A5079679478- Cancer Mechanisms and Therapy
- Chromatin Remodeling and Cancer
- CAR-T cell therapy research
- Protein Degradation and Inhibitors
- Cancer Research and Treatments
- Virus-based gene therapy research
- Cancer, Hypoxia, and Metabolism
- Extracellular vesicles in disease
- Acute Myeloid Leukemia Research
- Lung Cancer Treatments and Mutations
- RNA modifications and cancer
- RNA Research and Splicing
- Pesticide and Herbicide Environmental Studies
- Lymphoma Diagnosis and Treatment
- Amino Acid Enzymes and Metabolism
- Cancer Genomics and Diagnostics
- Cancer-related gene regulation
- Glioma Diagnosis and Treatment
- interferon and immune responses
- Peptidase Inhibition and Analysis
- Advanced Proteomics Techniques and Applications
- Ubiquitin and proteasome pathways
- MicroRNA in disease regulation
- Molecular Biology Techniques and Applications
- Weed Control and Herbicide Applications
Translational Genomics Research Institute
2016-2025
City of Hope
2021-2025
City Of Hope National Medical Center
2022-2024
Massachusetts General Hospital
2024
Harvard University
2024
Beckman Research Institute
2023
Phoenix (United States)
2023
Baylor University
2018
Laboratoire National de Santé
2010-2011
ABSTRACT Biofluid‐accessible extracellular vesicles (EVs) may represent a new means to improve the sensitivity and specificity of detecting disease. However, current methods isolate EVs encounter challenges when they are used select specific populations. Moreover, it has been difficult comprehensively characterize heterogeneous EV populations at single vesicle level. Here, we robustly assessed from cultured cell lines via nanoparticle tracking analysis, proteomics, transcriptomics,...
Cell-free DNA (cfDNA) in urine is a promising analyte for noninvasive diagnostics. However, cfDNA highly fragmented. Whether characteristics of these fragments reflect underlying genomic architecture unknown. Here, we characterized fragmentation patterns using whole-genome sequencing. Size distribution showed multiple strong peaks between 40 and 120 base pairs (bp) with modal size 81- sharp 10-bp periodicity, suggesting transient protection from complete degradation. These properties were...
Abstract Background Herbicides are environmental contaminants that have gained much attention due to the potential hazards they pose human health. Glyphosate, active ingredient in many commercial herbicides, is most heavily applied herbicide worldwide. The recent rise glyphosate application corn and soy crops correlates positively with increased death rates Alzheimer’s disease other neurodegenerative disorders. Glyphosate has been shown cross blood–brain barrier vitro models, but yet be...
The choroid plexus (ChP) produces and is bathed in the cerebrospinal fluid (CSF), which aging Alzheimer's disease (AD) shows extensive proteomic alterations including evidence of inflammation. Considering inflammation hampers functions involved tissues, CSF abnormalities reported these conditions are suggestive ChP injury. Indeed, several studies document damage AD, nevertheless remains to be systematically characterized. We here report that changes elicited by AD consistent with a perturbed...
Abstract Current anticancer therapies cannot eliminate all cancer cells, which hijack normal arginine methylation as a means to promote their maintenance via unknown mechanisms. Here we show that targeting protein N -methyltransferase 9 (PRMT9), whose activities are elevated in blasts and leukemia stem cells (LSCs) from patients with acute myeloid (AML), eliminates disease cancer-intrinsic mechanisms cancer-extrinsic type I interferon (IFN)-associated immunity. PRMT9 ablation AML decreased...
Abstract The plasma membrane is enriched for receptors and signaling proteins that are accessible from the extracellular space pharmacological intervention. Here we conducted a series of CRISPR screens using human cell surface proteome integrin family libraries in multiple cancer models. Our results identified ITGAV (integrin αV) its heterodimer partner ITGB5 β5) as essential α/β pair expansion. High-density gene tiling further pinpointed integral pocket within β-propeller domain αVβ5...
Mutations in Matrin 3 have recently been linked to ALS, though the mechanism that induces disease these patients is unknown. To define protein interactome of wild-type and ALS-linked MATR3 mutations, we performed immunoprecipitation followed by mass spectrometry using NSC-34 cells expressing human or mutant 3. Gene ontology analysis identified a novel role for mRNA transport centered on proteins TRanscription EXport (TREX) complex, known function biogenesis nuclear export. mutations led its...
Abstract Purpose: Small cell carcinoma of the ovary, hypercalcemic type (SCCOHT) is a rare, aggressive ovarian cancer in young women that universally driven by loss SWI/SNF ATPase subunits SMARCA4 and SMARCA2. A great need exists for effective targeted therapies SCCOHT. Experimental Design: To identify underlying therapeutic vulnerabilities SCCOHT, we conducted high-throughput siRNA drug screens. Complementary proteomics approaches profiled kinases inhibited ponatinib. Ponatinib was tested...
Abstract Diffuse large B-cell lymphoma (DLBCL) exhibits significant genetic heterogeneity which contributes to drug resistance, necessitating development of novel therapeutic approaches. Pharmacological inhibitors cyclin-dependent kinases (CDK) demonstrated pre-clinical activity in DLBCL, however many stalled clinical development. Here we show that AZD4573, a selective inhibitor CDK9, restricted growth DLBCL cells. CDK9 inhibition (CDK9i) resulted rapid changes the transcriptome and...
Abstract The robust detection of disease-associated splice events from RNAseq data is challenging due to the potential confounding effect gene expression levels and often limited number patients with relevant data. Here we present a novel statistical approach splicing outlier differential analysis. Our tests for differences in percentages sequence reads representing local events. We describe software package called Bisbee which can predict protein-level alterations, key feature lacking many...
Background: Glyphosate is the most commonly used herbicide in world and purported to have a variety of health effects, including endocrine disruption an elevated risk several types cancer. Blood DNA methylation has been shown be associated with many other environmental exposures, but our knowledge, no studies date examined association between blood glyphosate exposure. Objective: We conducted epigenome-wide study identify loci urinary its metabolite aminomethylphosphonic acid (AMPA) levels....
We examined small and long transcriptomics in skeletal muscle serum-derived extracellular vesicles before after a single exposure to traditional combined exercise (TRAD) high-intensity tactical training (HITT). Across 40 young adults, we found more consistent protein-coding gene responses TRAD, whereas HITT elicited differential expression of microRNA enriched brain regions. Follow-up analysis revealed relationships temporal dynamics across transcript networks, highlighting potential avenues...
Abstract SMARCA4 (BRG1) and SMARCA2 (BRM) are the two paralogous ATPases of SWI/SNF chromatin remodeling complexes frequently inactivated in cancers. Cells deficient either ATPase have been shown to depend on remaining counterpart for survival. Contrary this paralog synthetic lethality, concomitant loss SMARCA4/2 occurs a subset cancers associated with very poor outcomes. Here, we uncover that SMARCA4/2-loss represses expression glucose transporter GLUT1, causing reduced uptake glycolysis...
The DNA methyltransferase activity of DNMT1 is vital for genomic maintenance methylation. We report here that function regulated by O-GlcNAcylation, a protein modification sensitive to glucose levels, and elevated O-GlcNAcylation from high environment leads alterations the epigenome. Using mass spectrometry complementary alanine mutation experiments, we identified S878 as major residue O-GlcNAcylated on human DNMT1. Functional studies in mouse cells further revealed DNMT1-S878 results an...
Abstract The mechanisms underlying the transformation of chronic myeloid leukemia (CML) from phase (CP) to blast crisis (BC) are not fully elucidated. Here, we show lower levels miR-142 in CD34 + CD38 − blasts BC CML patients than those CP patients, suggesting that deficit is implicated evolution. Thus, create knockout (i.e., −/− BCR-ABL ) mice, which develop and die sooner wt +/+ instead remain CML. Leukemic stem cells (LSCs) mice recapitulate phenotype congenic recipients, supporting LSC...
Small cell carcinoma of the ovary, hypercalcemic type (SCCOHT) is a rare and aggressive form ovarian cancer. SCCOHT tumors have inactivating mutations in SMARCA4 (BRG1), one two mutually exclusive ATPases SWI/SNF chromatin remodeling complex. To address role that BRG1 loss plays tumorigenesis, we performed integrative multi-omic analyses lines +/- reexpression. reexpression induced gene protein signature similar to an epithelial gained accessibility sites correlated with other originating...
Cytoplasmic stress granules (SGs) are dynamic foci containing translationally arrested mRNA and RNA-binding proteins (RBPs) that form in response to a variety of cellular stressors. It has been debated SGs may evolve into cytoplasmic inclusions observed many neurodegenerative diseases. Recent studies have examined the SG proteome by interrogating interactome G3BP1. However, it is widely accepted multiple baits required capture full proteome. To gain further insight proteome, we employed...
Background: Obesity and diabetes are associated with elevated free fatty acids like palmitic acid (PA), which promote chronic inflammation impaired resolution cardiometabolic disorders. Long noncoding RNAs (lncRNAs) implicated in inflammatory processes; however, their roles PA-regulated unclear. Methods: We performed RNA-sequencing analysis to identify coding genes novel lncRNAs CD14 + monocytes from healthy volunteers. investigated the regulation function of an uncharacterized PA-induced...
Abstract Objective Amyotrophic lateral sclerosis (ALS) is a heterogeneous disease with complex etiology that lacks biomarkers predicting progression. The objective of this study was to use longitudinal cerebrospinal fluid (CSF) samples identify distinguish fast progression (FP) from slow (SP) and assess their temporal response. Methods We utilized mass spectrometry (MS)‐based proteomics candidate using CSF discovery cohort SP FP ALS patients. Immunoassays were used quantify validate levels...