A5088186001- Chromatin Remodeling and Cancer
- Mechanisms of cancer metastasis
- MicroRNA in disease regulation
- Cytokine Signaling Pathways and Interactions
- Cancer Mechanisms and Therapy
- Glioma Diagnosis and Treatment
- Circular RNAs in diseases
- Cancer-related molecular mechanisms research
- Ferroptosis and cancer prognosis
- Endoplasmic Reticulum Stress and Disease
- RNA regulation and disease
- Ubiquitin and proteasome pathways
- interferon and immune responses
- Cancer, Hypoxia, and Metabolism
- Protein Tyrosine Phosphatases
- Epigenetics and DNA Methylation
- Microtubule and mitosis dynamics
- Cancer-related Molecular Pathways
- Radiomics and Machine Learning in Medical Imaging
- RNA Interference and Gene Delivery
- Melanoma and MAPK Pathways
- NF-κB Signaling Pathways
- Immune Response and Inflammation
- PI3K/AKT/mTOR signaling in cancer
- DNA Repair Mechanisms
The Ohio State University
2015-2025
The Ohio State University Wexner Medical Center
2015-2025
The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute
2015-2023
Columbus Oncology and Hematology Associates
2015
Dhaka Medical College and Hospital
2014
Cleveland Clinic Lerner College of Medicine
2003-2013
Cleveland Clinic
1999-2010
Institute of Molecular Medicine
1997-2003
The Honourable Society of Lincoln's Inn
1997
University of North Carolina at Chapel Hill
1993-1996
Human respiratory epithelium expresses inducible nitric oxide synthase (iNOS) continuously in vivo, however mechanisms responsible for maintenance of expression are not known. We show that IFNgamma is sufficient induction iNOS primary human airway epithelial cells (HAEC) vitro, and IL-4 potentiates IFNgamma-induced HAEC through stabilization mRNA. IFNgamma/IL-4- induced was delayed onset prolonged with up to 1 wk. Removal overlying culture media resulted loss expression, while transfer...
Binding of interleukin (IL)-4 to its transmembrane receptor results in the Jak-mediated tyrosine phosphorylation a number protein components IL-4 signaling cascade, including Jak1, Jak2, Jak3, Tyk2, IL-4Rα, IRS-1, IRS-2, and Stat6 appropriate cell types. However, protein-tyrosine phosphatases (PTPs) that dephosphorylate these proteins terminate remained unidentified. We have noted IL-4-dependent activation is sustained longer fibroblasts than lymphoid cells. Because Shp-1, an SH2...
Abstract The IFN-inducible dsRNA-activated protein kinase PKR regulates synthesis through phosphorylation of eukaryotic initiation factor-2α. It also acts as a signal transducer for transcription factors NF-κB, IFN regulatory factor-1, and activating factor-2. IFN-γ, pleiotropic cytokine, elicits gene expression by the Janus kinase-STAT signaling pathway. IFN-γ can synergize with TNF-α to activate NF-κB in number cell lines. Here we show that alone kinase-1-mediated, but Stat1-independent,...
Interleukin (IL)-4 exhibits antitumor activity in rodent experimental gliomas, which is likely mediated by the actions of IL-4 on a variety immune cells present and around tumor masses. Here, we show that IL-4, activates Stat6 normal human astrocytes other cells, induces an aberrant activation Stat3 glioblastoma multiforme (GBM) but not astrocytes. Previously, have shown autocrine IL-6 signaling persistent Stat3. Now, further activated stimulation GBM cells. Expression IL-13Ralpha2, decoy...
Different Stat proteins are activated through phosphorylation of unique tyrosine residues in response to different cytokines and growth factors. Interferon-gamma activates Stat1 molecules that form homodimers bind cognate DNA elements. Here we show treatment permeabilized cells with 200-500 microM peroxo-derivatives vanadium, molybdenum, tungsten results the accumulation constitutively phosphorylated alpha molecules. In contrast, orthovanadate, vanadyl sulfate, molybdate, tungstate at same...
Purpose: Over 90% of pancreatic adenocarcinoma PC express oncogenic mutant KRAS that constitutively activates the Raf-MEK-MAPK pathway conferring resistance to both radiation and chemotherapy. MEK inhibitors have shown promising anti-tumor responses in recent preclinical clinical studies, are currently being tested combination with trials. Here, we evaluated radiosensitizing potential a novel MEK1/2 inhibitor GSK1120212 (GSK212,or trametinib) whether inhibition alters DNA repair mechanisms...
Osteoclast formation is dependent on the ability of TGF-beta to enable receptor activator NF-kappaB ligand (RANKL)-induced commitment hemopoietic precursors osteoclastic lineage. The mechanism by which enables unknown. One possibility that opposes Janus kinase (JAK)/STAT signals generated inhibitory cytokines such as IFN-beta. JAK/STAT pathway activated induce resistance osteoclast formation, IFN-gamma and M-CSF, effect these opposed TGF-beta. Recently, a group STAT-induced factors, termed...
Transcriptional activation of genes containing the interferon (1FN)-stimulated response element (ISRE) by IFN-a is known to be mediated through post-translational IFN-stimulated gene factor 3 (ISGF3) and its subsequent interactions with ISRE.W e have identified an ISRE-ISGF34ndependent signaling pathway used for induction IFN regulatory 1 (IRF-1) gene.A minimal functional promoter IRF-1 does not contain ISRE, but we shown that transcription activated in cell lines do produce ISGF3 activity...
Exposure of cells to protein tyrosine phosphatase (PTP) inhibitors causes an increase in the phosphotyrosine content many cellular proteins. However, level at which primary signaling event is affected still unclear. We show that Jaks are activated by phosphorylation briefly exposed PTP inhibitor pervanadate (PV), resulting and functional activation Stat6 (in addition other Stats). Mutant cell lines lack Jak1 activity fail support PV-mediated [or interleukin 4 (IL-4)-dependent] but can be...
Cystic fibrosis (CF) airway epithelial cells are more susceptible to viral infection due impairment of the innate host defense pathway nitric oxide (NO). NO synthase-2 (NOS2) expression is absent, and signal transducer activator transcription (STAT) 1 activation reduced in CF. We hypothesized that IFN-gamma signaling pathway, which leads NOS2 gene induction CF cells, defective. In contrast a lack induction, major histocompatibility complex class 2, an IFN-gamma-regulated delayed-responsive...
Lung cancer stands as the leading cause of cancer-related death worldwide, impacting both men and women in United States beyond. Radiation therapy (RT) serves a key treatment modality for various lung malignancies. Our study aims to systematically assess prognosis influence RT on metabolic reprogramming patients diagnosed with nonsmall-cell (NSCLC) through longitudinal profiling. A cohort 54 NSCLC underwent thoracic radiotherapy, 96% receiving total radiation dose ranging from 40 70 Gy,...
Abstract Objective: Despite aggressive treatment with surgery, radiation and temozolomide chemotherapy glioblastoma (GBM) remains the most lethal tumor of human brain, which is largely due to inevitable recurrence refractory tumor. Studies have shown that aberrant activation AKT significantly contributes development resistance in GBM. Molecular profiling vitro studies from our group identified TAGLN2, an actin binding cytoskeletal protein, as a top upregulated gene In other cancer types,...
Suppressor of cytokine signaling (SOCS) family proteins were originally identified as cytokine-induced negative regulators signaling. We show that SOCS-1 and SOCS-3 inhibit interleukin (IL)-4-dependent signal transducer activator transcription 6 (Stat6) activation subsequent gene induction. By contrast, SOCS-2 cytokine-inducible Src homology domain 2 (SH2)-containing protein up-regulate these processes. IL-4 initiates transmembrane through two types receptor complexes comprising the IL-4Rα...
Mast cells (MCs) are found in increased numbers at airway mucosal surfaces asthmatic patients. Because human epithelial (HAECs) actively participate inflammatory responses and direct contact with MCs the mucosa, we hypothesized that HAEC-MC interactions may contribute to differentiation survival of mucosa. Here, show HAECs express mRNA protein for soluble membrane-bound stem cell factor, releasing factor into culture supernatant a concentration 5.9 ± 0.1 ng per 10 6 HAEC. were able support...
Interferon-γ (IFN-γ) is required for induction of the human nitric oxide synthase-2 ( NOS2) gene in lung epithelium. Although NOS2 promoter region contains many cytokine-responsive elements, molecular basis only partially understood. Here, major cis-regulatory elements that control IFN-γ-inducible transcription epithelial cells are identified as composite response bind signal transducer and activator 1 (STAT-1) protein (AP-1), which comprised c-Fos, Fra-2, c-Jun, JunD. Notably, IFN-γ...
The UDP glucuronosyltransferase gene UGT2B2 is constitutively expressed in rat liver, and the enzyme has been shown to conjugate glucuronic acid with various endogenous steroids, especially etiocholanolone androsterone. We have cloned sequenced much of 5'-flanking (247 bp) 3'-flanking (734 regions. contains six exons spanning about 15.3 kb. Translation begins at nucleotide 36 exon 1 terminates 280 coding nucleotides into 6, encoding a protein 530 amino acids (calculated Mr unmodified chain =...