based on the comparison of an experimentally measured momentum transfer cross-section to cross-sections calculated for model structures. Thus, it imperative that must be accurate. However, not fully understood how important accurately charge distribution analyte when calculating cross-sections. Here, we calculate and compare carbon clusters differ in mass, state, mode distribution, vary temperature polarizability...
Here we report the design, implementation, and initial use of an asymmetric steady-state continuous dual-nanospray ion source. This new source design consists two independently controlled continuously operating nanospray interfaces with funnel shaped counter electrodes. A mixing region combines ions from sources into a single beam in intermediate after extraction but before bulk pressure gradient vacuum interface. With this have achieved robust no loss duty cycle remarkable ionization...
Triple-negative breast cancer (TNBC) constitutes 10%-15% of all tumors. The current standard care is multiagent chemotherapy, which effective in only a subset patients. original objective this study was to deploy mass spectrometry (MS)-based kinase inhibitor pulldown assay (KIPA) identify kinases elevated non-pCR (pathologic complete response) cases for therapeutic targeting. Frozen optimal cutting temperature compound-embedded core needle biopsies were obtained from 43 patients with TNBC...
<p>The Supplementary Material contains a cover page, 8 Figures and their legends.</p>
<div>Abstract<p>Transcriptionally active ESR1 gene fusions (ESR1-TAF) are a potent cause of breast cancer endocrine therapy (ET) resistance. ESR1-TAFs not directly druggable because the C-terminal estrogen/anti-estrogen binding domain is replaced with translocated in-frame partner sequences that confer constitutive transactivation. To discover alternative treatments, mass spectrometry (MS)-based kinase inhibitor pulldown assay (KIPA) was deployed to identify kinases upregulated...
<p>The Supplementary Material contains a cover page, 8 Figures and their legends.</p>
<div>Abstract<p>Transcriptionally active ESR1 fusions (ESR1-TAF) are a potent cause of breast cancer endocrine therapy (ET) resistance. ESR1-TAFs not directly druggable because the C-terminal estrogen/anti-estrogen–binding domain is replaced with translocated in-frame partner gene sequences that confer constitutive transactivation. To discover alternative treatments, mass spectrometry (MS)–based kinase inhibitor pulldown assay (KIPA) was deployed to identify kinases upregulated...
ABSTRACT Transcription factor EB (TFEB) is a master regulator of lysosomal biogenesis and autophagy that plays key role in the regulation cellular clearance pathways. TFEB regulated via complex array post-translational modifications (PTMs), but exact molecular mechanism regulates stability has remained elusive. Here, we show levels are critically by defined phosphorylation-ubiquitination cascade. A human kinome screen identifies IKK (inhibitor κB kinase) as modifier, combination...
<p>Supplementary Figure 1</p>
<p>Supplementary Figure 6</p>
<p>Supplementary Figure 3</p>
<p>The relationship between the KIPA-based PBP signature score, immune scores, and checkpoint levels. <b>A,</b> Scatter plot shows correlation score mRNA-based scores (from ESTIMATE, Cibersort, xCell). EST: CS: xC: xCell. <b>B,</b> protein-based modulator stimulatory or inhibitory scores. <b>C,</b> PD-L1 CPSs from IHC staining. <b>D,</b> phosphoprotein levels.</p>
<p>The application of the KIPA in CPTAC-TNBC samples. <b>A,</b> Overview 43 pretreatment biopsy samples used this study (14 pCR and 29 non-pCR samples). The were accrued from patients with TNBC enrolled two clinical trials (NCT02547987 NCT02124902) who treated six cycles docetaxel carboplatin (<a href="#bib14" target="_blank">14</a>). pCR, RCB class, omics data availability, molecular subtypes obtained previous publication href="#bib16"...
<p>The prognosis effects of the KIPA-based PBP signature in METABRIC dataset. <b>A,</b> Forest plot shows HRs and <i>P</i> values for disease-specific survival associated with seven genes. HR 95% confidence intervals were based on categorizing TNBC samples using a median mRNA expression cutoff each gene or score Survival analysis was also performed clinical factors (lymph nodes number, tumor size, grade). Blue boxes indicate univariate analysis, red multivariate...
<p>GSEA of the PBP signature-correlated genes. <b>A,</b> Bar plot shows enriched Hallmark gene sets (FDR < 0.05) from GSEA KIPA-based signature score-correlated genes at protein levels. input was a ranked list signed −log<sub>10</sub><i>P</i>-values Pearson correlation between score and all measured by global proteomics in CPTAC-TNBC dataset. Pathways with positive NES (normalized enrichment score) were positively correlated score, while pathways...
<div><p>Triple-negative breast cancer (TNBC) constitutes 10%–15% of all tumors. The current standard care is multiagent chemotherapy, which effective in only a subset patients. original objective this study was to deploy mass spectrometry (MS)-based kinase inhibitor pulldown assay (KIPA) identify kinases elevated non-pCR (pathologic complete response) cases for therapeutic targeting. Frozen optimal cutting temperature compound–embedded core needle biopsies were obtained from 43...
<p>The prognosis effects of the KIPA-based PBP signature in METABRIC dataset. <b>A,</b> Forest plot shows HRs and <i>P</i> values for disease-specific survival associated with seven genes. HR 95% confidence intervals were based on categorizing TNBC samples using a median mRNA expression cutoff each gene or score Survival analysis was also performed clinical factors (lymph nodes number, tumor size, grade). Blue boxes indicate univariate analysis, red multivariate...
<p>The relationship between the KIPA-based PBP signature score, immune scores, and checkpoint levels. <b>A,</b> Scatter plot shows correlation score mRNA-based scores (from ESTIMATE, Cibersort, xCell). EST: CS: xC: xCell. <b>B,</b> protein-based modulator stimulatory or inhibitory scores. <b>C,</b> PD-L1 CPSs from IHC staining. <b>D,</b> phosphoprotein levels.</p>
<p>Supplementary Figure 5</p>
<p>Supplementary Figure 6</p>
<p>Supplementary Figure 7</p>
<p>GSEA of the PBP signature-correlated genes. <b>A,</b> Bar plot shows enriched Hallmark gene sets (FDR < 0.05) from GSEA KIPA-based signature score-correlated genes at protein levels. input was a ranked list signed −log<sub>10</sub><i>P</i>-values Pearson correlation between score and all measured by global proteomics in CPTAC-TNBC dataset. Pathways with positive NES (normalized enrichment score) were positively correlated score, while pathways...
<p>Differential protein analysis between pCR and non-pCR samples. <b>A,</b> Volcano plot shows results from differential samples with the KIPA. <i>X</i>-axis is log<sub>10</sub> fold change median value of for each protein. <i>Y</i>-axis −log<sub>10</sub><i>P</i>-value Wilcoxon rank-sum tests comparing levels in to Red blue points indicate most significant (<i>P</i> < 0.01) proteins, pink light (0.01...