A5080065181- RNA modifications and cancer
- Cancer, Hypoxia, and Metabolism
- RNA Research and Splicing
- Cancer-related Molecular Pathways
- Solar and Space Plasma Dynamics
- Astro and Planetary Science
- Hemoglobinopathies and Related Disorders
- Microtubule and mitosis dynamics
- RNA regulation and disease
- Multiple Myeloma Research and Treatments
- High Altitude and Hypoxia
- RNA and protein synthesis mechanisms
- Endoplasmic Reticulum Stress and Disease
- Stellar, planetary, and galactic studies
- Autophagy in Disease and Therapy
- Cardiovascular and Diving-Related Complications
- Synthesis and Biological Evaluation
- Cancer therapeutics and mechanisms
- Protein Degradation and Inhibitors
- Diet and metabolism studies
- Neuroblastoma Research and Treatments
- Metabolism, Diabetes, and Cancer
- Heparin-Induced Thrombocytopenia and Thrombosis
- Pancreatic function and diabetes
- Chronic Myeloid Leukemia Treatments
New York University
2008-2024
Louisiana State University Health Sciences Center Shreveport
2012-2015
NYU Langone Health
2012-2015
Cornell University
2014
Howard Hughes Medical Institute
2013
Johns Hopkins University
2002-2013
University of Zurich
2011
University of Oxford
2011
Swiss Integrative Center for Human Health
2011
Texas Oncology
2009
Nonsense-mediated RNA decay (NMD) rapidly degrades both mutated mRNAs and nonmutated cellular in what is thought to be a constitutive fashion. Here we demonstrate that NMD inhibited hypoxic cells this inhibition dependent on phosphorylation of the alpha subunit eukaryotic initiation factor 2 (eIF2alpha). eIF2alpha known promote translational transcriptional up-regulation genes important for response stress. We show several these stress-induced are targets repression stabilizes mRNAs, thus...
One hundred ninety-two patients with previously untreated metastatic cancer (102 non-small-cell lung [NSCLC]; 90 colorectal cancer) were randomized to receive either ad lib nutritional intake (control group) or specific intervention during a 12-week study period when chemotherapy was administered. Those interventions counselled take oral nutrients caloric equal 1.7 1.95 times their basal energy expenditure, depending on pretreatment status ("standard" group). An augmented group have...
Human atherosclerotic plaques contain large numbers of cells deprived O(2). In murine atherosclerosis, because the are small, it is controversial whether hypoxia can occur.To examine if hypoxic cells, and regulates changes in cellular lipid metabolism gene expression macrophages.Aortic from apolipoprotein-E-deficient mice were immunopositive for hypoxia-inducible transcription factor (HIF-1α) some its downstream targets. Murine J774 macrophages rendered demonstrated significant increases...
While nonsense-mediated RNA decay (NMD) is an established mechanism to rapidly degrade select transcripts, the physiological regulation and biological significance of NMD are not well characterized. We previously demonstrated that inhibited in hypoxic cells. Here we show phosphorylation α subunit eukaryotic initiation factor 2 (eIF2α) translation by a variety cellular stresses leads inhibition eIF2α occur tumors. To explore this regulation, used unbiased approach identify approximately 750...
Abstract Many of the gene mutations found in genetic disorders, including cancer, result premature termination codons (PTC) and rapid degradation their mRNAs by nonsense-mediated RNA decay (NMD). We used virtual library screening, targeting a pocket SMG7 protein, key component NMD mechanism, to identify compounds that disrupt SMG7–UPF1 complex inhibit NMD. Several these upregulated NMD-targeted at nanomolar concentrations, with minimal toxicity cell-based assays. As expected, pharmacologic...
Abstract Hypoxia-inducible factor-1α (HIF-1α) is a transcription factor that directly transactivates genes important for the growth and metabolism of solid tumors. HIF-1α overexpressed in cancer, its level expression correlated with patient mortality. Increased synthesis or stability can be induced by hypoxia-dependent hypoxia-independent factors. Thus, expressed both nonhypoxic hypoxic cancer cells. The role nonhypoxia-mediated cell proliferation remains speculative. We have disrupted...
Preclinical and clinical studies demonstrate the feasibility of treating β-thalassemia Sickle Cell Disease (SCD) by lentiviral-mediated transfer human β-globin gene. However, previous have not addressed whether ability lentiviral vectors to increase hemoglobin synthesis might vary in different patients.We generated carrying gene with without an ankyrin insulator compared their induce vitro thalassemic mice. We found that insertion leads higher, potentially therapeutic levels through a novel...
Amino acid deprivation promotes the inhibition of kinase complex mTORC1 (mammalian target rapamycin 1) and activation GCN2 (general control nonrepressed 2). Signaling pathways downstream both kinases have been thought to independently induce autophagy. We showed that these two amino acid-sensing systems are linked. pharmacological led phosphorylation eukaryotic initiation factor 2α (eIF2α) in a mechanism dependent on catalytic subunit protein phosphatase 6 (PP6C). Autophagy induced by...
Nonsense-mediated RNA decay (NMD) is an mRNA surveillance mechanism which rapidly degrades select cytoplasmic mRNAs.We and others have shown that NMD a dynamically regulated process inhibited by amino acid deprivation, hypoxia, other cellular stresses commonly generated the tumor microenvironment.This inhibition of can result in accumulation misfolded, mutated, aggregated proteins, but how cells adapt to these aberrant proteins unknown.Here we demonstrate activates autophagy, established...
The EUV Imaging Telescope (EIT), Large Angle Spectrometric Coronagraph (LASCO), and Ultraviolet Spectrometer (UVCS) instruments aboard the SOHO satellite observed a prominence eruption (coronal mass ejection) on 1997 December 12. Ejected plasma moved at about 130 km s-1 in plane of sky showed Doppler shifts between -350 +30 s-1. appeared as strongly curved arch EIT images low corona. Emission ions ranging from Si III to O VI UVCS spectra indicates temperature range 104.5 105.5 K. morphology...
Two related ER oxidation 1 (ERO1) proteins, ERO1α and ERO1β, dynamically regulate the redox environment in mammalian endoplasmic reticulum (ER). Redox changes cysteine residues on intralumenal loops of calcium release reuptake channels have been implicated altered reuptake. These findings led us to hypothesize that ERO1 activity may affect cardiac functions are dependent intracellular flux. We established mouse lines with loss function insertion mutations Ero1l Ero1lb encoding ERO1β. The...
The Myc transcription factor plays a vital role in both normal cellular physiology and many human cancers. We have recently demonstrated that nonsense-mediated RNA decay (NMD), mechanism rapidly degrades select mRNAs, is inhibited by the stress-induced phosphorylation of translation initiation eIF2α, this inhibition stabilizes transcripts necessary for tumorigenesis. Here, we demonstrate NMD high expression. show likely due to ability generate reactive oxygen species augment endoplasmic...
The hostile tumor microenvironment results in the generation of intracellular stresses including hypoxia and nutrient deprivation. In order to adapt such conditions, cell utilizes several stress-response mechanisms, attenuation protein synthesis, inhibition cellular proliferation, induction autophagy. Autophagy leads degradation contents, damaged organelles mutant proteins, which can then use as an alternate energy source. Two integral changes signaling milieu promote a response include...
Thirty-seven healthy untrained males (age=21 ± 1 yr; range=19 to 35 yr) were studied determine the effects of 10 wk lowand high-repetition resistive training on lipoprotein-lipid profiles. Subjects assigned 3 groups: a low-repetition group (TV=15) that trained using 4 6 repetitions maximum or (N=14) used 14 16 in their an inactive control (N=8). The number sets was adjusted equalize workloads. Muscular strength increased significantly both groups as indicated by increase one-repetition test...
Recent whole genome melanoma sequencing studies have identified recurrent mutations in the gene encoding catalytic subunit of serine/threonine phosphatase 6 (PPP6C/PP6C). However, biochemical, functional, and clinical ramifications these are unknown. Sequencing PP6C from patients with (233 primary 77 metastatic specimens) extended prospective outcome revealed a large number hotspot both melanoma. Despite minimal association between stage presence melanoma, subpopulation cells within each...
It has been suggested that regulation of glucose-6-phosphatase by insulin plays a role in the suppression hepatic glucose production during feeding. We used (measured with D-[3-3H]glucose infusion method) as an indicator substrate flux through vivo. Compared saline controls, (7 mU · min−1 kg−1, euglycemic clamp) suppressed virtually completely both fasted (32.4 ± 2.4 vs. –6.1 14 μmol kg−1) and fed (64.6 6.4 5.5 5.2 rats. Whereas was totally suppressed, [glucose-6-phosphate] liver cytosol...
Abstract T cell anergy has been demonstrated to play a role in maintaining peripheral tolerance self Ags as well means by which tumors can evade immune destruction. Although the precise pathways involved induction have yet be elucidated, it linked TCR engagement setting of cycle arrest. Indeed, rapamycin, inhibits proliferation G1, ability promote even presence costimulation. To better define regulating induction, we used novel cyclophilin-binding ligand, sanglifehrin A (SFA). We demonstrate...
Summary The clinical relevance of heparin-induced antibodies (HIA) in the absence thrombocytopenia remains to be defined. aims this study were (i) determine prevalence HIA patients treated by dialysis, (ii) and (HIT), (iii) test whether are associated with adverse outcomes. Sera from 740 hemodialysis (HD, n=596) peritoneal dialysis (PD, n=144) tested for (IgG, IgA or IgM) masked investigators at approximately six months after enrolment Choices Healthy Outcomes Caring End-Stage Renal Disease...