A5025205189- Hemoglobinopathies and Related Disorders
- HIV Research and Treatment
- Iron Metabolism and Disorders
- RNA modifications and cancer
- HIV/AIDS drug development and treatment
- RNA Research and Splicing
- Erythrocyte Function and Pathophysiology
- Viral Infections and Outbreaks Research
- Epigenetics and DNA Methylation
- Genetic Associations and Epidemiology
- Blood groups and transfusion
- Viral Infections and Vectors
- RNA Interference and Gene Delivery
- Folate and B Vitamins Research
- Trace Elements in Health
- HIV-related health complications and treatments
- RNA and protein synthesis mechanisms
- Cancer, Hypoxia, and Metabolism
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Immune Cell Function and Interaction
- Hepatitis B Virus Studies
- Genomics and Chromatin Dynamics
- Telomeres, Telomerase, and Senescence
- Genomics and Rare Diseases
- Cancer-related molecular mechanisms research
Howard University
2016-2025
Georgetown University Medical Center
2021
Georgetown University
2021
Chuvash State University
2014-2020
University of Illinois Chicago
2014
Boston University
2014
National Heart Lung and Blood Institute
2014
National Institutes of Health
2014
University Medical Center Utrecht
2014
University of Pittsburgh
2014
Patients with sickle cell disease (SCD) have markers of chronic inflammation, but the mechanism inflammation and its relevance to patient survival are unknown.
The filovirus Ebola (EBOV) causes the most severe hemorrhagic fever known. EBOV RNA-dependent polymerase complex includes a filovirus-specific VP30, which is critical for transcriptional but not replication activity of polymerase; to support transcription, VP30 must be in dephosphorylated form. Here we show that phosphorylated only at N-terminal serine clusters identified previously also threonine residues positions 143 and 146. We host cell protein phosphatase 1 (PP1) controls...
Ebola virus (EBOV) is an enveloped, ssRNA from the family Filoviridae capable of causing severe hemorrhagic fever with up to 80-90% mortality rates. The most recent outbreak EBOV in West Africa starting 2014 resulted over 11,300 deaths; however, long-lasting persistence and recurrence survivors has been documented, potentially leading further transmission virus. We have previously shown that exosomes cells infected HIV-1, HTLV-1 Rift Valley Fever are able transfer viral proteins non-coding...
Respiratory syncytial virus (RSV) RNA synthesis occurs in cytoplasmic inclusion bodies (IBs) which all the components of viral polymerase are concentrated. In this work, we show that RSV P protein recruits essential transcription factor M2-1 to IBs independently phosphorylation state M2-1. We also dephosphorylation is achieved by a complex formed between and cellular phosphatase PP1. identified PP1 binding site P, an RVxF-like motif located nearby upstream region. NMR confirmed both P-M2-1...
Abstract: Despite the remarkable success of combination antiretroviral therapy at curtailing HIV progression, emergence drug-resistant viruses, chronic low-grade inflammation, and adverse effects treatments, including metabolic disorders collectively present impetus for development newer safer drugs. Curcumin, a phytochemical compound, was previously reported to have some in vitro anti-HIV anti-inflammatory activities, but poor bioavailability has limited its clinical utility. To circumvent...
Sickle cell disease (SCD) is an inherited hemoglobin disorder marked by red blood sickling, resulting in severe anemia, painful episodes, extensive organ damage, and shortened life expectancy. In SCD, increased iron levels can trigger ferroptosis, a specific type of death characterized reactive oxygen species (ROS) lipid peroxide accumulation, leading to damage impairments. The intricate interplay between iron, inflammation, oxidative stress SCD underscores the necessity thoroughly...
Abstract Background Transcription of HIV-1 genes is activated by Tat protein, which induces phosphorylation RNA polymerase II (RNAPII) C-terminal domain (CTD) CDK9/cyclin T1. Earlier we showed that CDK2/cyclin E phosphorylates in vitro . We also CDK2 transcription and inhibition expression interference inhibits viral replication cultured cells. In the present study, analyzed whether phosphorylated cells has a regulatory effect on transcription. Results identified Ser 16 46 residues as...
Abstract Background Upon HIV entry into target cells, viral cores are released and rearranged reverse transcription complexes (RTCs), which support also protect transport cDNA to the site of integration. RTCs composed cellular proteins that originate from both producer latter entering cell within core. However, proteome HIV-1 in context type cells has not yet been characterized. Results We examined proteomic profiles purified NL4-3 virions assembled Sup-T1 (T lymphocytes), PMA vitamin D 3...
Background. The mechanisms of severe malarial anemia and cerebral malaria, which are extreme manifestations Plasmodium falciparum not fully understood. Methods. Children aged <6 years from southern Zambia presenting to the hospital with (n = 72), malaria 28), or uncomplicated 66) were studied prospectively. overlapping excluded. Results. Low interleukin 10 concentrations had strongest association (standard β .61; P < .001) followed by high tumor necrosis factor α sFas concentrations, low...
HIV-1 transcription is activated by Tat protein, which recruits cyclin-dependent kinase 9 (CDK9)/cyclin T1 and other host transcriptional coactivators to the <i>HIV-1</i> promoter. itself phosphorylated CDK2, inhibition of CDK2 small interfering RNA, iron chelator 2-hydroxy-1-naphthylaldehyde isonicotinoyl hydrazone (<i>311</i>), deferasirox (ICL670) inhibits transcription. Here we have analyzed a group novel di-2-pyridylketone thiosemicarbazone- 2-benzoylpyridine thiosemicarbazone-based...
Human immunodeficiency virus, type 1 (HIV-1), Tat protein activates viral gene expression through promoting transcriptional elongation by RNA polymerase II (RNAPII). In this process enhances phosphorylation of the C-terminal domain (CTD) RNAPII activating cell cycle-dependent kinases (CDKs) associated with general transcription factors promoter complex, specifically CDK7 and CDK9. We reported a Tat-associated T-cell-derived kinase, which contained CDK2. Here, we provide further evidence that...
Abstract Background Physiological regulation of cellular iron involves export by the membrane protein, ferroportin, expression which is induced and negatively modulated hepcidin. We previously showed that chelation associated with decreased HIV-1 transcription. hypothesized increased ferroportin might be transcription, degradation hepcidin in turn induce transcription replication. Here, we analyzed effect on Results Expression was reduced 293T cells addition to ferroportin-expressing...
HIV-1 transcription is activated by the viral Tat protein that recruits host positive elongation factor-b (P-TEFb) containing CDK9/cyclin T1 to promoter. P-TEFb in cells exists as a lower molecular weight dimer and high complex of 7SK RNA, T1, HEXIM1 several additional proteins. Our previous studies implicated CDK2 regulation. We also found inhibition iron chelators leads CDK9 activity, suggesting functional link between CDK9. Here, we investigate whether phosphorylates regulates its...
Objective Some studies suggest that HIV infection progresses slowly in patients with sickle cell disease (SCD). The authors aimed to determine the relationships between SCD and infection. Methods National Hospital Discharge Survey data from adult African–Americans period of 1997–2009 were analysed. comorbidities infections hospital discharges Multiple logistic regression was used test association HIV. For comparative purposes, hepatitis B virus (HBV) C (HCV) also assessed. Results 423 431...
Ebola virus (EBOV) infections are characterized by a pronounced lymphopenia that is highly correlative with fatalities. However, the mechanisms leading to T-cell depletion remain largely unknown. Here, we demonstrate both viral mRNAs and antigens detectable in CD4+ T cells despite absence of productive infection. A protein phosphatase 1 inhibitor, 1E7-03, siRNA-mediated suppression were used de novo synthesis RNAs cells, respectively. Cell-to-cell fusion permissive Huh7 non-permissive Jurkat...
Background Sickle Cell Disease (SCD) is an inherited blood disorder that leads to hemolytic anemia, pain, organ damage and early mortality. It characterized by polymerized deoxygenated hemoglobin, rigid sickle red cells vaso-occlusive crises (VOC). Recurrent hypoxia-reperfusion injury in the gut of SCD patients could increase tissue injury, permeability, bacterial translocation. In this context, microbiome, a major player health disease, might have significant impact. This study sought...
Transcription by RNA polymerase-II (RNAPII) is controlled multisite phosphorylation of the heptapeptide repeats in C-terminal domain (CTD) largest subunit. Phosphorylation CTD mediated cyclin-dependent protein kinases Cdk7 and Cdk9, whereas serine/threonine phosphatase FCP1 dephosphorylates CTD. We have recently reported that human immunodeficiency virus-1 (HIV-1) transcription positively regulated phosphatase-1 (PP1) PP1 recombinant Here, we provide further evidence can dephosphorylate...
Transcription of human immunodeficiency virus (HIV)-1 genes is activated by HIV-1 Tat protein, which induces phosphorylation the C-terminal domain RNA polymerase-II CDK9/cyclin T1. We previously showed that Tat-induced transcription regulated protein phosphatase-1 (PP1). In present study we demonstrate interacts with PP1 and disruption this interaction prevents induction transcription. show in part through binding Val36 Phe38 to involved nuclear subnuclear targeting PP1. The mutant...
Profiling integral plasma membrane proteins is of particular importance for the identification new biomarkers diagnosis and drug development. We report in this study surface markers by performing comparative proteomics established human immunodeficiency virus-1 (HIV-1) latent cell models parental lines. To end we isolated using a biotin-directed affinity purification method. Isolated were separated two-dimensional gel electrophoresis identified matrix-assisted laser...
ABSTRACT The human immunodeficiency virus type 1 (HIV-1) Tat is a 14-kDa viral protein that acts as potent transactivator by binding to the transactivation-responsive region, structured RNA element located at 5′ end of all HIV-1 transcripts. transactivates gene expression inducing phosphorylation C-terminal domain polymerase II through several Tat-activated kinases and recruiting chromatin-remodeling complexes histone-modifying enzymes long terminal repeat. Histone acetyltransferases,...