A5083563392- RNA regulation and disease
- RNA Research and Splicing
- RNA modifications and cancer
- Cancer-related molecular mechanisms research
- interferon and immune responses
- Cancer-related Molecular Pathways
- RNA and protein synthesis mechanisms
- Nuclear Structure and Function
- Ubiquitin and proteasome pathways
- DNA Repair Mechanisms
- Cancer Genomics and Diagnostics
- Cytokine Signaling Pathways and Interactions
- Lung Cancer Treatments and Mutations
- Virus-based gene therapy research
- BRCA gene mutations in cancer
- Immune Response and Inflammation
- Immune Cell Function and Interaction
- Adenosine and Purinergic Signaling
- Cholangiocarcinoma and Gallbladder Cancer Studies
- Cancer, Hypoxia, and Metabolism
- Genomics and Chromatin Dynamics
- Acute Myeloid Leukemia Research
- Multiple Myeloma Research and Treatments
- Peptidase Inhibition and Analysis
- Cell death mechanisms and regulation
Washington University in St. Louis
2014-2025
Molecular Oncology (United States)
2009-2025
Centre Hospitalier Universitaire de Reims
2020
Université de Reims Champagne-Ardenne
2020
University of Missouri–St. Louis
2016
Saint Louis University
2000-2006
Competition for nutrients like glucose can metabolically restrict T cells and contribute to their hyporesponsiveness during cancer. Metabolic adaptation the surrounding microenvironment is therefore key maintaining appropriate cell function. For instance, cancer use acetate as a substrate alternative fuel metabolism growth. Here, we show that rescues effector function in glucose-restricted CD8+ cells. Mechanistically, promotes histone acetylation chromatin accessibility enhances IFN-γ gene...
Nucleophosmin (NPM/B23) is a key regulator in the regulation of number processes including centrosome duplication, maintenance genomic integrity, and ribosome biogenesis. While mechanisms underlying NPM function are largely uncharacterized, loss results severe dysregulation developmental growth-related events. We show that utilizes conserved CRM1-dependent nuclear export sequence its amino terminus to enable shuttling between nucleolus/nucleus cytoplasm. In search trafficking targets, we...
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...
Nearly all patients with small cell lung cancer (SCLC) eventually relapse chemoresistant disease. The molecular mechanisms driving chemoresistance in SCLC remain un-characterized. Here, we describe whole-exome sequencing of paired tumor samples procured at diagnosis and from 12 patients, unpaired 18 additional patients. Multiple somatic copy number alterations, including gains ABCC1 deletions MYCL, MSH2, MSH6, are identifiable relapsed samples. Relapse also exhibit recurrent mutations loss...
The ARF tumor suppressor is widely regarded as an upstream activator of p53-dependent growth arrest and apoptosis.However, recent findings indicate that can also regulate the cell cycle in absence p53.In search p53-independent targets, we isolated nucleophosmin (NPM/B23), a protein show required for proliferation, novel binding protein.In response to hyperproliferative signals, upregulated, resulting nucleolar retention NPM concomitant arrest.The Mdm2 oncogene outcompetes NPM/B23 binding,...
The PA200 proteasome activator is a broadly expressed nuclear protein.Although how normally functions not fully understood, it has been suggested to be involved in the repair of DNA double-strand breaks (DSBs).The gene (Psme4) composed 45 coding exons spanning 108 kb on mouse chromosome 11.We generated null allele (PA200 ⌬ ) through Cre-loxP-mediated interchromosomal recombination after targeting loxP sites at either end locus.PA200 ⌬/⌬ mice are viable and have no obvious developmental...
The histone methyltransferase WHSC1 (also known as MMSET) is overexpressed in multiple myeloma (MM) a result of the t(4;14) chromosomal translocation and broad variety other cancers by unclear mechanisms. Overexpression did not transform wild-type or tumor-prone primary hematopoietic cells. We found that ACA11, an orphan box H/ACA class small nucleolar RNA (snoRNA) encoded within intron WHSC1, was highly expressed t(4;14)-positive MM cancers. ACA11 localized to nucleoli bound what we believe...
In this study, the anti-inflammatory actions of peroxisome proliferator-activated receptor (PPAR)-gamma agonists 15-deoxy-delta 12,14-prostaglandin J2 (15-d-delta 12,14-PGJ2) and troglitazone have been examined. Treatment RAW 264.7 cells CD-1 mouse peritoneal macrophages with lipopolysaccharide (LPS) + interferon-gamma (IFN-gamma) results in inducible nitric oxide synthase (iNOS), cyclooxygenase (COX-2) interleukin-1 (IL-1) expression, increased production oxide, release IL-1. a...
The ARF and p53 tumor suppressors are thought to act in a linear pathway prevent cellular transformation response various oncogenic signals. Here, we show that loss of leads an increase protein levels, which function limit the proliferation tumorigenicity p53-deficient cells by inhibiting IFN-β-STAT1-ISG15 signaling axis. Human triple-negative breast cancer (TNBC) samples with coinactivation exhibit high expression both STAT1 ISG15, TNBC cell lines sensitive depletion. We propose subsequent...
Abstract In response to virus infection or treatment with dsRNA, macrophages express the inducible form of cyclooxygenase-2 (COX-2) and produce proinflammatory prostaglandins. Recently, we have shown that NF-κB is required for encephalomyocarditis (EMCV)- dsRNA-stimulated COX-2 expression in mouse macrophages. The dsRNA-dependent protein kinase R not EMCV-stimulated expression, suggesting presence R-independent pathways regulation this antiviral gene. study, role MAPK macrophage (COX)-2 EMCV...
Triple-negative breast cancer (TNBC), lacking expression of estrogen, progesterone, and HER2 receptors, is aggressive lacks targeted treatment options. An RNA editing enzyme, adenosine deaminase acting on 1 (ADAR1), has been shown to play important roles in TNBC tumorigenesis. We posit that ADAR1 functions as a homeostatic factor protecting from internal external pressure, including metabolic stress. tested the hypothesis iron- dependent cell death pathway, ferroptosis, ADAR1-protected...
Alzheimer's disease (AD) disrupts behavioral circadian rhythms, but its effects on molecular rhythms in the human brain are poorly understood. Using single-nucleus RNA sequencing from post-mortem cortical samples, we informatically estimated relative phases of 409 persons with and without AD dementia. We then reconstructed expression profiles across cell types. While core clock were preserved AD, many cell-type specific outputs disrupted. Rhythms ribosomal biogenesis oxidative...
Abstract Triple-negative breast cancer (TNBC), lacking expression of estrogen, progesterone, and HER2 receptors, is aggressive lacks targeted treatment options. An RNA editing enzyme, adenosine deaminase acting on 1 (ADAR1), has been shown to play important roles in TNBC tumorigenesis. We posit that ADAR1 functions as a homeostatic factor protecting from internal external pressure, including metabolic stress. tested the hypothesis iron-dependent cell death pathway, ferroptosis,...
The tumor suppressors p53 and ARF collaborate to prevent unwarranted cell proliferation as such are two of the most frequently mutated genes in human cancer. Concomitant loss functional leads massive gains transformation is often observed some aggressive cancer subtypes. These phenotypic preceded by increased type I interferon (IFN) signaling that involves canonical STAT1 activation a subsequent IFN-stimulated gene (ISG) signature. Here, we show cells lacking require active JAK1...
The nucleolus is the center of ribosome synthesis, with nucleophosmin (NPM) and p19ARF proteins antagonizing one another to either promote or inhibit growth. However, basal NPM ARF form nucleolar complexes whose functions remain unknown. Nucleoli from Arf−/− cells displayed increased area, suggesting that might regulate key functions. Concordantly, biogenesis protein synthesis were dramatically elevated in absence Arf, causing these exhibit tremendous gains amounts increases cell volume....
Abstract Nucleophosmin (B23) is a nucleolar phosphoprotein that has been implicated in numerous cellular processes. In particular, nucleophosmin interacts with components of newly synthesized ribosomes to promote ribosome nuclear export. classic mitogen-induced protein, changes its expression correlating growth factor stimulation. this study, we examined the underlying mechanism induction and showed hyperproliferative signals emanating from oncogenic H-RasV12 cause tremendous increases...
Abstract In this study the regulation of macrophage expression cyclooxygenase-2 (COX-2) in response to dsRNA and virus infection was examined. Treatment RAW 264.7 macrophages with results COX-2 mRNA accumulation protein production PGE2. Similar dsRNA, encephalomyocarditis (EMCV) cells stimulates PGE2 accumulation. The dsRNA-dependent kinase (PKR), which has been shown participate gene infection, does not appear by macrophages. Expression dominant negative mutants PKR fails attenuate dsRNA-...
The double-stranded (ds) RNA-dependent protein kinase (PKR) is a primary regulator of antiviral responses; however, the ability dsRNA to activate nuclear factor-κB (NF-κB) and + interferon γ (IFN-γ) stimulate inducible nitric-oxide synthase (iNOS) expression by macrophages isolated from PKR−/− mice suggests that signaling pathways in addition PKR participate activities. We have identified novel phospholipid-signaling cascade mediates macrophage activation viral infection. Bromoenol lactone...