Marina Jerebtsova

Marina Jerebtsova
Howard University | HU · Department of Microbiology

PhD

About

74
Publications
5,243
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1,054
Citations
Additional affiliations
March 1999 - June 2014
Children's National Medical Center
Position
  • Research Assistant

Publications

Publications (74)
Article
Background: Sickle cell nephropathy (SCN) is one of the most common complications of SCD, leading in most cases to chronic kidney disease (CKD) and end-stage renal disease (ESRD). Despite the high prevalence of CKD in sickle cell disease (SCD) patients, there remains a poor understanding of the pathophysiological mechanism of SCN and a lack of biom...
Article
BACKGROUND : Autophagy plays an important role in multiple cell processes including elimination of misfolded proteins and damaged organelles, clearance of intracellular microbes and regulation of innate immunity. Autophagic activity is significantly up regulated in diseases characterized by proteins aggregation such as Alzheimer's, Huntington's, an...
Article
Introduction Patients with Sickle cell disease (SCD) have lower risk for HIV-1 infection. We showed that ex vivo HIV-1 replication is blocked in SCD PBMCs in part because of the increased expression of ferroportin (FPN) and activation of SAMHD1, a host antiviral restriction factor. We hypothesized that rupture of sickling red blood cells releases s...
Article
Introduction: Chronic kidney disease (CKD) is a prevalent complication of sickle cell anemia (SCA). Hyperfiltration that delayed detection of CKD is common in SCA patients. Identification of novel urinary biomarkers correlating with glomerular filtration rates may help to detect and predict progression of renal disease. Methods: Reanalysis of ma...
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Over 80% of all children living with HIV reside in Africa and are at risk of developing HIV-associated nephropathy (HIVAN). Once HIVAN is established in children, it is difficult to revert its progression to chronic kidney failure even using antiretroviral drugs. Therefore, new therapeutic strategies are needed. Previous studies showed that the ris...
Article
BACKGROUND : Sickle cell anemia (SCA) patients are predisposed to the development of chronic kidney disease (CKD). Vascular dysfunction plays an important role in the etiology of CKD and is a major complication in SCA. Biomarkers of endothelial dysfunction VCAM and Activin A were recently described for diagnostics of CKD in Diabetic Kidney Disease...
Article
BACKGROUND : More than 60% of sickle cell anemia (SCA) adults develop chronic kidney disease (CKD). Identification of early stages of CKD in SCA patients at high risk of complications could lead to personalized treatment and better prognosis. Recently we identified several urinary biomarkers that can differentiate CKD stage 1 in SCA patients. These...
Article
Concerted action of numerous positively acting cellular factors is essential for Human immunodeficiency virus type 1 (HIV-1) replication but in turn is challenged by anti-viral restriction factors. Previously we showed that ex vivo one round HIV-1 replication and replication of fully competent T-tropic HIV-1(IIIB) is significantly reduced in periph...
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While antiretroviral therapy increases the longevity of people living with HIV (PLWH), about 30% of this population suffers from three or more concurrent comorbidities, whose mechanisms are not well understood. Chronic activation and dysfunction of the immune system could be one potential cause of these comorbidities. We recently demonstrated reduc...
Article
BACKGROUND : Sickle cell anemia (SCA) is a chronic hemolytic disease that is characterized by chronic presence of low-level plasma hemoglobin (Hb, 3-10 µM). Plasma Hb can reduce NO availability, induce endothelium damage and activate coagulation cascade and inflammation leading to development of vasculopathies. The Hb scavenging proteins, haptoglob...
Article
BACKGROUND: Chronic kidney disease (CDK) is a serious and highly prevalent complication of Sickle cell anemia (SCA). Proteinuria and microalbuminuria can be under-detected in SCA because of the renal concentrating defect. Hence, complementary diagnostic biomarkers are necessary for early detection of CKD in patient with SCA. Our recent study identi...
Article
Background: Ebola virus (EBOV) infection causes severe hemorrhagic fever. EBOV transcription is controlled by host protein phosphatase 1 (PP1), which dephosphorylates VP30 protein. We previously developed 1E7-03, a compound targeting a noncatalytic site of PP1 that induced VP30 phosphorylation and inhibited EBOV transcription. Here, we attempted t...
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Sickle cell disease patients are at increased risk of developing a chronic kidney disease. Endothelial dysfunction and inflammation associated with hemolysis lead to vasculopathy and contribute to the development of renal disease. Here we used a Townes sickle cell disease mouse model to examine renal endothelial injury. Renal disease in Townes mice...
Article
BACKGROUND: Chronic kidney disease (CKD) is common in patients with sickle cell disease (SCD). However, the progression of CKD in SCD and factors associated with such progression remain poorly defined. Liquid chromatography mass spectrometry (LC-MS) based quantitative proteomics has become a highly potent method for biomarker discovery due to growi...
Article
BACKGROUND: Patients with Sickle Cell Disease (SCD) have an approximately three-fold higher risk of developing chronic kidney disease (CKD) than the general population. Endothelial dysfunction and inflammation which are induced by hemolysis and lead to vasculopathy are major mechanisms in the development of CKD. Red blood cells (RBCs) hemolysis ins...
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We recently identified the protein phosphatase-1 - targeting compound, 1E7-03 which inhibited HIV-1 in vitro. Here, we investigated the effect of 1E7-03 on HIV-1 infection in vivo by analyzing its metabolic stability and antiviral activity of 1E7-03 and its metabolites in HIV-1 infected NSG-humanized mice. 1E7-03 was degraded in serum and formed tw...
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Key Points Ferroportin reduces intracellular iron, inhibits CDK2 and suppresses SAMHD1 phosphorylation thus inhibiting HIV-1 RT. Ferroportin expression leads to overexpression of IKBα and inhibition of HIV-1 transcription.
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Protein phosphatase 1 (PP1), a cellular serine/threonine phosphatase, is targeted to cellular promoters by its major regulatory subunits, PP1 nuclear targeting subunit, nuclear inhibitor of PP1 (NIPP1) and RepoMan. PP1 is also targeted to RNA polymerase II (RNAPII) by NIPP1 where it can dephosphorylate RNAPII and cycle-dependent kinase 9 (CDK9). He...
Article
BACKGROUND: Chronic kidney disease (CKD) is a prevalent complication of sickle cell disease (SCD) and associated with early mortality. Hemoglobinuria is a risk factor for the development and progression of CKD. Discovery and validation of non-invasive biomarkers for early stage renal disease are needed to facilitate optimal CKD treatment. Mass-spec...
Article
Background: Chronic kidney disease (CKD) is a prevalent complication of sickle cell disease (SCD) associated with early mortality. Hemoglobinuria is a risk factor for the development of albuminuria and CKD. Currently, there are no biomarkers that predict outcome of CKD. Mass-spectrometry analysis of patient urine is a highly potent modern method fo...
Article
BACKGROUND: Hemolysis and frequent blood transfusions lead to the iron overload and organ iron accumulation in patients with red blood cells disorders. The pattern of iron accumulation within different organs is disease specific. Abnormalities of renal iron metabolism and cortical iron deposition is characteristic for sickle cell disease (SCD) but...
Article
Background More than 50% patients with sickle cell disease (SCD) develop renal glomerular disease. Its pathophysiology is likely to be multifactorial, being affected by hyperfiltration, glomerular hypertension, ischemia-reperfusion injury, oxidative stress, and endothelial dysfunction. Ischemia-reperfusion is associated with significant recruitment...
Article
Background Urinary hepcidin is a potential biomarker of renal inflammation and acute kidney injury (AKI) which is elevated in sickle cell disease (SCD). Hepcidin in circulation is filtered through glomeruli filtration barrier and reabsorbed by the renal tubules. Hepcidin can also be synthesized by the kidney tubular cells. Thus, increased urinary l...
Article
Critically ill children can develop bleeding complications when treated with heparin-like drugs. These events are usually attributed to the anti-coagulant activity of these drugs. However, previous studies showed that Fibroblast Growth Factor-2 (FGF-2), a heparin binding growth factor released in the circulation of these patients, could precipitate...
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Complete eradication of HIV-1 infection is impeded by the existence of latent HIV-1 reservoirs in which the integrated HIV-1 provirus is transcriptionally inactive. Activation of HIV-1 transcription requires the viral Tat protein and host cell factors, including protein phosphatase-1 (PP1). We previously developed a library of small compounds that...
Article
The current Ebola virus disease (EVD) outbreak in West Africa is the largest with over 5100 deaths in four West African countries as of 14 November 2014. EVD has high case-fatality rates but no licensed treatment or vaccine is yet available. Several vaccine candidates that protected nonhuman primates are not yet available for clinical use. Slow dev...
Article
The effectiveness of treatment of renal diseases is limited because the lack of diagnostic, prognostic and therapeutic markers. Despite the more than a decade of intensive investigation of urinary biomarkers, no new clinical biomarkers were approved. This is in part because the early expectations toward proteomics in biomarkers discovery were signi...
Article
Background and purpose: HIV-1 transcription is activated by the Tat protein which recruits the cyclin-dependent kinase CDK9/cyclin T1 to TAR RNA. Tat binds to protein phosphatase-1 (PP1) through the Q(35) VCF(38) sequence and translocates PP1 to the nucleus. PP1 dephosphorylates CDK9 and activates HIV-1 transcription. We have synthesized a low MW...
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Podocyte injury has a critical role in the pathogenesis of HIV-associated nephropathy (HIVAN). The HIV-1 transactivator of transcription (Tat), combined with fibroblast growth factor-2 (FGF-2), can induce the dedifferentiation and proliferation of cultured human podocytes. Cellular internalization of Tat requires interactions with heparan sulfate p...
Article
5187 Renal glomerular endothelial cells are specialized cells with an important role in physiological filtration and glomerular disease. However, maintenance of human primary endothelial cells requires stimulation with serum and growth factors that often results in modification of the cells properties. Previously, expression of early adenovirus reg...
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Summary Renal glomerular endothelial cells are specialized cells with an important role in physiological filtration and glomerular disease. However, maintenance of human primary endothelial cells requires stimulation with serum and growth factors that often results in modification of the cells properties. Previously, expression of early adenovirus...
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A major challenge in studies of human diseases involving macrophages is low yield and heterogeneity of the primary cells and limited ability of these cells for transfections and genetic manipulations. To address this issue, we developed a simple and efficient three steps method for somatic 293T cells reprogramming into monocytes and macrophage-like...
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Fibroblast growth factor-2 (FGF-2) is an angiogenic growth factor involved in renal growth and regeneration. Previous studies in rodents revealed that single intrarenal injections of FGF-2 improved the outcome of acute kidney injury (AKI). Septic children usually show elevated plasma levels of FGF-2, and are at risk of developing AKI. However, the...
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CDK9/cyclin T1, a key enzyme in HIV-1 transcription, is negatively regulated by 7SK RNA and the HEXIM1 protein. Dephosphorylation of CDK9 on Thr186 by protein phosphatase 1 (PP1) in stress-induced cells or by protein phosphatase M1A in normally growing cells activates CDK9. Our previous studies showed that HIV-1 Tat protein binds to PP1 through the...
Article
CDK9/cyclin T1, a key enzyme in HIV-1 transcription, is negatively regulated by 7SK RNA and the HEXIM1 protein. Dephosphorylation of CDK9 on Thr186 by protein phosphatase-1 (PP1) in stress-induced cells or by protein phosphatase M1A in normally growing cells activates CDK9. Our previous studies showed that HIV-1 Tat protein binds to protein phospha...
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Transcription of eukaryotic genes is regulated by phosphorylation of serine residues of heptapeptide repeats of the carboxy-terminal domain (CTD) of RNA polymerase II (RNAPII). We previously reported that protein phosphatase-1 (PP1) dephosphorylates RNAPII CTD in vitro and inhibition of nuclear PP1-blocked viral transcription. In this article, we a...
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HIV-1 transcription is activated by HIV-1 Tat protein, which recruits cyclin-dependent kinase 9 (CDK9)/cyclin T1 and other host transcriptional coactivators to the HIV-1 promoter. Tat itself is phosphorylated by CDK2, and inhibition of CDK2 by small interfering RNA, the iron chelator 2-hydroxy-1-naphthylaldehyde isonicotinoyl hydrazone (311), and t...
Article
HIV transcription is induced by the HIV-1 Tat protein, in concert with cellular co-factors including CDK9, CDK2, NF-kappaB, and others. The cells of most of the body's organs are exposed to approximately 3-6% oxygen, but most in vitro studies of HIV replication are conducted at 21% oxygen. We hypothesized that activities of host cell factors involv...
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Previous studies using different techniques have shown that adenoviral-mediated gene transfer to different tissues, including the kidney, is more efficient in neonatal mice. In this study, we report a simple technique that allows an efficient and long term expression of beta-galactosidase (beta-gal) in the heart of newborn mice. Newborn and adult C...
Article
HIV-1 progression may be faster and survival shorter in HIV-positive patients with higher iron stores. Some studies indicate that iron stimulates HIV-1 viral replication and iron chelation decreases viral replication in cultured cells. Iron depletion may remove iron from prolyl hydroxylases and increases HIF-1a protein level thus mimicking hypoxia....
Article
HIV-1 replication is induced by the excess of iron and iron chelation by desferrioxamine (DFO) inhibits viral replication in HIV-1 infected CEM T cells [1]. Treatment of cells with DFO or 2-hydroxy-1-naphthylaldehyde isonicotinoyl hydrazone inhibits expression of proteins that regulate cell-cycle progression, including cycle-dependent kinase 2 (CDK...
Article
HIV-1 replication is induced by an excess of iron and iron chelation by desferrioxamine (DFO) inhibits viral replication by reducing proliferation of infected cells. Treatment of cells with DFO and 2-hydroxy-1-naphthylaldehyde isonicotinoyl hydrazone (311) inhibit expression of proteins that regulate cell-cycle progression, including cycle-dependen...
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Human immunodeficiency virus (HIV) and hepatitis C virus (HCV) pose major public health concerns worldwide. HCV is clearly associated with the occurrence of hepatocellular carcinoma, and recently HIV infection has also been linked to the development of a multitude of cancers. Previously, we identified a novel nucleoside analog transcriptional inhib...
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Pentosan polysulfate (PPS) is a heparin-like polysaccharide that can affect the binding interactions of fibroblast growth factor (FGF-2) with its high-affinity receptors. Patients with angiogenic tumors frequently show high levels of FGF-2 in the circulation. Since FGF-2 is a heparin-binding angiogenic growth factor, PPS has been used successfully...
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The emergence of drug-resistant HIV-1 strains presents a challenge for the design of new drugs. Targeting host cell factors involved in the regulation of HIV-1 replication might be one way to overcome the resistance of HIV-1 to anti-viral agents. Our recent studies identified protein phosphatase-1 (PP1) as an important regulator of HIV-1 transcript...
Article
Iron chelation leads to reduced cell cycle-dependent kinase 2 (CDK2) activity (reviewed in Biochim Biophys Acta2002;1603:31–46). Elongation of HIV-1 transcription is mediated by the interaction of HIV Tat with host cell cycle-dependent kinase 9 (CDK9)/cyclin T1, which phosphorylates the C-terminal domain of RNA polymerase II, and our recent studies...
Article
The hypoxic response is an important component of the body’s reaction to impaired tissue oxygenation associated with the anemia and vasoocclusive episodes of sickle cell disease (SCD). It has been reported that HIV infection progresses relatively slowly in patients with SCD (Am J Hematol1998;59:199–207). HIV-1 Tat protein promotes transcription of...
Data
Full-text available
Purification of CDK2/cyclin E. Mixed mono Q fractions of CDK2 and cyclin E (Mono Q lane) were purified on Superdex column. Fractions 37, 39, 41, 43, and 45 were analyzed for the presence of CDK2 and cyclin E by Coumassie staining.
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Basic fibroblast growth factor (bFGF) is a heparin-binding growth factor that is accumulated in human dysplastic and cystic renal diseases. Previous studies have shown that bFGF can modulate the growth of developing renal tubules; however, its role in the pathogenesis of renal cyst formation is not clearly understood. Here, we tested the hypothesis...
Article
RNA interference (RNAi) is a process in which double-stranded RNA triggers the silencing of gene expression in a sequence-specific manner. In mammalian cells, approximately 21-nucleotide small interfering RNA duplexes guide cognate mRNA degradation in a sequence-specific manner by RNA-induced silencing complex. RNAi was successfully applied to inhi...
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Transcription of HIV-1 genes is activated by HIV-1 Tat protein, which induces phosphorylation of RNA polymerase II (RNAPII) C-terminal domain (CTD) by CDK9/cyclin T1. Earlier we showed that CDK2/cyclin E phosphorylates HIV-1 Tat in vitro. We also showed that CDK2 induces HIV-1 transcription in vitro and that inhibition of CDK2 expression by RNA int...
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The role of circulating growth factors in the pathogenesis of childhood HIV-1-associated nephropathy (HIVAN) is not clearly understood. In previous studies, we found a significant accumulation of fibroblast growth factor-2 (FGF-2) in the circulation and kidneys of children with HIVAN. The purpose of this study was to determine whether circulating F...
Article
The systemic delivery of recombinant adenoviral (rAd) vectors to renal glomeruli has been problematic due to the rapid clearance of the circulating virus by the liver. We have previously shown that prolonged retention of rAd vectors in the circulation by liver bypass improves the transduction of renal glomerular cells in adult mice and rats. This s...
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Transcription of human immunodeficiency virus (HIV)-1 genes is activated by HIV-1 Tat protein, which induces phosphorylation of the C-terminal domain of RNA polymerase-II by CDK9/cyclin T1. We previously showed that Tat-induced HIV-1 transcription is regulated by protein phosphatase-1 (PP1). In the present study we demonstrate that Tat interacts wi...
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We recently reported that protein phosphatase 1 (PP1) dephosphorylates RNA polymerase II C-terminal repeats and regulates HIV-1 transcription in vitro. Here we provide evidence that PP1 is also required for Tat-induced HIV-1 transcription and for viral replication in cultured cells. Inhibition of PP1 by overexpression of nuclear inhibitor of PP1 (N...