A5062655427- Protein Degradation and Inhibitors
- Glioma Diagnosis and Treatment
- Migraine and Headache Studies
- Cytokine Signaling Pathways and Interactions
- DNA Repair Mechanisms
- Ubiquitin and proteasome pathways
- Epigenetics and DNA Methylation
- Oxidative Organic Chemistry Reactions
- Microtubule and mitosis dynamics
- Bioactive Compounds and Antitumor Agents
- RNA modifications and cancer
- interferon and immune responses
- Histone Deacetylase Inhibitors Research
- MicroRNA in disease regulation
- Chemical Synthesis and Reactions
- PARP inhibition in cancer therapy
- RNA Research and Splicing
- RNA and protein synthesis mechanisms
- Glycosylation and Glycoproteins Research
- Colorectal Cancer Treatments and Studies
- Genetic factors in colorectal cancer
- Carbohydrate Chemistry and Synthesis
- Cancer-related gene regulation
- Synthesis and Biological Activity
- Hedgehog Signaling Pathway Studies
University of Nebraska Medical Center
2016-2024
Nebraska Medical Center
2022-2024
University of Pittsburgh
2023
Impel Neuropharma (United States)
2019-2023
University of Engineering & Management
2016-2023
Indian Institute of Technology Kharagpur
2005-2023
Jagadguru Rambhadracharya Handicapped University
2023
Seattle University
2023
Institute of Engineering
2017-2021
University of Washington
2008-2020
Interleukin-6 (IL-6) is a well-established, independent indicator of multiple distinct types cardiovascular disease and all-cause mortality. In this review, we present current understanding the roles that IL-6 its signaling pathways through glycoprotein 130 (gp130) play in homeostasis. highly inducible vascular tissues actions angiotensin II (Ang II) peptide, where it acts paracrine manner to signal two mechanisms, first being classic membrane receptor initiated pathway second,...
Objective— Dysregulated angiotensin II (Ang II) signaling induces local vascular interleukin-6 (IL-6) secretion, producing leukocyte infiltration and life-threatening aortic dissections. Precise mechanisms by which IL-6 recruitment remain unknown. T-helper 17 lymphocytes (Th17) have been implicated in pathology, but their role the development of dissections is poorly understood. Here, we tested relationship IL-6–signal transducer activator transcription-3 with Th17-induced inflammation...
Pancreatic ductal adenocarcinoma (PDAC), one of the most aggressive types cancer, is characterized by aberrant activity oncogenic KRAS. A nuclease-hypersensitive GC-rich region in KRAS promoter can fold into a four-stranded DNA secondary structure called G-quadruplex (G4), known to regulate expression. However, factors that stable G4 formation genome and expression PDAC are largely unknown. Here, we show APE1 (apurinic/apyrimidinic endonuclease 1), multifunctional repair enzyme, G4-binding...
We describe a new congenital disorder of glycosylation, CDG-If. The patient has severe psychomotor retardation, seizures, failure to thrive, dry skin and scaling with erythroderma, impaired vision. CDG-If is caused by defect in the gene MPDU1, human homologue hamster Lec35, first affect use, rather than biosynthesis, donor substrates for lipid-linked oligosaccharides. This leads synthesis incomplete poorly transferred precursor oligosaccharides lacking both mannose glucose residues....
Diospyrin is a plant product that has significant inhibitory effect on the growth of <i>Leishmania donovani</i> promastigotes. This compound inhibits catalytic activity DNA topoisomerase I parasite. Like camptothecin, it induces mediated cleavage <i>in vitro</i>. Treatment with diospyrin before addition no effect. Preincubation in relaxation reaction increases this inhibition. Our results suggest bis-naphthoquinone exerts its by binding enzyme and stabilizing I-DNA "cleavable complex."...
A MeOH extract of Swertia chirata found to inhibit the catalytic activity topoisomerase I Leishmania donovani was subjected fractionation yield three secoiridoid glycosides: amarogentin (1), amaroswerin (2), and sweroside (3). Amarogentin is a potent inhibitor type DNA from exerts its effect by interaction with enzyme, preventing binary complex formation.
Signal transducer and activator of transcription 3 (STAT3) is a latent factor mainly activated by the interleukin-6 cytokine family. Previous studies have shown that STAT3 recruits p300, coactivator whose intrinsic histone acetyltransferase activity essential for transcription. Here we investigated function NH(2)-terminal domain how its interaction with p300 regulates signal transduction. In STAT3(-/-) mouse embryonic fibroblasts, stably expressed NH(2) terminus-deficient mutant...
Signal Transducer and Activator of Transcription 3 (STAT3) is a transcription factor that plays crucial role in interleukin-6 (IL-6) signaling, mediating the acute-phase induction human Angiotensinogen (hAGT) gene hepatocytes. We showed earlier IL-6 induces acetylation STAT3 NH 2 -terminus by recruitment p300 coactivator. had also observed physical interaction Histone Deacetylase1 (HDAC1) an IL-6-dependent manner leads to transcriptional repression. In this study, we sought elucidate...
Apurinic/apyrimidinic (AP) sites, the most frequently formed DNA lesions in genome, inhibit transcription and block replication. The primary enzyme that repairs AP sites mammalian cells is endonuclease (APE1), which functions through base excision repair (BER) pathway. Although mechanism by APE1 vitro has been extensively investigated, it largely unknown how cells. Here, we show acetylated (AcAPE1) after binding to chromatin AcAPE1 exclusively present on throughout cell cycle. Positive...
The Lec35 gene product (Lec35p) is required for utilization of the mannose donor mannose-P-dolichol (MPD) in synthesis both lipid-linked oligosaccharides (LLOs) and glycosylphosphatidylinositols, which are important functions such as protein folding membrane anchoring, respectively. hamster shown to encode previously identified cDNA SL15, corrects mutant phenotype predicts a novel endoplasmic reticulum protein. alleles Lec35.1 Lec35.2 characterized, human (mannose-P-dolichol defect 1) was...
The signal transducer and activator of transcription 3 (STAT3) is an IL-6-inducible factor that mediates the hepatic acute phase response (APR). Using gamma-fibrinogen (FBG) as a model APR, we investigated requirement complex STAT3 with cyclin-dependent kinase 9 (CDK9) on gamma-FBG expression in HepG2 hepatocarcinoma cells. IL-6 induces rapid nuclear translocation Tyr-phosphorylated forms CDK9 nondenaturing co-immunoprecipitation confocal colocalization assays. To further understand this...
CYP4Z1 is an "orphan" cytochrome P450 (P450) enzyme that has provoked interest because of its hypothesized role in breast cancer through formation the signaling molecule 20-hydroxyeicosatetraenoic acid (20-HETE). We expressed human
// Nagendra K. Chaturvedi 1 , Matthew J. Kling 2 Don W. Coulter Timothy R. McGuire 3 Sutapa Ray Varun Kesherwani 4 Shantaram S. Joshi and Graham Sharp Departments of Pediatrics, Hematology Oncology, University Nebraska Medical Center, Omaha, NE 69198, USA Genetics, Cell Biology Anatomy, Pharmacy Practice, Pathology Microbiology, Correspondence to: Chaturvedi, email: nchaturvedi@unmc.edu Keywords: medulloblastoma; hedgehog/PI3K-mTOR pathway; MYC; small molecule inhibitors; chemotherapy...
Apurinic/apyrimidinic (AP) sites are frequently generated in the genome by spontaneous depurination/depyrimidination or after removal of oxidized/modified bases DNA glycosylases during base excision repair (BER) pathway. Unrepaired AP mutagenic and block replication transcription. The primary enzyme to mammalian cells is endonuclease (APE1), which plays a key role this Although overexpression APE1 diverse cancer types its association with chemotherapeutic resistance well documented,...
Angiotensin II, a potent vasoactive peptide produced by proteolysis of the angiotensinogen (AGT) prohormone, plays critical role in cardiovascular homeostasis. Recently we showed that IL-6 induces human (h)AGT transcription activating signal transducers and activators (STATs). Here investigated coactivator p300/cAMP response element binding protein-binding protein (CBP) STAT3-mediated hAGT gene expression. Overexpression adenovirus 12S E1A, which binds inactivates p300/CBP, strongly...
ABSTRACT Respiratory syncytial virus (RSV) is a paramyxovirus that produces airway inflammation, in part by inducing interleukin-8 (IL-8) expression, CXC-type chemokine, via the NF-κB/RelA and STAT/IRF signaling pathways. In RSV-infected A549 cells, IL-8 transcription attenuates after 24 h spite of ongoing viral replication persistence nuclear RelA, suggesting mechanism for transcriptional attenuation. RSV infection induces B-cell lymphoma protein -3 (Bcl-3) expression 6 to 12 infection, at...
Chronic myelogenous leukemia (CML) results from a t(9,22) translocation, producing the p210BCR-ABL oncoprotein, tyrosine kinase that causes transformation and chemotherapy resistance. To further understand mechanisms mediating resistance, we identified 556 differentially regulated genes in HL-60 cells stably expressing p210BCR-ABLversus those an empty vector using cDNA macro- oligonucleotide microarrays. These BCR-ABL-regulated gene products play diverse roles cellular function including...
Abstract The capacity of adult human glial progenitor cells (AGPs), to proliferate and undergo multipotent differentiation, positions them as ideal candidate origin for gliomas. To investigate this potential role we identified AGPs mitotically active Olig2 in nonneoplastic brain We conservatively estimated that one 5,000 temporal lobe neocortical gray or subcortical white matter is mitotic. Extrapolating from a mean Olig2/Mib‐1 labeling index (LI) 52% total cell number 100 billion, the...
Abstract Background MYC amplification or overexpression is common in Group 3 medulloblastoma and associated with the worst prognosis. Recently, protein arginine methyl transferase (PRMT) 5 expression has been closely aberrant function various cancers, including brain tumors such as glioblastoma. However, role of PRMT5 its association have not explored. Here, we report a novel regulator implicate potential therapeutic target MYC-driven medulloblastoma. Methods Expression between primary were...