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Search Results: 1 - 10 of 22309 matches for " Jae-Woong Chang "
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Network-based Isoform Quantification with RNA-Seq Data for Cancer Transcriptome Analysis
Wei Zhang,Jae-Woong Chang,Lilong Lin,Kay Minn,Baolin Wu,Jeremy Chien,Jeongsik Yong,Hui Zheng,Rui Kuang
Computer Science , 2014,
Abstract: High-throughput mRNA sequencing (RNA-Seq) is widely used for transcript quantification of gene isoforms. Since RNA-Seq data alone is often not sufficient to accurately identify the read origins from the isoforms for quantification, we propose to explore protein domain-domain interactions as prior knowledge for integrative analysis with RNA-seq data. We introduce a Network-based method for RNA-Seq-based Transcript Quantification (Net-RSTQ) to integrate protein domain-domain interaction network with short read alignments for transcript abundance estimation. Based on our observation that the abundances of the neighboring isoforms by domain-domain interactions in the network are positively correlated, Net-RSTQ models the expression of the neighboring transcripts as Dirichlet priors on the likelihood of the observed read alignments against the transcripts in one gene. The transcript abundances of all the genes are then jointly estimated with alternating optimization of multiple EM problems. In simulation Net-RSTQ effectively improved isoform transcript quantifications when isoform co-expressions correlate with their interactions. qRT-PCR results on 25 multi-isoform genes in a stem cell line, an ovarian cancer cell line, and a breast cancer cell line also showed that Net-RSTQ estimated more consistent isoform proportions with RNA-Seq data. In the experiments on the RNA-Seq data in The Cancer Genome Atlas (TCGA), the transcript abundances estimated by Net-RSTQ are more informative for patient sample classification of ovarian cancer, breast cancer and lung cancer. All experimental results collectively support that Net-RSTQ is a promising approach for isoform quantification.
Network-Based Isoform Quantification with RNA-Seq Data for Cancer Transcriptome Analysis
Wei Zhang?,Jae-Woong Chang,Lilong Lin?,Kay Minn?,Baolin Wu?,Jeremy Chien?,Jeongsik Yong?,Hui Zheng?,Rui Kuang
PLOS Computational Biology , 2015, DOI: 10.1371/journal.pcbi.1004465
Abstract: High-throughput mRNA sequencing (RNA-Seq) is widely used for transcript quantification of gene isoforms. Since RNA-Seq data alone is often not sufficient to accurately identify the read origins from the isoforms for quantification, we propose to explore protein domain-domain interactions as prior knowledge for integrative analysis with RNA-Seq data. We introduce a Network-based method for RNA-Seq-based Transcript Quantification (Net-RSTQ) to integrate protein domain-domain interaction network with short read alignments for transcript abundance estimation. Based on our observation that the abundances of the neighboring isoforms by domain-domain interactions in the network are positively correlated, Net-RSTQ models the expression of the neighboring transcripts as Dirichlet priors on the likelihood of the observed read alignments against the transcripts in one gene. The transcript abundances of all the genes are then jointly estimated with alternating optimization of multiple EM problems. In simulation Net-RSTQ effectively improved isoform transcript quantifications when isoform co-expressions correlate with their interactions. qRT-PCR results on 25 multi-isoform genes in a stem cell line, an ovarian cancer cell line, and a breast cancer cell line also showed that Net-RSTQ estimated more consistent isoform proportions with RNA-Seq data. In the experiments on the RNA-Seq data in The Cancer Genome Atlas (TCGA), the transcript abundances estimated by Net-RSTQ are more informative for patient sample classification of ovarian cancer, breast cancer and lung cancer. All experimental results collectively support that Net-RSTQ is a promising approach for isoform quantification. Net-RSTQ toolbox is available at http://compbio.cs.umn.edu/Net-RSTQ/.
Emphysema is associated with increased inflammation in lungs of atherosclerosis-prone mice by cigarette smoke: implications in comorbidities of COPD
Gnanapragasam Arunachalam, Isaac K Sundar, Jae-woong Hwang, Hongwei Yao, Irfan Rahman
Journal of Inflammation , 2010, DOI: 10.1186/1476-9255-7-34
Abstract: Adult male and female wild-type (WT) mice of genetic background C57BL/6J and ApoE-/- mice were exposed to CS, and lung inflammatory responses, oxidative stress (lipid peroxidation products), mechanical properties as well as airspace enlargement were assessed.The lungs of ApoE-/- mice showed augmented inflammatory response and increased oxidative stress with development of distal airspace enlargement which was accompanied with decline in lung function. Interestingly, the levels and activities of matrix metalloproteinases (MMP-9 and MMP-12) were increased, whereas the level of eNOS was decreased in lungs of CS-exposed ApoE-/- mice as compared to air-exposed ApoE-/- mice or CS-exposed WT mice.These findings suggest that CS causes premature emphysema and a decline of lung function in mice susceptible to cardiovascular abnormalities via abnormal lung inflammation, increased oxidative stress and alterations in levels of MMPs and eNOS.Chronic obstructive pulmonary disease (COPD) is characterized by chronic airflow limitation resulting from excessive airway inflammatory response mediated by cigarette smoke (CS). Comorbidities such as cardiovascular disease, diabetes, lung cancer, and osteoporosis are more prevalent in smokers and patients with COPD [1-3]. Recent studies have shown that smokers with altered forced expiratory volume in one second (FEV1) and airflow limitation are associated with arterial stiffness, exaggerated atherosclerosis and vice-versa [2,4,5]. Growing evidence also indicates that inflammation, endothelial dysfunction and oxidative modification of lipids play an important role in the pathogenesis of atherosclerosis and COPD [3,6,7]. In addition to CS, alcohol consumption is also one among the important contributing factors involved in the pathogenesis of COPD and atherosclerosis and their co-morbidities [8,9].Apolipoprotein E-deficient (ApoE-/-) mice develop atherosclerosis due to an accumulation of cholesterol ester-enriched particles in the blood resul
NF-κB Inducing Kinase, NIK Mediates Cigarette Smoke/TNFα-Induced Histone Acetylation and Inflammation through Differential Activation of IKKs
Sangwoon Chung, Isaac K. Sundar, Jae-Woong Hwang, Fiona E. Yull, Timothy S. Blackwell, Vuokko L. Kinnula, Michael Bulger, Hongwei Yao, Irfan Rahman
PLOS ONE , 2011, DOI: 10.1371/journal.pone.0023488
Abstract: Background Nuclear factor (NF)-κB inducing kinase (NIK) is a central player in the non-canonical NF κB pathway, which phosphorylates IκB kinase α (IKKα) resulting in enhancement of target gene expression. We have recently shown that IKKα responds to a variety of stimuli including oxidants and cigarette smoke (CS) regulating the histone modification in addition to its role in NF-κB activation. However, the primary signaling mechanism linking CS-mediated oxidative stress and TNFα with histone acetylation and pro-inflammatory gene transcription is not well understood. We hypothesized that CS and TNFα increase NIK levels causing phosphorylation of IKKα, which leads to histone acetylation. Methodology To test this hypothesis, we investigated whether NIK mediates effects of CS and TNFα on histone acetylation in human lung epithelial cells in vitro and in lungs of mouse exposed to CS in vivo. CS increased the phosphorylation levels of IKKα/NIK in lung epithelial cells and mouse lungs. NIK is accumulated in the nuclear compartment, and is recruited to the promoters of pro-inflammatory genes, to induce posttranslational acetylation of histones in response to CS and TNFα. Cells in which NIK is knocked down using siRNA showed partial attenuation of CSE- and TNFα-induced acetylation of histone H3 on pro-inflammatory gene promoters. Additional study to determine the role of IKKβ/NF-κB pathway in CS-induced histone acetylation suggests that the canonical pathway does not play a role in histone acetylation particularly in response to CS in mouse lungs. Conclusions Overall, our findings provide a novel role for NIK in CS- and TNFα-induced histone acetylation, especially on histone H3K9.
Mitogen- and Stress-Activated Kinase 1 (MSK1) Regulates Cigarette Smoke-Induced Histone Modifications on NF-κB-dependent Genes
Isaac K. Sundar, Sangwoon Chung, Jae-woong Hwang, John D. Lapek, Michael Bulger, Alan E. Friedman, Hongwei Yao, James R. Davie, Irfan Rahman
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0031378
Abstract: Cigarette smoke (CS) causes sustained lung inflammation, which is an important event in the pathogenesis of chronic obstructive pulmonary disease (COPD). We have previously reported that IKKα (I kappaB kinase alpha) plays a key role in CS-induced pro-inflammatory gene transcription by chromatin modifications; however, the underlying role of downstream signaling kinase is not known. Mitogen- and stress-activated kinase 1 (MSK1) serves as a specific downstream NF-κB RelA/p65 kinase, mediating transcriptional activation of NF-κB-dependent pro-inflammatory genes. The role of MSK1 in nuclear signaling and chromatin modifications is not known, particularly in response to environmental stimuli. We hypothesized that MSK1 regulates chromatin modifications of pro-inflammatory gene promoters in response to CS. Here, we report that CS extract activates MSK1 in human lung epithelial (H292 and BEAS-2B) cell lines, human primary small airway epithelial cells (SAEC), and in mouse lung, resulting in phosphorylation of nuclear MSK1 (Thr581), phospho-acetylation of RelA/p65 at Ser276 and Lys310 respectively. This event was associated with phospho-acetylation of histone H3 (Ser10/Lys9) and acetylation of histone H4 (Lys12). MSK1 N- and C-terminal kinase-dead mutants, MSK1 siRNA-mediated knock-down in transiently transfected H292 cells, and MSK1 stable knock-down mouse embryonic fibroblasts significantly reduced CS extract-induced MSK1, NF-κB RelA/p65 activation, and posttranslational modifications of histones. CS extract/CS promotes the direct interaction of MSK1 with RelA/p65 and p300 in epithelial cells and in mouse lung. Furthermore, CS-mediated recruitment of MSK1 and its substrates to the promoters of NF-κB-dependent pro-inflammatory genes leads to transcriptional activation, as determined by chromatin immunoprecipitation. Thus, MSK1 is an important downstream kinase involved in CS-induced NF-κB activation and chromatin modifications, which have implications in pathogenesis of COPD.
Alpha 1,3-Galactosyltransferase Deficiency in Pigs Increases Sialyltransferase Activities That Potentially Raise Non-Gal Xenoantigenicity
Jong-Yi Park,Mi-Ryung Park,Deug-Nam Kwon,Min-Hui Kang,Mihye Oh,Jae-Woong Han,Ssang-Goo Cho,Chankyu Park,Dong-Ku Kim,Hyuk Song,Jae-Wook Oh,Jin-Hoi Kim
Journal of Biomedicine and Biotechnology , 2011, DOI: 10.1155/2011/560850
Abstract: We examined whether deficiency of the GGTA1 gene in pigs altered the expression of several glycosyltransferase genes. Real-time RT-PCR and glycosyltransferase activity showed that 2 sialyltransferases [α2,3-sialyltransferase (α2,3ST) and α2,6-sialyltransferase (α2,6ST)] in the heterozygote GalT KO liver have higher expression levels and activities compared to controls. Enzyme-linked lectin assays indicated that there were also more sialic acid-containing glycoconjugate epitopes in GalT KO livers than in controls. The elevated level of sialic-acid-containing glycoconjugate epitopes was due to the low level of α-Gal in heterozygote GalT KO livers. Furthermore, proteomics analysis showed that heterozygote GalT KO pigs had a higher expression of NAD
Efficacies of the new Paclitaxel-eluting Coroflex Please? Stent in percutaneous coronary intervention; comparison of efficacy between Coroflex Please? and Taxus? (ECO-PLEASANT) trial: study rationale and design
Jae-Bin Seo, Hui-Kyung Jeon, Kyung-Woo Park, Jong-Seon Park, Jang-Ho Bae, Sang-Wook Kim, Keon-Woong Moon, Jae-Woong Choi, Sang-Gon Lee, Woo-Young Chung, Tae-Jin Youn, Soo-Joong Kim, Doo-Il Kim, Byung-Ok Kim, Min-Su Hyon, Keum-Soo Park, Tae-Joon Cha, Hweung-Kon Hwang, Seung-Ho Hur, Hyo-Soo Kim
Trials , 2009, DOI: 10.1186/1745-6215-10-98
Abstract: In the comparison of Efficacy between COroflex PLEASe? ANd Taxus? stent(ECO-PLEASANT) trial, approximately 900 patients are being prospectively and randomly assigned to the either type of Coroflex Please? stent and Taxus Liberte? stent via web-based randomization. The primary endpoint is clinically driven target vessel revascularization at 9 months. The secondary endpoints include major cardiac adverse events, target vessel failure, stent thrombosis and angiographic efficacy endpoints.The ECO-PLEASANT trial is the study not yet performed to directly compare the efficacy and safety of the Coroflex Please? versus Taxus Liberte? stent. On the basis of this trial, we will be able to find out whether the Coroflex Please? stent is non-inferior to Taxus Liberte? stent or not.ClinicalTrials.gov number, NCT00699543.Previous randomized trials have shown the efficacy of a slow-release polymeric sirolimus-eluting stent (Cypher?, Cordis, Warren, NJ, USA), paclitaxel-eluting stent (Taxus?, Boston Scientific, Natick, MA, USA), and zotarolimus-eluting stent (Endeavor?, Medtronic, Minneapolis, MN, USA) over bare metal stents in reducing neointimal hyperplasia, late luminal loss, and angiographic restenosis leading to decreased target lesion revascularization [1-11] The Paclitaxel-eluting Coroflex Please? stent is a newly developed drug eluting stent using the Coroflex? stent platform combined with the drug paclitaxel contained in a polymer coating[12]In the PECOPS I, which was one-arm observational study, the results of Coroflex Please? stent were within the range of other Paclitaxel-eluting coronary stents [12,13] Compared with binary restenosis rate of 7.9% in Taxus IV trial, Coroflex? Please stent showed 7.8% of restenosis rate[7] The 3.1% of 30 day MACE rate is within the range of other trials with stents eluting Paclitaxel or Sirolimus. The 6 month MACE rates in PECOPS I were 8.0%, which was similar to 7.8%, and 8.5% in Taxus II MR and SR, respectively[6] In Taxus IV, 9 month f
Relationship between cyclooxygenase 8473T>C polymorphism and the risk of lung cancer: a case-control study
Jung Park, Jin Choi, Myung Chae, Won Lee, Sung Cha, Ji-Woong Son, Chang Kim, Sin Kam, Young Kang, Tae Jung, Jae Park
BMC Cancer , 2006, DOI: 10.1186/1471-2407-6-70
Abstract: The COX-2 genotypes were determined using PCR-based primer-introduced restriction analysis in 582 lung cancer patients and in 582 healthy controls that were frequency-matched for age and gender.The distribution of the COX-2 8473T>C genotypes was not significantly different between the overall lung cancer cases and the controls. However, when the cases were categorized by the tumor histology, the combined 8473 TC + CC genotype was associated with a significantly decreased risk of adenocarcinoma as compared with the 8473 TT genotype (adjusted OR = 0.64; 95% CI = 0.46–0.90, P = 0.01). On the stratification analysis, the protective effect of the combined 8473 TC + CC genotype against adenocarcinoma was statistically significant in the males, older individuals and ever-smokers (adjusted OR = 0.59; 95% CI = 0.39–0.91, P = 0.02; adjusted OR = 0.55; 95% CI = 0.33–0.93, P = 0.03; and adjusted OR = 0.57; 95% CI = 0.37–0.87, P = 0.01, respectively).These findings suggest that the COX-2 8473T>C polymorphism could be used as a marker for the genetic susceptibility to adenocarcinoma of the lung.Although cigarette smoking is the major cause of lung cancer, only a fraction of smokers develop lung cancer during their lifetime, and this suggests that genetic factors are of importance in determining an individual's susceptibility to lung cancer [1].Cyclooxygenase (COX, also known as prostanglandin endoperoxide synthase) is the rate-limiting enzyme for the production of prostaglandins (PGs) from free arachidonic acid. Two isoforms of COX have been identified. COX-1 is constitutively expressed in most normal tissues and it is considered to be a housekeeping enzyme that is responsible for various physiologic functions. In contrast, COX-2 is rarely expressed in normal tissues, but it is rapidly induced in response to cytokines, growth factors and tumor promoters [2. 3]. Overexpression of COX-2 has been reported in a variety of human malignancies, including lung cancer [4-6]. Up-regulation
Inhibition of PCAF Histone Acetyltransferase, Cytotoxicity and Cell Permeability of 2-Acylamino-1-(3- or 4-Carboxy-phenyl)benzamides
Woong Jae Park,Eunsook Ma
Molecules , 2012, DOI: 10.3390/molecules171113116
Abstract: Small molecule HAT inhibitors are useful tools to unravel the role of histone acetyltransferases (HATs) in the cell and they also have relevance in oncology. We synthesized a series of 2-acylamino-1-(3- or 4-carboxyphenyl)benzamides 8–19 bearing C6, C8, C10, C12, C14, and C16 acyl chains at the 2-amino position of 2-aminobenzoic acid. Enzyme inhibition of these compounds was investigated using in vitro PCAF HAT assays. The inhibitory activities of compounds 8–10, 16, and 19 were similar to that of anacardic acid, and 17 was found to be more active than anacardic acid at 100 μM. Compounds 11–15 showed the low inhibitory activity on PCAF HAT. The cytotoxicity of the synthesized compounds was evaluated by SRB (sulforhodamine B) assay against seven human cancer cell lines: HT-29 (colon), HCT-116 (colon), MDA-231 (breast), A549 (lung), Hep3B (hepatoma), HeLa (cervical) and Caki (kidney) and one normal cell line (HSF). Compound 17 was more active than anacardic acid against human colon cancer (HCT 116, IC50: 29.17 μM), human lung cancer (A549, IC50: 32.09 μM) cell lines. 18 was more active than anacardic acid against human colon cancer (HT-29, IC50: 35.49 μM and HCT 116, IC50: 27.56 μM), human lung cancer (A549, IC50: 30.69 μM), and human cervical cancer (HeLa, IC50: 34.41 μM) cell lines. The apparent permeability coefficient (Papp, cm/s) values of two compounds (16 and 17) were evaluated as 68.21 and 71.48 × 10?6 cm/s by Caco-2 cell permeability assay.
A case of hypereosinophilic syndrome presenting with intractable gastric ulcers
Tae Young Park, Chang Hwan Choi, Suh Yoon Yang, In Soo Oh, In-Do Song, Hyun Woong Lee, Hyung Joon Kim, Jae Hyuk Do, Sae Kyung Chang, Ah Ra Cho, Young Joo Cha
World Journal of Gastroenterology , 2009,
Abstract: We report a rare case of hypereosinophilic syndrome (HES) presenting with intractable gastric ulcers. A 71-year-old man was admitted with epigastric pain. Initial endoscopic findings revealed multiple, active gastric ulcers in the gastric antrum. He underwent Helicobacter pylori (H pylori) eradication therapy followed by proton pump inhibitor (PPI) therapy. However, follow-up endoscopy at 4, 6, 10 and 14 mo revealed persistent multiple gastric ulcers without significant improvement. The proportion of his eosinophil count increased to 43% (total count: 7903/mm3). Abdominal-pelvic and chest computed tomography scans showed multiple small nodules in the liver and both lungs. The endoscopic biopsy specimen taken from the gastric antrum revealed prominent eosinophilic infiltration, and the liver biopsy specimen also showed eosinophilic infiltration in the portal tract and sinusoid. A bone marrow biopsy disclosed eosinophilic hyperplasia as well as increased cellularity of 70%. The patient was finally diagnosed with HES involving the stomach, liver, lung, and bone marrow. When gastric ulcers do not improve despite H pylori eradication and prolonged PPI therapy, infiltrative gastric disorders such as HES should be considered.
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