title: To evaluate the effect of Terminalia arjuna as an adjuvant therapy in subjects with stable coronary artery disease on standard dosage regimens versus placebo

status: Public on Apr 16 2015

city: Bangalore

first: madavan

last: vasudevan

state: Karnataka

address: Kasturi Nagar

country: India

institute: Theomics International Private Limited

summary: Terminalia arjuna (Roxb.) Wight & Arn., a well known Traditional medicine an. popularly known as Arjuna, has a long antiquity of its role as a cardiac stimulant, and has been stipulated in the treatment of hypercholesterolemia, heart failure and atherosclerosis. The present study was carried out to access the effects of Terminalia arjuna as an adjuvant therapy in angiographically proven patients with stable coronary artery disease who were on conventional medications. The goal of the study was to establish whether Terminalia arjuna exerts beneficial effects in targetting disease signatures which remain unresponsive to the standard therapies currently employed in the clinics. The present study scientifically validates the therapeutic effects of this medicinal plant as an adjuvant therapy along with conventional drugs routinely used in the clinics for prevention and treatment of coronary artery disease.

overall_design: To access the effect of T.arjuna, a placebo-controlled, double blind randomized study was carried out in 100 angiographically proven non-diabetic patients with coronary artery disease having disease more than 3 months prior to their enrollment and using any combination of cardiac-related medications including ASA, ACEIs, ARBs, β-blockers and statins (Trial Registration Number : REF/2013/03/004810). Out of total 100 patients, 50 patients were on drug A and 50 patients were on drug B for a total duration of 6 months (Follow-up at 3 and 6 months). Both Drug as well as placebo was given in the form of capsule (500mg) provided by The Himalaya Drug Company, Bangalore. Method of concealment was through coded identical containers. All the participants, investigator, outcome Assessor and data-entry operator were blinded during the whole study. Micro-array was performed in 2 randomly selected patients in each sub-group i.e. Terminalia arjuna or Placebo at 3 and 6 months respectively. RNA extraction and hybridization was carried out using Affymetrix microarrays. Differential expression of genes in T.arjuna-treated and Placebo groups was studied to understand the specificity, efficacy and mechanism of action of T.arjuna.

first: Divya

last: Kapoor

first: Veena

last: Dhawan

first: Rajesh

last: Vijayvergiya

first: Deepak

last: Kaul

first: K

last: Parashar


title: Microarray analysis to identify differential molecular signatures in subjects with stable coronary artery disease on standard dosage regimens versus healthy controls

summary:
In the present study, we used a top-down approach using microarray analysis to evaluate the novel molecular signatures that differentiate between subjects with stable coronary artery disease and normal healthy controls and which remain unresponsive to the standard therapies currently in clinical practice .
Micro-array analysis revealed that inspite of concerted treatment efforts 513 genes were differentially expressed in our patient group vs healthy controls.

overall_design: To access the effect of ongoing therapies on stable CAD patients and to obtain gene signatures from these patients. We selected 4 angiographically proven stable CAD patients who were on medications for more than 3 months or more from Group-1 (n=100) and compared the data with 2 normal age and sex-matched healthy Controls (n=50) belonging to the same ethnic origin and socio-economic status. RNA extraction and hybridization was done using Affymetrix microarrays.

middle: K


title: Comparison of gene expression levels in parental U87 cells and U87 tumor spheres treated with or without ITE

status: Public on Apr 18 2015

city: Hangzhou

first: Yingjie

last: Wang

state: Zhejiang

address: Research Center C701,School of Medicine,Zhejiang University,866 Yuhangtang Road

department: Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, the First Affiliated Hospital, School of Medicine

country: China

institute: Zhejiang University

summary:
The formation of U87 tumor spheres was associated with expression changes of many genes which was reverted by the treatment with ITE(2-(1'H-indole-3'-carbonyl)-thiazole-4-carboxylic acid methyl ester).
We used DNA microarrays to profile gene expression in U87 tumor spheres treated with ITE and identified distinct classes of up-regulated and down-regulated genes during this process.

overall_design: U87 cells were selected for RNA extraction and hybridization on Affymetrix microarrays. We compared the expression profiles of parental U87 cells, U87 tumor sphere cells treated with vehicle (DMSO) and U87 tumor sphere cells treated with ITE.

first: Wang

last: Ying-Jie

first: Kang

last: Bo


title: Gene expression data following heptose-bisphosphate (HBP) treatment of Jurkat T cells

status: Public on Apr 15 2015

city: Toronto

first: Scott

middle: D.

last: Gray-Owen

state: Ontario

address: 1 King's College Circle

department: Molecular Genetics

country: Canada

institute: University of Toronto

summary:
Host recognition of pathogen-associated molecular patterns (PAMPs) initiates an innate immune response that is critical for pathogen elimination and engagement of adaptive immunity. Here we show that mammalian cells can detect and respond to the bacterial-derived monosaccharide heptose-1,7-bisphosphate (HBP). A metabolic intermediate in lipopolysaccharide (LPS) biosynthesis, HBP is highly conserved in Gram-negative bacteria, yet absent from eukaryotic cells. Detection of HBP within the host cytosol activated the NF-κB pathway in vitro, and induced innate and adaptive immune responses in vivo. Moreover, we used a genome-wide RNAi screen to uncover an innate immune signaling axis, mediated by phosphorylation-dependent oligomerization of the TRAF-interacting protein with forkhead-associated domain (TIFA) that is triggered by HBP. Thus, HBP is a PAMP that activates TIFA-dependent immunity to Gram-negative bacteria.
We used a microarray to characterize the gene expression signature induced by HBP.

overall_design: We treated two clonal Jurkat T cell lines with culture supernatants prepared from N. gonorrhoeae, a HBP shedding Gram-negative bacteria, or M. catarrhalis, a naturally HBP deficient Gram-negative bacteria. Genes upregulated by N. gonorrhoeae supernatants compared to M. catarrhalis supernatants were considered induced by HBP

first: Ryan

middle: G

last: Gaudet

middle: D


title: In vivo oncogenomics screen identifies novel ependymoma oncogenes and tumor suppressor genes within large chromosomal alterations

status: Public on Apr 28 2015

city: Memphis

first: David

last: Finkelstein

state: TN

address: 332 N. Lauderdale St.

department: Computational Biology

country: USA

institute: St Jude Children's Research Hospital

summary: Cancers are characterized by non-random, chromosome copy number variations that presumably contain oncogenes and tumor suppressor genes (TSGs).  The affected loci are often large, making it difficult to pinpoint which genes are driving the cancer.  Here, we report a cross-species, in vivo screen of 84 candidate oncogenes and 39 candidate TSGs, located within 28 recurrent chromosomal alterations in ependymoma.  Through a series of mouse models we validate eight new ependymoma oncogenes and 11 TSGs that dysregulate a small number of cell functions including vesicle trafficking and cholesterol biosynthesis; pinpointing these as potential points for therapeutic intervention.

overall_design: Mouse cortical tumors were excised.  These tumors derived from cells expressing one of 3  genes: RAB3A, BC74C, or ZNF668

first: Kumarasamypet

middle: M

last: Mhankumar

middle: S

last: Currle

first: Elsie

last: White

first: Nidal

last: Boulos

first: Jason

last: Dapper

first: Christopher

last: Eden

first: Birgit

last: Nimmervoll

first: Radhika

last: Thiruvenkatam

first: Michele

last: Connelly

first: Tanya

middle: A

last: Kranenburg

first: Geoffrey

last: Neale

last: Olsen

first: Yong-Dong

first: Karen

last: Wright

first: Kirti

last: Gupta

middle: W

last: Ellison

first: Arzu

middle: O

last: Thomas

first: Richard

middle: J

last: Gilbertson


title: Gene expression in primary human macrophages and foam cells

status: Public on Apr 08 2015

city: Oxford

last: O'Callaghan

state: Oxfordshire

address: Roosevelt Drive

department: Nuffield Department of Medicine

country: United Kingdom

institute: University of Oxford

summary: The aim of the experiment was to determine the effects of 48 hours of treatment with oxidized low density lipoprotein (oxLDL) on gene expression in primary human monocyte-derived macrophages.

overall_design:
6 independent biological replicates were processed. From each replicate half of the cells were treated with oxLDL and the other half were treated with the control buffer.
For foam cell formation (after 7 days) macrophages were treated with oxLDL (50mcg/ml, enodtoxin free, Copper oxidized). Control macrophages were treated with a matching buffer without oxLDL. Treatment duration - 48 hours.

first: Michael

middle: E

last: Reschen


title: LKB1 regulates the transcriptome of immortalized endometrial cells

city: Dallas

first: Diego

middle: H

last: Castrillon

state: TX

address: 5323 Harry Hines Boulevard

department: Pathology

institute: UT Southwestern Medical Center

summary: List of differentially-expressed transcripts following LKB1 knockdown with two non-overlapping shRNA constructs.

overall_design: Immortalized endometrial cells were stably transfected with two non-overlapping shRNA constructs (408-shRNA1, 409-shRNA2) and a non-target reference control (NT).  RNA was harvested from dividing cells and loaded onto the Illumina HumanHT-12 v4 Expression BeadChip.

last: Peña


title: PI3K inhibition results in enhanced estrogen receptor function and dependence in hormone receptor-positive breast cancer

status: Public on Apr 29 2015

city: Barcelona

first: Aleix

last: Prat

address: Passeig Vall d´Hebron 119

department: Translational Genomics

country: Spain

institute: VHIO

summary: Activating mutations of PIK3CA are the most frequent genomic alterations in estrogen receptor (ER)-positive breast tumors and selective PI3Kα inhibitors are in clinical development. The activity of these agents, however, is not homogenous and only a fraction of patients bearing PIK3CA-mutant ER-positive tumors benefit from single agent administration. Searching for mechanisms of resistance, we observed that suppression of PI3K signaling with different agents results in induction of ER-dependent transcriptional activity as demonstrated by changes in expression in genes containing ER binding sites, enhanced ER transcription and increased occupancy by the ER of promoter regions of upregulated genes. Furthermore, expression of ESR1 mRNA and ER protein levels themselves were also increased upon PI3K inhibition. These changes in gene expression were confirmed in vivo in xenograft and patient derived models and in tumors from patients undergoing treatment with the PI3Kα inhibitor BYL719. The observed effects on transcription were enhanced by the addition of estradiol and suppressed by the anti-ER therapies fulvestrant and tamoxifen. Fulvestrant markedly sensitized ER-positive tumors to PI3Kα inhibition. We propose that increased ER transcriptional activity may be a compensatory mechanism that limits the activity of PI3K inhibitors and that combined PI3K and ER inhibition is a rational approach to target these tumors.

overall_design: The aim of our study was to explore the mechanism by which combination of PI3K pathway inhibitors and estrogen receptor function blockade results in superior antitumor activity. We aimed to evaluate whether changes in ER function were influencing the clinical response to anti-PI3K therapy in ER-positive breast tumors that harbor PI3K pathway activation. For this purpose, we planned to use various specific PI3K inhibitors, namely: BYL719 (p110α specific catalytic inhibitor), GDC0941 (pan-PI3K inhibitor), GDC0032 and BAY80-6946 (p110sparing PI3K inhibitors) in a panel of ER-positive breast cancer cell lines and xenografts that harbor PIK3CA activating mutations. We also used MK2206 (pan-AKT allosteric inhibitor) to inhibit the PI3K pathway in ER-positive cell lines which activate this pathway through PTEN loss. Finally, in order to evaluate the role of ER up-regulation as a pro-survival signal in our in vitro and in vivo models, we planned to use the selective ER modulator 4-hydroxy-tamoxifen (4-OHT) and degrader fulvestrant. For the in vivo experiments, the number of animals in each group was calculated to measure a 25% difference between the means of placebo and treatment groups with a power of 80% and a p value of 0.01. Host mice carrying xenografts were randomly and equally assigned to either control or treatment groups. Animal experiments were conducted in a controlled and non-blinded manner. Moreover, we evaluated by means of RNAseq gene expression changes breast cancer patients that underwent BYL719 based therapy to validate our in vitro findings in terms of ER expression.   In vitro experiments were performed at least two times and at least in triplicate for each replica.

first: Maurizio

last: Scaltriti

first: Jose

last: Baselga


title: EIF3B knockdown

status: Public on Apr 07 2015

city: Nanchang

first: Jian-feng

last: Zheng

state: Jiangxi

address: No.1 Min De Road

institute: Nanchang University

summary: Eukaryotic translation initiation factor 3B (EIF3B) knockdown in SMMC-7721 cells

overall_design: EIF3B vs. Scramble siRNA

first: Xiao-he

last: Jiang

first: Xiao-zhong

last: Wang

first: Wu-hua

last: Guo

first: Ji-xiang

last: Zhang


title: Network analysis of gene expression in mice provides new evidence of involvement of the mTOR pathway in antipsychotic-induced extrapyramidal symptoms

status: Public on Apr 09 2015

first: Sergi

last: Mas Herrero

state: Catalunya

address: Casanova 143

department: Pharmacology, School of Medicine

institute: University of Barcelona

summary:
To identify potential candidate genes for future pharmacogenetic studies of antipsychotic (AP)-induced extrapyramidal symptoms (EPS), we used gene expression arrays to analyze changes induced by risperidone in mice strains with different susceptibility to EPS
This study is a part of a convergent functional genomic approach that plans to integrate the data presented here with: data from gene expression analysis of neuroblastoma cell line under treatment with risperidone; and data from gene expression analysis of peripheral blood from first psychotic patients treated with risperidone.

overall_design: Gene expression was assessed by microarray (Affymetrix GeneChip® Arrays MG 430 PM) in mice treated with risperidone 1mg/kg for three consecutive days

last: Mas

first: Patricia

last: Gassò

first: Amalia

last: Lafuente


title: Tumorigenic-enriched (TE) and lung-metastatic (LM) derivatives and parental populations from the breast cancer MDA-MB-231 and CN34 cell lines

status: Public on Apr 02 2015

city: New York

first: Jason

last: Ross

state: New York

address: 1230 York Ave

department: Systems Cancer Biology

institute: The Rockefeller University

summary: The LM2 derivative cell line is described in Minn et al. Nature 2005. The LM1a derivative cell line is described in Tavazoie et al. Nature 2008.

overall_design: Tumorigenic-enriched (TE) and lung-metastatic (LM) derivatives and their respective parental populations, from the breast cancer MDA-MB-231 and CN34 cell lines were transcriptomically compared in order to identify candidate regulators of breast cancer tumor re-initiation.

middle: B

first: Doowon

last: Huh

first: Lisa

last: Noble

first: Sohail

middle: F

last: Tavazoie


title: Diverse Targets of β-catenin during the Epithelial-Mesenchymal Transition Define Cancer Stem Cells and Predict Disease Relapse

status: Public on Apr 04 2015

city: Hsinchu

first: Jia-Lin

last: Lee

address: 101, Sec. 2, Kuang Fu Road

country: Taiwan

institute: National Tsing Hua University

summary: Wnt signaling contributes to the reprogramming and maintenance of cancer stem cell (CSC) states that is activated by the epithelial-mesenchymal transition (EMT) program. However, the mechanistic relationship between the EMT and Wnt pathway in CSCs remains unclear. Chromatin immunoprecipitation with high-throughput sequencing (ChIP-seq) indicated that EMT induces a switch from the β-catenin/E-cadherin/Sox15 complex to the β-catenin/Twist1/TCF4 complex, which then binds to CSC-related gene promoters. In tandem co-IP and re-ChIP experiments using epithelial-type cells, Sox15 associated with the β-catenin/E-cadherin complex and then bound to the proximal promoter region of CASP3, consequently resulting in Twist1 cleavage and negatively regulating the β-catenin–elicited promotion of the CSC phenotype. During the EMT, Twist1 in complex with β-catenin enhanced β-catenin/TCF4 transcriptional activity, which includes binding to the proximal promoter region of ABCG2, a marker of CSCs. For clinical application, the five-gene signature nuclear β-cateninHigh/nuclear Twist1High/E-cadherinLow/Sox15Low/CD133High may be a valuable prognostic marker in patients with human lung cancer.

overall_design: Total cellular RNA was extracted from LM and HM20 cells after treatment with or without Wnt3a for 24hours. Human lung cancer A549 cell–derived spheres were transferred back to adhesive tissue culture plates (LM cells). To establish an EMT/metastasis cell model, LM cells were seeded onto Matrigel-coated Boyden chamber membranes. HM20 cells were serially selected for Matrigel invasion 20 times.


title: Molecular control of myeloid suppressors by death pathways

first: Geoffrey

last: Neale

address: 262 Danny Thomas Place

department: Hartwell Center

institute: St Jude Childrens Research Hospital

summary: The goal of this study was to evaluate the mechanisms distinguishing the different forms of myeloid suppressors in cancer and inflammation, and their indivdual roles in T cell suppression

sample_organism:
Homo sapiens
Mus musculus

platform_organism:
Homo sapiens
Mus musculus

overall_design: We used microarrays to profile the expression profile of myeloid suppressor cells in mouse and human samples. The starting point is the attached arrays which use different CD11+ or CD14+ selections to crudely separate the myeloid suppressors from other immune cells. The overall study is an initial step towards much higher resolution genetics studies to determine the functional prathways used by myeloid suppressors to inhibit T-cells.

first: Jessica

last: Haverkamp

first: Peter

last: Murray


title: Gene expression data from uninfected and rhinovirus-infected peripheral blood mononuclear cells from 98 individuals

status: Public on Apr 14 2015

city: Philadelphia

first: Minal

last: Caliskan

state: PA

address: 415 Curie Blvd., Room 540

department: Genetics

institute: University of Pennsylvania

summary: Rhinovirus (RV) is the most prevalent human respiratory virus. Each year, RV infects billions of people and is responsible for at least half of all common colds, the most common illness of humans. RV infection also affects the morbidity of a range of respiratory illnesses, such as bronchiolitis, pneumonia, asthma, chronic obstructive pulmonary disease, and cystic fibrosis. Despite its biological importance and public health significance, little is known about the genetic architecture of response to RV. To address this, we obtained genome-wide genotype and gene expression data in uninfected and RV-infected peripheral blood mononuclear cells (PBMCs) from 98 individuals. We characterized gene expression differences in response to RV infection and mapped expression quantitative trait loci (eQTLs) in both uninfected and RV-infected PBMCs.

overall_design: The study includes data from uninfected and rhinovirus-infected peripheral blood mononuclear cells (PBMCs) from 98 individuals. Twenty ml of blood was drawn from each participant. PBMCs were isolated from whole blood samples by Ficoll-Paque separation. From each subject, 4 million PBMCs were treated with media alone for 24 hours and 4 million PBMCs were treated with media containing RV16 for 24 hours. The multiplicity of infection was 10 plaque-forming units per cell. Total RNA was extracted after 24-hour incubation, using the RNeasy Plus Mini Kit; concentrations were measured on a Nanodrop ND-100 Spectrophotometer and quality was assessed using an Agilent 2100 Bioanalyzer. Genome wide gene expression profiling of uninfected and rhinovirus-infected PBMCs was obtained using Illumina HumanHT-12 v4 Expression BeadChip arrays at the University of Chicago Functional Genomics Core.

first: Samuel

last: Baker

first: Yoav

last: Gilad

first: Carole

last: Ober


title: Genes differentailly expressed in organ-specific metastatic cells derived from MDA-MB-231 breast cancer cell line

status: Public on Apr 01 2015

city: PHILADELPHIA

first: Chirayu

middle: Pankaj

last: Goswami

address: 110 S 11TH STREET

department: MOLECULAR DIAGNOSTIC LABORATORY

institute: THOMAS JEFFERSON UNIVERSITY HOSPITAL

summary: Breast cancer metastasizes to bone, visceral organs, and/or brain depending on the subtypes. Various cell line models have been used to develop gene expression signatures unique to cancer cells that have metastasized to specific organs, although these efforts were not in a uniform setting. In this study, we compared gene expression pattern in MDA-MB-231 cells and its mammary fat pad tumor (TMD-231), lung metastasis (LMD-231), bone metastasis (BMD-231), adrenal metastasis (ADMD-231) and brain metastasis (231-BR) variants grown under the same growth condition. When gene expression differences between metasteses (p value of <0.01) were compared, 231-BR cells showed the highest gene expression difference (633 genes) followed by ADMD-231 (196 genes), LMD-231 (79 genes), and BMD-231 cells (60 genes) compared with other metastatic cells. 231-BR cells specifically overexpressed neuronal transmembrane proteins SLITRK2, TMEM47, and LYPD1 by more than five fold compared with cells isolated from other sites of metastasis. Ingenuity pathway analysis of differentially expressed genes revealed activation of pathways that would enable cancer cells to adapt to organs of metastasis such as drug detoxification/oxidative stress response/semaphorin neuronal pathway in 231-BR cells, Notch/orphan nuclear receptor signals involved in steroidogenesis in ADMD-231, acute phase response in LMD-231, and cytokine/hematopoietic stem cell signaling in BMD-231 cells. Only NF-κB signaling pathway activation was common to all metastatic cells except BMD-231.To test this possibility, we compared gene expression pattern in MDA-MB-231 cells and its mammary fat pad tumor (TMD-231), lung-metastasis (LMD-231), bone-metastasis (BMD-231), adrenal-metastasis (ADMD-231) and brain-metastasis (231-BR) variants. Between metastatic cells, 231-BR cells showed the highest gene expression difference followed by ADMD-231, LMD-231, and BMD-231 cells. 231-BR cells specifically overexpressed neuronal transmembrane proteins SLITRK2, TMEM47, and LYPD1. pathways that would enable cancer cells to adapt to organs of metastasis such as drug detoxification/oxidative stress response/semaphorin neuronal pathway in 231-BR cells, Notch/orphan nuclear receptor signals involved in steroidogenesis in ADMD-231, acute phase response in LMD-231, and cytokine/hematopoietic stem cell signaling in BMD-231 cells. Only NF-κB signaling pathway activation was common to all metastatic cells except BMD-231.

overall_design: Cells were maintained in MEM with 10% fetal calf serum. RNA was prepared exponentially growing cells using RNeasy kit (Qiagen, Valencia, CA, USA) Microarray with biological triplicates was performed using Illumina HumanHT-12 V4 expression beadchip. Probe profile data was imported into partek genomics suite. Genes that showed statistically insignificant signals in majority of samples were removed from the microarray data, and only those probes that showed statistically significant signal in at least half of samples of at least one group were retained. Differential expression analysis was performed using ANOVA.

first: Harikrishna

last: Nakshatri


title: The effect of miRNA-135b overexpression on the gene expression profile of LNCaP cells

status: Public on Apr 21 2015

city: HELSINKI

first: Anna

last: Aakula

address: Tukholmankatu 8

country: Finland

institute: Institute for Molecular Medicine Finland, FIMM

summary: MicroRNAs (miRNAs) regulate a wide range of cellular signaling pathways and biological processes in both physiological and pathological states such as cancer. We have previously identified miR-135b as a direct regulator of androgen receptor (AR) protein level in prostate cancer (PCa). We wanted to further explore the relationship of miR-135b to hormonal receptors, particularly estrogen receptor α (ERα). Here we show that miR-135b expression inversely correlates with ER protein in two independent breast cancer (BCa) patient cohorts (101 and 1302 samples) and with AR protein in 47 PCa patient samples. We identify ERα as a novel miR-135b target by demonstrating miR-135b binding to the 3’UTR of the ERα and decreased ERα protein and mRNA level in breast cancer cells upon miR-135b overexpression. miR-135b inhibits proliferation of hormone receptor positive cancer cell lines as shown by overexpression in ERα-positive BCa cells (MCF-7) and AR-positive PCa cells (LNCaP, 22Rv1) when grown in 2D. To identify other genes regulated by miR-135b we performed gene expression studies and found a potential link to the hypoxia-inducible factor-1α (HIF1α) pathway. We show that miR-135b influences the protein level of the inhibitor for hypoxia-inducible factor-1 (HIF1AN), which also demonstrated an inverse correlation with miR-135b in a cohort of breast tumor samples. Taken together, our study demonstrates that miR-135b regulates ERα, AR and HIF1AN protein levels and proliferation in ERα -positive breast and AR-positive-prostate cancer cells.

overall_design: LNCaP cells were transfected with Ambion pre-miR™ construct for miR-135b or with pre-miR negative control #1 (scrambled pre-miR, Scr) at 20 nM, and incubated for 12h, 24h or 36h, in two biological repeats (B1 and B2)

first: Suvi-Katri

last: Leivonen

first: Petteri

last: Hintsanen

first: Tero

last: Aittokallio

first: Yvonne

last: Ceder

first: Anne-Lise

last: Børresen-Dale

first: Merja

last: Perälä

first: Päivi

last: Östling

first: Olli

last: Kallioniemi


title: Gene expression profiling of the human natural killer cell response to FcR activation in the presence of IL-12

city: Columbus

first: Kelly

last: Regan

state: Ohio

address: 1800 Cannon Drive

department: Biomedical Informatics

institute: The Ohio State Univ

summary: The majority of NK cells (~90%) are phenotypically characterized as CD56dimCD16+, while the remaining are CD56brightCD16-. The cytotoxic CD56dimCD16+ NK subset expresses higher levels of chemokine receptors, and therefore is preferentially recruited to sites of inflammation. Encounters between CD56dimCD16+ NK cells with target cells and locally secreted inflammatory cytokines synergize to induce activation of this subset, leading to dramatically increased cytotoxic activity against target cells and abundant pro-inflammatory cytokine production often equivalent to that of the CD56brightCD16- population. The early recruitment of activation of CD56dimCD16+ NK cells to sites of inflammation raises many important questions regarding the potential immune functions of these cells that extend beyond their cytotoxic capabilities. This study has sought to elucidate the genetic profile of activated CD56dimCD16+ NK cells via a series of laboratory-based approaches coupled with a bioinformatics persective.

overall_design: We assessed global patterns of gene expression in CD56dimCD16+ human NK cells following FcR stimulation in the presence or absence of the potent immune-stimulatory cytokine, IL-12, as compared to non-stimulated (medium) control samples.

first: Neela

last: Bhave

first: Amanda

last: Harper

first: Robin

last: Parihar

first: Philip

middle: R

last: Payne

first: William

last: Carson III


title: Pathways for intervention to optimize donor organ quality uncovered: a genome wide gene expression study

city: Groningen

first: Jeffrey

last: Damman

address: Hanzeplein 1

country: Netherlands

institute: University Medical Center Groningen

summary:
Background: Strategies to improve long term renal allograft survival have been directed to recipient dependent mechanisms of renal allograft injury. In contrast, no such efforts have been made to optimize organ quality in the donor. In order to get insight into the deleterious gene pathways expressed at different time points during deceased kidney transplantation, transcriptomics was performed on kidney biopsies from a large cohort of deceased kidney transplants.
Methods: A total of 554 kidney biopsies were taken from living and deceased donor kidneys at donation, after cold ischemia and after reperfusion. Transcriptomics by means of whole genome micro-array analyses followed by functional pathway analyses was performed.
Results: Oxidative stress and complement- and coagulation pathways were uncovered as potential pathways for intervention in deceased donors.  No genes were found to be differentially expressed between donation and cold ischemia. After reperfusion, pathways related to oxidative stress, NOD-like signalling, MAPK, cytokine-cytokine receptor, complement- and-coagulation and chemokines were enriched in kidneys from deceased organ donors. Pathways related to prolonged and worsening deprivation of oxygen were associated with delayed graft function of DCD grafts.
Conclusions: The present study reveals oxidative stress and enrichment of complement and coagulation pathways in deceased donor kidneys. Future intervention therapies to optimize donor organ quality and prolong allograft survival should target oxidative stress and innate immune activation in the donor.

overall_design:
Total RNA was isolated from kidney biopsies. Biopsies were taken from deceased brain-dead kidney donors (n=81) and deceased cardiac dead donors (n=37) before organ retrieval.  From another transplant cohort, kidney biopsies were taken after cold ischemia and after reperfusion of a brain-dead donor kidney (n=67 paired, 43-38 unpaired) or cardiac-dead donor kidney (n=29 paired, 24-35 unpaired).  Living donors kidney biopsies (n=37) and paired living reperfusion biopsies (n=34) served as controls.
Three timepoints:
T1 = Kidney biopsy taken before organ retrieval in deceased donors
T2 = After cold ischemia
T3 = 60 minutes after reperfusion

first: Marc

last: Seelen


title: Effect of MEG3 on p53 target genes in hepatoma cells

status: Public on Jun 17 2015

city: Beijing

first: Juanjuan

last: Zhu

address: 27 Taiping Road

institute: Beijing Institute of Radiation Medicine

summary: Maternally Expressed Gene 3 (MEG3) encodes a lncRNA which is suggested to function as a tumor suppressor. MEG3 functions as a tumor suppressor in hepatoma cells, whose action is mediated by interaction with p53 protein to activate p53-mediated transcriptional activity and influence the expression of partial p53 target genes.

overall_design: Total RNA was isolated from hepatoma cells (HepG2 and SK-Hep-1) transfected with either control or MEG3 overexpression/knockdown constructs for global expression analysis.

first: Xiaofei

last: Zheng


title: Tumor-educated circulating monocytes are powerful specific biomarkers for diagnosis of colorectal cancer

city: Leuven

first: Rekin's

last: Janky

address: Herestraat 49 Box 816

department: Nucleomics Core

country: Belgium

institute: VIB

summary: Analysis of tumor-educated changes in peripheral blood monocytes at the gene expression level. We analyzed if gene expression in monocytes of patients with colorectal cancer is differential from those of healthy volunteers and found a diagnostic signature that allowed to accurately discriminate patients with colorectal cancer from healthy individuals.

overall_design: Peripheral blood monocytes from 93 distinct individuals are profiled on 8 beadchips. The individuals belong to one of three groups: healthy volunteers (38), patients with non-metastatic colorectal cancer (27) or patients with metastatic colorectal cancer (28).

first: Alexander

last: Hamm

first: Hans

last: Prenen

first: Mathias

last: Wenes

first: Estelle

last: Delamarre

first: Wouter

last: Van Delm

first: Thomas

last: Schmidt

first: Jürgen

last: Weitz

first: Roberta

last: Sarmiento

first: Angelo

last: Dezzi

first: Giampietro

last: Gasparini

first: Françoise

last: Rothé

first: Alain

last: Hendlisz

first: André

last: D’Hoore

first: Hannes

last: Iserentant

first: Martin

last: Pejcinovski

last: Schmitz

first: Massimiliano

last: Mazzone


title: Gene expression in patient and control T cells

status: Public on Jun 01 2015

city: London

first: Paul

last: Lavender

address: 5th Floor, Tower Wing, Great Maze Pond

department: School of Immunology and Microbial Sciences

institute: King's College London

summary:
anti-CD3 + anti-CD46 stimulation for 2hr
Patient has a mutation in CD46 that leads to reduced cell surface CD46 expression and suffers from episodes of atypical hemolytic uremic syndrome (aHUS), common variable immune deficiency (CVID) and recurrent infections

overall_design: total RNA isolated from CD4+ T cells

first: Claudia

last: Kemper


title: G9a target gene screening: H3K9 methyltransferase G9a negatively regulates UHRF1 transcription during leukemia cell differentiation

city: Seoul

first: Kee-Beom

last: Kim

address: Heusokdong

country: South Korea

institute: Chung-Ang University

summary: A genome-wide analysis identified a subset of G9a target genes including UHRF1

overall_design: Total RNA obtained from isolated G9a knockdown stable cell in K562 cells compared to sh-CTL control stable cells.

first: Hye-Ju

last: Son

first: Sang-Beom

last: Seo


title: Effect of MK591 on gene expression in LNCaP cells

status: Public on Mar 31 2015

city: Detroit

first: Jagadananda

last: Ghosh

state: MI

address: 1 Ford Place

department: Urology

institute: Henry Ford Health System

summary: Cells were treated with MK591 and gene expression was analyzed with Illumina bead chip array.

overall_design: LNCaP cells were plated and allowed to grow for 48 hours. Then the cells were treated with MK591, total RNA isolated, and analyzed by Illumina HT-12v4 gene expression array.


title: Gene expression profiles of PTPRZ1-knocking-down human glioblastoma stem cells [PrimeView]

status: Public on May 21 2015

city: Chongqing

first: Yu

last: Shi

state: Chongqing

address: Gao-tan Yan Street

department: Southwest Hospital

institute: Institute of Pathology and Southwest Cancer Center

summary: Glioblastoma stem cells (GSCs), are at the apex of its cellular hierarchy and contribute to glioblastoma progression and tumor recurrence. Gene expression profiling is useful in determining the genome-wide gene expression changes based on the experimental purpose. In order to interrogate the downstream targets of PTPRZ1, we applied gene expression profiling approach to screen the altered genes that are responsible for the functional phenotype changes. The results will provide a cue for mechanical analysis with potential translational values.

overall_design: PTPRZ1-knocking down glioblastoma stem cells (GSCs) and control GSCs were used in this study. RNA were isolated using  Primescript RT Master Mix (Takara). Profiling was established by applying PrimeView Affymetrix Human Gene Expression Array.

first: Yi-fang

last: Ping


title: Effects of differentiated hMADS adipocytes on BT474 and SKBR3 breast cancer cells

city: Lyon

first: Minh Ngoc

last: Duong

address: 28 rue Laennec

department: Immunity, Microenvironment and Virus

country: France

institute: INSERM U1052 - CNRS 5286

summary: Analysis of gene expression levels of HER2-positive breast cancer cells exposed to the conditioned medium from adipocytes. The hypothesis tested in the present study was that adipocytes secrete factors that induce the resistance of cancer cells to antibody-dependent cellular cytotoxicity mediated by trastuzumab. The results provide insight into the genes that may be involved in the adipocyte-induced cancer resistance to trastuzumab treatment.

overall_design: BT474 cells or SKBR3 cells were exposed to the conditioned medium (CM) from differentiated hMADS (#hMADS) or to the control medium for 2 h. Total RNA was extracted and analyzed. The experiment was performed in triplicate.

first: Minh

middle: N

first: Aurore

last: Cleret

first: Kamel

last: Chettab

first: Delphine

last: Demangel

first: Charles

last: Dumontet


title: Transcriptome analysis of HIV-infected peripheral blood monocytes

city: Los Angeles

first: Steve

last: Horvath

state: CA

address: 695 Charles E. Young Drive South, Box 708822

department: Human Genetics

institute: University of California, Los Angeles

summary: Immunologic dysfunction, mediated via monocyte activity, has been implicated in the development of HIV-associated neurocognitive disorder (HAND). We hypothesized that transcriptome changes in peripheral blood monocytes relate to neurocognitive functioning in HIV+ individuals, and that such alterations could be useful as biomarkers of worsening HAND. METHODS:  mRNA was isolated from the monocytes of 86 HIV+ adults and analyzed with the Illumina HT-12 v4 Expression BeadChip. Neurocognitive functioning, HAND diagnosis, and other clinical and virologic variables were determined.

first: Andrew

last: Levine


title: Analysis of global gene expression profiles of A549 cells treated with Xrn2 siRNA upon Influenza A/PR/8/34(ΔNS1) Infection

status: Public on Mar 30 2015

first: Ivan

last: Marazzi

address: 1468 Madison Avenue

department: Department of Microbiology

institute: Icahn School of Medicine at Mount Sinai

summary: Untransfected (no siRNA), control siRNA or Xrn2 siRNA treated A549 cells were infected with A/Puerto Rico/8/1934(ΔNS1) for 4 hours

overall_design: 3 Biological Replicates per condition

first: Matthew

last: Miller

first: Alexander

last: Rialdi

first: Jessica

last: Ho

first: Micah

last: Tilove

first: Luis

last: Martinez-Gil

first: Natasha

middle: P

last: Moshkina

first: Zuleyma

last: Peralta

first: Justine

last: Noel

first: Camilla

last: Melegari

first: Ana

last: Maestre

first: Panagiotis

last: Mitsopoulos

first: Joaquín

last: Madrenas

first: Sven

last: Heinz

first: Chris

last: Benner

first: John

last: Young

first: Alicia

last: Feagins

first: Christopher

last: Basler

last: Fernandez-Sesma

first: Olivier

last: Bequerel

first: Martin

last: Lavin

first: Harm

last: van Bakel


title: Analysis of global gene expression profiles of A549 cells treated with XRN2 siRNA under basal conditions

first: Ivan

last: Marazzi

summary: Untransfected (no siRNA), control siRNA or XRN2 siRNA treated A549 cells were analyzed for gene expression differences under basal conditions

first: Matthew

last: Miller

first: Alexander

last: Rialdi

first: Jessica

last: Ho

first: Micah

last: Tilove

last: Martinez-Gil


title: Analysis of global gene expression profiles of A549 cells treated with SETX siRNA upon Influenza A/PR/8/34(ΔNS1) Infection

summary: Untransfected (no siRNA), control siRNA or SETX siRNA treated A549 cells were infected with A/Puerto Rico/8/1934(ΔNS1) for 4 hours

first: Luis

first: Natasha

last: Moshkina

first: Zuleyma

last: Peralta

first: Justine

last: Noel

first: Camilla

last: Melegari

last: Maestre

last: Mitsopoulos


title: Robust enumeration of cell subsets from tissue expression profiles (HGU133A)

status: Public on Mar 29 2015

city: Stanford

first: Aaron

last: Newman

address: 265 Campus Drive

department: Institute for Stem Cell Biology and Regenerative Medicine & Division of Oncology, Stanford School of Medicine

institute: Stanford University

summary: We introduce CIBERSORT, a method for characterizing cell composition of complex tissues from their gene expression profiles. When applied to enumeration of hematopoietic subsets in RNA mixtures from fresh, frozen, and fixed tissues, including solid tumors, CIBERSORT outperformed other methods with respect to noise, unknown mixture content, and closely related cell types. CIBERSORT should enable large-scale analysis of RNA specimens for cellular biomarkers and therapeutic targets (http://cibersort.stanford.edu).

overall_design: To evaluate the performance of CIBERSORT for enumerating Tregs, RNA was extracted from PBMC samples from 6 healthy normal controls and 1 follicular lymphoma (FL) patient. All PBMC samples were also interrogated by flow cytometry for FOXP3+ Tregs.

first: Chih-Long

last: Liu

first: Michael

last: Green

first: Andrew

last: Gentles

first: Weiguo

last: Feng

first: Yue

last: Xu

first: Chuong

last: Hoang

first: Maximilian

last: Diehn

first: Ash

last: Alizadeh


title: IL-17A and IL-6 -stimulated expression data from primary epithelial cell cultures derived from human trachea tissues

status: Public on Mar 28 2015

city: Davis

first: Reen

last: Wu

state: CALIFORNIA

address: 451 Health Sciences Dr.

department: Center for Comparative Respiratory Biology and Medicine

institute: University of California Davis

summary:
RNAs were isolated from primary cultures after 24 hour treatment with IL-17A or IL-6 (10 ng/ml) in primary human TBE cells.
We used microarrays to analyze the global gene expression profiling of IL-17A or IL-6 regulated genes in TBE cells.

overall_design: TBE cells were grown and stimutaed with the cytokines indicated. Total RNA were then extracted for Affymetrix microarray studies.

first: Yin

last: Chen

first: Shinichiro

last: Wachi


title: Generation of Integration-free Induced Neural Stem Cells from Mouse Fibroblasts

status: Public on Mar 27 2015

first: sung min

last: kim

address: neudong ro 120

institute: Konkuk university

summary:
Recent studies demonstrated that fibroblasts could be converted into induced neural stem cells (iNSCs). However, the insertional mutation caused by random integration of viral vectors has been a major limitation of iNSCs for the future clinical translation. Here we show that non-viral transfection of episomal vectors encoding Brn4/Pou3f4, Sox2, Klf4, and c-Myc sufficiently generates iNSCs.
The episomal vector mediated iNSCs closely resemble brain-derived NSCs as well as iNSCs generated by retrovirus in morphology, gene expression profile, epigenetic status, self-renewal capacity and both in vitro and in vivo differentiation capacity. The novel conversion protocol defined in the current study offers a method for generating integration-free iNSCs for the clinical research

overall_design: we developed a novel method for generating integration-free iNSCs. We demonstrated that oriP/EBNA1-based episomal vectors could generate iNSCs by single transfection

first: Sung-Min

last: Kim

first: Dong-Wook

last: Han


title: Genome-wide analysis of basal gene expression analysis of pediatric acute lymphoblastic leukaemia xenograft cells

city: Randwick

first: Duohui

last: Jing

state: NSW

address: Lowy Cancer Research Centre, UNSW

department: Leukaemia Biology

country: Australia

institute: Children’s Cancer Institute Australia

summary: Analysis of patient-derived xenograft cells at the basal level. A panel of T- and BCP-ALL pediatric leukaemia xenograft cells were utilised to further understand the biology of pediatric leukaemia.

overall_design: Total RNA were isolated from patient-derived xenograft cells. Illumina beadchip HT12 were utilised

first: Richard

last: Lock

first: Hernan

last: Carol

first: Santi

last: Suryani

first: Laura

last: High


title: microRNA Induction of Fatal Differentiation Programs is a Context-selective Vulnerability in Ovarian Cancer Cells [PEO4]

city: Dallas

first: Michael

last: White

address: 6000 Harry Hines Blvd.

department: Cell Biology

institute: University of Texas Southwestern Medical Center

summary: Analysis of gene expression in ovarian cancer cells with and without overexpression of the miRNA mir-124 which will provide data about genes possibly directly regulated by miR-124.  Also, analysis of gene expression in ovarian cancer cells with and without knockdown of the homeodomain transcription factor SIX4 (a target of miR-124) which will provide data about genes possibly directly regulated by SIX4

overall_design: Total RNA was isolated from PEO4 cells transfected with miRNA mimic negative control (miNC), miR-124 mimic, siRNA negative control (siNC) oligo, or siRNA targeting the SIX4 gene (siSIX4) 72 hours post-transfection

first: Benjamin

last: Shields


title: microRNA Induction of Fatal Differentiation Programs is a Context-selective Vulnerability in Ovarian Cancer Cells [PEO1]

overall_design: Total RNA was isolated from PEO1 cells transfected with miRNA mimic negative control (miNC), miR-124 mimic, siRNA negative control (siNC) oligo, or siRNA targeting the SIX4 gene (siSIX4) 72 hours post-transfection


title: The effect of Sendai virus infection using 2 concentrations on U937 cells

status: Public on Mar 25 2015

city: Bethesda

first: Luna

last: Zaritsky

state: MD

address: 50 South Drive

institute: NIH

summary: Sendai virus is a potent inducer of type I interferons in human cells. Type I interferons consist of 13 different IFN alpha genes and 1 IFN beta gene. Each of these subtypes have differing functional activites depending on the infecting virus and cell. However, the exact signaling pathways that lead to the induction of individual type I IFN subtypes are not known. We have found that inefction with 2 different concentrations of Sendai virus in the human monocytoid cell line U937 results in 2 distinct profiles of type I IFN subtypes. In other words, inefction with a high concentration of virus results in the induction of a certain subset of subtypes,  while infection with a lower concetration results in the induction of a different subset of subtypes  We therefore wanted to determine which signaling pathways were activated during infection with these 2 different virus concentrations in order to see which signaling pathways may be involved in the induction of individual type I IFN subtypes. We also wanted to determine if the existence of different type I IFN subtype profiles resulted in different profiles of interferon stimulated genes. We therefore performed microarray analysis on U937 cells that were uninfected or infected with either 150 or 1.5 HA units/mL of SeV for 24 hours.

overall_design: U937 cells were uninfected or infected with either 1.5 or 150 HA u/mL of SeV (corresponding to MOIs of 0.0002 and 0.02, respectively) for 24 h. RNA was isolated and microarray was performed.


title: Modular expression analysis reveals functional conservation between human Langerhans Cells and mouse cross-priming dendritic cells

first: Maxim

middle: N.

last: Artyomov

state: MO

address: 660 S. Euclid Avenue, Campus Box 8118

department: Immunology&Pathology

institute: Washington University in St.Louis

summary: Characterization of functionally distinct Dendritic Cell (DC) subsets in mice has fueled interest in whether analogous counterparts exist in humans. Transcriptional modules of coordinately expressed genes were utilized for defining shared functions between the species. Comparing modules derived for four human skin DC subsets, and modules derived from the Immunological Genome Project database for all mouse DC subsets, revealed that human Langerhans Cells (LCs) and the mouse XCR1+CD8α+CD103+ DCs shared the Class I-mediated antigen processing and cross-presentation transcriptional modules that, however, were not seen in mouse LCs. Furthermore, human LCs were enriched in a transcriptional signature specific to the blood cross-presenting CD141/BDCA-3+ DCs, the proposed equivalent to mouse CD8α+ DCs. Consistent with our analysis, LCs were highly adept at inducing primary CTL responses. Thus, our study suggests that the function of LCs may not be conserved between mouse and human and supports human LCs as an especially relevant therapeutic target.

overall_design: RNA from sorted populations was purified using TRIzol. RNA was processed, amplified, labeled and hybridized at Washington University Core Facility (GTAC) with Illumina HumanHT-12 v4 Expression BeadChip. Data were background subtracted and quantile normalized.


title: Gene expression profile of hESC/hIPC-derived keratinocytes

first: Matthew

last: Arno

state: LONDON

address: 150 Stamford Street

department: Genomics Centre

summary: To induce the differentiation, undifferentiated human pluripotent stem cells (both hESC andh iPSC; T0 time point) were transferred into 20% O2 atmosphere environment and treated with mTESR1 basal media supplemented with 1 μM ATRA (Sigma-Aldrich) and 25 ng/ml BMP4 (R&D) for 7 days (Induction). To select for the cells that acquired early ectodermal fate, cells were harvested and re-plated onto freshly prepared 3D human dermal fibroblast ECM at a density of 5-10x10^3 cells per cm2 and grown in DMEM:Ham F12 (3:1) (Life Technologies) supplemented with 1 μM ATRA and 25 ng/ml BMP4 for a further 7 days (Selection). To enrich for putative epidermal progenitors, rapid-adhesion to type IV collagen-coated dishes was used, and the rapidly-adhering cells were cultured in DK SFM supplemented with 1 μM ATRA for 7 days (Enrichment). After that, the cells were cultured in EpiLife medium (Life Technologies) for a further 7 days (Expansion) before final harvest (T3 time point) and analysis. We analyzed here gene expression profiles of undifferentiated hESC/hiPSC (T0), hESC/hIPC-derived keratinocytes (T3) and primary normal human keratinocytes from skin biopsy (NHK). We found that hESC/hIPC-derived keratinocytes are similar to NHK.

overall_design: Biological triplicates of undifferentiated (T0) hESC (KCL034) and hiPSC lines (iKCL004, iKCL011) were compared with hESC/hiPSC-derived keratinocytes (T3), primary human keratinocyes (NHK) and fibroblasts (BJ).

first: Anastasia

last: Petrova

first: Dusko

last: Ilic


title: Disrupted functional neworks in autism underlie early brain maldevelopment and provide accurate classification

status: Public on Mar 24 2015

city: San Diego

first: Tiziano

last: Pramparo

address: 3611 Valley Centre Drive

department: R&D

institute: Travere

summary:
The disrupted genetic mechanisms underlying neural abnormalities in Autism Spectrum Disorder remain mostly unknown and speculative. No biological marker nor genetic signature is currently available to assist with early diagnosis.
We identified a blood-based gene expression signature relevant to the brain pathophysiology in autism. Also we identified genes that are differentially expressed in ASD subjects vs controls and gene modules that efficiently classify ASD and TD subjects.

overall_design: Leukocyte gene expression levels were analysed in autistic and tipically develoing infants and toddlers with the purpose to identify gene expression signatures relevant to the autistic brain and to assist in the classification of subjects.

first: Eric

last: Courchesne


title: Immortalization of T-cells is accompanied by gradual changes in CpG methylation resulting in a profile resembling a subset of T-cell leukemias [expression]

city: Umeå

first: Sofie

last: Degerman

state: Sweden

address: NUS, Blg 6M, 2nd floor

department: Medical Biosciensces

country: Sweden

institute: Umeå University

summary: We have previously described gene expression changes during spontaneous immortalization of T cells, thereby identifying cellular processes important for cell growth crisis escape and long term proliferation. Here we analyze the same model to investigate the role of genome-wide methylation in the immortalization process at different time points pre- and post- crisis using high-resolution arrays. We show that over time in culture there is an overall accumulation of methylation alterations, with  preferential increased methylation close to transcription start sites, island and shore regions. Most methylation alterations did not affect gene expression but among the affected genes, increased methylation close to transcription start site was associated with decreased gene expression.   Interestingly, the pattern of CpG site methylation observed in post-crisis T-cell cultures was similar to clinical T-cell acute lymphoblastic leukemia (T-ALL) samples classified as CpG island methylator phenotype positive (CIMP+). These sites were highly overrepresented by polycomb target genes and involved in developmental, cell adhesion and cell signaling processes. The presence of nonrandom methylation events in in vitro immortalized T-cell cultures and diagnostic T-ALL samples indicates altered methylation of CpG sites with a possible role in malignant hematopoiesis.

overall_design:
RNA was extracted with TRIZOL according to manufacturer instructions. Total RNA was amplified bu the Illumina TotalPrep RNA Amplification kit.
Gene expression array analysis was performed on the cell cultures.

first: Mattias

last: Landfors

first: Jan

middle: K

last: Siwicki

first: John

last: Revie

first: Magnus

last: Borssén

first: Emma

last: Evelönn

first: Erik

last: Forestier

first: Krystyna

last: Chrzanowska

first: Patrik

last: Rydén

first: W

last: Keith

first: Göran

last: Roos


title: Generation of integration-free induced hepatocytes from mouse fibroblasts

city: seoul

first: Jonghun

last: Kim

address: 120 neungdong-ro, Gwangjin-gu

department: school of medicine

institute: Konkuk univ.

summary:
Previous studies demonstrated that hepatocyte-specific transcription factors could directly convert fibroblasts into functional hepatocytes-like cells, namely induced hepatocytes (iHeps) using viral systems. However, viral integration into host genome causes insertional mutation and risk of tumorigenecity.
we showed iHeps could be generated from MEFs using the integration-free system. They were expandable in vitro and showed hepatic features, similar to primary hepatocytes.

overall_design: iHeps_G4H1F3 transfected (Episomal vectors) and iHeps_G4H1F3 transduced (pMXs) were duplicate, respectively. MEFs and primary hepatocytes were used as negative and positive controls, respectively.

first: Kee-Pyo

first: Dong

last: Han


title: Expression data from regenerating mouse TA muscle

status: Public on Mar 19 2015

city: Charlotte

first: Qi Long

last: Lu

state: North Carolina

address: 1000 Blythe Blvd

department: Neurology

institute: Carolinas HealthCare System

summary:
Mutations in fukutin-related protein (FKRP) gene are characterized with a lack of functionally glycosylated α-dystroglycan (F-α-DG). Surprisingly a small number of muscle fibers express strong F-α-DG. Here we investigate restoration of F-α-DG in FKRP mutant muscle and showed that the restoration of glycosylation is associated with muscle regeneration and dependent of the expression of both LARGE and partially functional FKRP. F-α-DG in regenerating fibers reaches normal levels and lasts for more than 4 weeks, however, no up-regulation of the LARGE and FKRP is detected during the regeneration process. These results suggest that FKRP P448L mutation clinically associated with severe CMD retains at least partial functions. Identification of factor(s) other than LARGE and FKRP could create new approaches for restoration of F-α-DG in mature muscle fibers with defects in FKRP function.
We employed microarrays to detail changes in gene expression associated with muscle regeneration in wild-type and FKRP mutant skeletal muscle, and have identified a group of genes with altered expression between these mice during this regeneration process.

overall_design: RNA from TA muscles of untreated control and i.m. NTX treated FKRP (P448L) mutant mice were compared by microarray at 2, 4, and 14 days post treatment to assess regenerative effects on gene expression.

first: Qi

middle: L

first: Hiroyuki

last: Awano

first: Jason

middle: D

last: Tucker


title: Analysis of global gene expression profiles of A549 cells treated with SETX siRNA under basal conditions

city: New York

first: Ivan

last: Marazzi

summary: Untransfected (no siRNA), control siRNA or SETX siRNA treated A549 cells were analyzed for gene expression differences under basal conditions

first: Matthew

middle: S

last: Miller

first: Alexander

last: Rialdi

first: Jessica

last: Ho

first: Micah

last: Tilove

first: Luis

last: Martinez-Gil

first: Natasha

last: Moshkina

first: Zuleyma

last: Peralta

first: Justine

last: Noel

first: Camilla

last: Melegari

first: Ana

last: Maestre

first: Panagiotis

last: Mitsopoulos

first: Joaquín

last: Madrenas

first: Sven

last: Heinz

first: Chris

last: Benner

last: Young

first: Alicia

last: Feagins

first: Christopher

last: Basler

last: Fernandez-Sesma

first: Olivier

last: Bequerel

first: Martin

last: Lavin

first: Harm

last: van Bakel


title: Expression data from human colonic cancer cell line SW480 and its acquired 17-AAG resistance cell line SW480-R

status: Public on Mar 14 2015

city: Kunming

first: youguang

last: huang

state: Yunnan Province

address: 519 Kunzhou Road

department: Tumor Institute of Yunnan Province

institute: The Third Affiliated Hospital of Kunming Medical University

summary:
Heat shock protein 90 (HSP90) is a molecular chaperone required for the stability and function of many proteins. The chaperoning of oncoproteins by HSP90 enhances survival, growth and invasive potential of cancer cells. HSP90 inhibitors are promising new anticancer agents, in which the benzoquinone ansamycin 17-allylamino-17-demethoxygeldanamycin (17-AAG) is currently in clinical evaluation. However, the implications of acquired resistance to this class of drug remain largely unexplored. In the present study, we have generated isogenic human colonic cancer cell line SW480 that is resistant to 17-AAG by continued culturing in the compound.
We used microarrays to detail the global programme of gene expression underlying the acquired resistance to 17-AAG in SW480 and SW480-R cell lines.

overall_design: SW480 cells were incubated and treated with 17-AAG at an initial concentration of 1×IC50. The medium with the compound was replaced every 48 h to discard dead cells. When surviving cells grow to 80% confluence, cells were passaged and the 17-AAG concentration was then added as follows: 2×, 4×, 6× ……IC50 till undulated. The generated resistant cell line(SW480-R) was cultured without 17-AAG at least of 2 weeks for RNA extraction and hybridization on Affymetrix microarrays, and for other analysis. Paired parental cells in another flask were serially passaged without 17-AAG as an untreated control.

first: Xin

last: Liu

first: You-guang

last: Huang


title: Novel HDAC inhibitors exhibit pre-clinical efficacy in lymphoma models and point to the importance of CDKN1A expression levels in mediating their anti-tumor response

status: Public on Mar 18 2015

city: Bellinzona

first: Francesco

last: Bertoni

state: Ticino

address: Via V. Vela 6

department: Lymphoma & Genomics Research Program

country: Switzerland

institute: IOR

summary: investigate the pre-clinical activities of two novel histone deacetylase inhibitors (HDACi), ITF-A and ITF-B, in a large panel of pre-clinical lymphoma models

overall_design: GEP analysis of 2 lymphoma cell lines with and without treatment

first: Afua

middle: A

last: Mensah

first: Ivo

last: Kwee

first: Eugenio

last: Gaudio

first: Andrea

last: Rinaldi


title: Human basophil expression profiles

status: Public on Mar 20 2015

city: Baltimore

first: Donald

middle: Welton

last: MacGlashan

address: 5501 Hopkins Bayview Circle

department: Allergy and Clinical Immunology

institute: Johns Hopkins University

summary: This SuperSeries is composed of the SubSeries listed below.

overall_design: Refer to individual Series


title: Progesterone receptor-B enhances estrogen responsiveness of breast cancer cells via scaffolding PELP1- and estrogen receptor-containing transcription complexes

status: Public on Mar 15 2015

city: Minneapolis

first: Todd

last: Knutson

state: MN

address: 117 Pleasant St SE

department: Minnesota Supercomputing Institute

institute: University of Minnesota

summary: Progesterone and estrogen are important drivers of breast cancer proliferation. Herein, we probed estrogen receptor-α (ER) and progesterone receptor (PR) cross-talk in breast cancer models. Stable expression of PR-B in PR-low/ER+ MCF7 cells increased cellular sensitivity to estradiol and insulin-like growth factor 1 (IGF1), as measured in growth assays performed in the absence of exogenous progestin; similar results were obtained in PR-null/ER+ T47D cells stably expressing PR-B. Genome-wide microarray analyses revealed that unliganded PR-B induced robust expression of a subset of estradiol-responsive ER target genes, including cathepsin-D (CTSD). Estradiol-treated MCF7 cells stably expressing PR-B exhibited enhanced ER Ser167 phosphorylation and recruitment of ER, PR and the proline-, glutamate- and leucine-rich protein 1 (PELP1) to an estrogen response element in the CTSD distal promoter; this complex co-immunoprecipitated with IGF1 receptor (IGFR1) in whole-cell lysates. Importantly, ER/PR/PELP1 complexes were also detected in human breast cancer samples. Inhibition of IGF1R or phosphoinositide 3-kinase blocked PR-B-dependent CTSD mRNA upregulation in response to estradiol. Similarly, inhibition of IGF1R or PR significantly reduced ER recruitment to the CTSD promoter. Stable knockdown of endogenous PR or onapristone treatment of multiple unmodified breast cancer cell lines blocked estradiol-mediated CTSD induction, inhibited growth in soft agar and partially restored tamoxifen sensitivity of resistant cells. Further, combination treatment of breast cancer cells with both onapristone and IGF1R tyrosine kinase inhibitor AEW541 was more effective than either agent alone. In summary, unliganded PR-B enhanced proliferative responses to estradiol and IGF1 via scaffolding of ER-α/PELP1/IGF1R-containing complexes. Our data provide a strong rationale for targeting PR in combination with ER and IGF1R in patients with luminal breast cancer.

overall_design: The study contains 4 different sample groups measured in triplicate, for a total of 12 individual samples (12 arrays). From parental MCF7 human breast cancer cell lines, we created two stable clones expressing either (1) an empty vector (pSG5) or (2) the wild type progesterone receptor isoform B (pSG5-PR-B). These two cell lines were treated with either (1) vehicle control (ethanol) or (2) estradiol 10e-7 M (E2) for 6 hours before total RNA harvest. Thus, the experiment contains two cell lines, and two treatments (4 sample groups) treated and analyzed in triplicate (12 microarrays). Standard Illumina HT-12v4 chip controls were used during hybridization.

last: Daniel

first: Carol

last: Lange


title: Genome-wide analysis of human bone marrow CD45-CD271+ cells in comparision with CD45-CD271- cells

status: Public on Mar 17 2015

city: Lund

first: Hongzhe

last: Li

address: Klinikgatan 26

department: Lund Stem Cell Center

institute: Lund University

summary: Analyze and compare the gene expression profile of human bone marrow primary CD45-CD271+ and CD45-CD271- cells. The hypothesis was some genes were differentially expressed in these two populations. Results provided important information regarding the gene expression difference of these two cell populations.

overall_design: Total RNA obtained from isolated CD45-CD271+ and CD45-CD271- cells were amplified and genome wide gene profiling was compared.


title: Affymetrix PrimeView human gene expression of different cell lines

city: Shanghai

first: YANG

middle: YING

last: CHENG

address: International Co-operation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute, Second Military Medical University

institute: EHBH

summary:
microRNAs are post-transcriptional regulators by degrading the target mRNA. miRNAs can regulate and control a variety of biological processes.
We want to use these Affymetrix PrimeView microarrays to find different genes between negative control cells and miR-484 cells.

overall_design: Total RNA were amplified, labeled and purified by using GeneChip 3'IVT Express Kit (Cat#901229, Affymetrix, Santa Clara, CA, US) followed the manufacturer's instructions to obtain biotin labeled cRNA.Array hybridization and wash was performed using GeneChip® Hybridization, Wash and Stain Kit (Cat#900720, Affymetrix, Santa Clara, CA, US) in Hybridization Oven 645 (Cat#00-0331-220V, Affymetrix, Santa Clara, CA, US) and Fluidics Station 450 (Cat#00-0079, Affymetrix, Santa Clara, CA, US) followed the manufacturer's instructions. Slides were scanned by GeneChip® Scanner 3000 (Cat#00-00212, Affymetrix, Santa Clara, CA, US) and Command Console Software 3.1 (Affymetrix, Santa Clara, CA, US) with default settings. Raw data were normalized by RMA algorithm, Gene Spring Software 11.0 (Agilent technologies, Santa Clara, CA, US).

first: Yingcheng

last: Yang


title: Robust enumeration of cell subsets from tissue expression profiles (BeadChip)

first: Aaron

middle: M

last: Newman

address: 265 Campus Drive

institute: Stanford University

summary: We introduce CIBERSORT, a method for characterizing cell composition of complex tissues from their gene expression profiles. When applied to enumeration of hematopoietic subsets in RNA mixtures from fresh, frozen, and fixed tissues, including solid tumors, CIBERSORT outperformed other methods with respect to noise, unknown mixture content, and closely related cell types. CIBERSORT should enable large-scale analysis of RNA specimens for cellular biomarkers and therapeutic targets (http://cibersort.stanford.edu).

overall_design: To evaluate the performance of CIBERSORT against flow cytometry, gene expression profiling was performed on a set of 20 PBMC samples comprised of adults of varying ages receiving influenza immunization (NCT01827462). These samples were analyzed by flow cytometry to enumerate several leukocyte subsets. Normalized gene expression data and accompanying flow cytometry data are available at the CIBERSORT website (http://cibersort.stanford.edu/download.php).

first: Chih

first: Michael

last: Green

first: Andrew

middle: J

last: Gentles

first: Weiguo

last: Feng

first: Yue

last: Xu

first: Chuong

last: Hoang

first: Maximilian

last: Diehn

first: Ash

last: Alizadeh

first: Holden

last: Maecker

first: Mark

last: Davis


title: Expression data from human primary monocytes

status: Public on Mar 06 2015

city: Muenster

first: Nadine

last: Nippe

address: Roentgenstr. 21

department: Institute of Immunology

country: Germany

institute: University of Muenster

summary:
We analyzed the delayed LPS-induced expression pattern in monocytes.
Activation of monocytes by microbial products is an important mechanism contributing to host protection against invading pathogens. This process has to be tightly controlled to ensure that antimicrobial response does not result in fatal host tissue damage. Therefore we investigated control mechanisms during prolonged monocyte activation by bacterial endotoxin.

overall_design: We performed a genome-wide analysis of lipopolysaccharide (LPS)-triggered expression profile in monocytes after 4 hours and 16 hours. To identify destinct delayed LPS-induced expression pattern  we compared these both expression profiles.

first: Jan

last: Ehrchen


title: Human basophil expression profiles (in vitro) (Ref12)

first: Donald

last: MacGlashan

summary:
Human basophils were examined in vitro for changes in their mRNA expression profiles during stimulation under a variety of conditions. Basophils were obtained from two sources prior to purification, residual cell packs from leukapheresis procedures (which represent the 80% of the sample results) or by venipuncture. For cells obtained by leukapheress, purification included application of elutration, 2-step Percoll gradients and negative selection on Miltenyi columns using StemSep basophil isolation antibodies (see J. Immunol. Methods, 385:51, 2012). For cells obtained by venipuncture, purification included application of 2-step Percoll gradients following by negative selection on Miltenyi columns using StemSep basophil isolation antibodies. The time from subject donation to the start of an in vitro study (first lysis for mRNA) ranged from 6-7 hours for leukapheresis packs to 4-5 hours for venipuncture. Basophil purities averaged 99% for these studies.
For most of the studies, purified basophils were incubated in RPMI-1640 media supplemented with human serum albumin (0.03%), 20 µg/ml gentamycin and glutamine (as glutamax) for several hours to 3 days depending on the stimulus. For most experiments, the day 0 lysis acted as the initial control in order to examine profiles for changes due to simple culture. The study included stimulation with interleukin-3, inteleukin-33, interleukin-5, interleukin-2, nerve growth factor, anti-IgE antibody (6061P, Hybridoma Labs, Maryland) or fmet-leu-phe (FMLP) and the sample title indicates the mode and length of stimulation.

overall_design: Basophils were isolated from peripheral blood, purified to high homegeneity (99%), and stimulated in vitro.


title: Biomarker-based classification of bacterial and fungal whole-blood infections in a genome-wide expression study

status: Public on Mar 11 2015

city: Jena

first: Andreas

last: Dix

address: Beutenbergstraße 11a

institute: Hans-Knöll-Institut

summary: Sepsis is a clinical syndrome that can be caused by bacteria or fungi. Early knowledge on the nature of the causative agent is a prerequisite for targeted anti-microbial therapy. Besides currently used detection methods like blood culture and PCR-based assays, the analysis of the transcriptional response of the host to infecting organisms holds great promise. In this study, we aim to examine the transcriptional footprint of infections caused by the bacterial pathogens Staphylococcus aureus and Escherichia coli and the fungal pathogens Candida albicans and Aspergillus fumigatus in a human whole-blood model. Moreover, we use the expression information to build a random forest classifier to determine if the pathogen is bacterial, fungal or neither of the two. After normalizing the transcription intensities using stably expressed reference genes, we filtered the gene set for biomarkers of bacterial or fungal blood infections. This selection is based on differential expression and an additional gene relevance measure. In this way, we identified 38 biomarker genes, including IL6, SOCS3, and IRG1 which were already associated to sepsis by other studies. Using these genes, we trained the classifier and assessed its performance. It yielded a 96% accuracy (sensitivities >93%, specificities >97%) for a 10-fold stratified cross-validation and a 92% accuracy (sensitivities and specificities >83%) for an additional dataset comprising Cryptococcus neoformans infections. Furthermore, the noise-robustness of the classifier suggests high rates of correct class predictions on datasets of new species. In conclusion, this genome-wide approach demonstrates an effective feature selection process in combination with the construction of a well-performing classification model. Further analyses of genes with pathogen-dependent expression patterns can provide insights into the systemic host responses, which may lead to new anti-microbial therapeutic advances.

overall_design: Analysis of innate immune activation on the basis of gene expression of whole blood cells during ex vivo whole blood infection with bacterial (Staphylococcus aureus, Escherichia coli) and fungal pathogens (Candida albicans, Aspergillus fumigatus) in comparison to mock-treated blood.

first: Kerstin

last: Hünniger

last: Weber

first: Reinhard

last: Guthke

first: Oliver

last: Kurzai

first: Jörg

last: Linde


title: Genome-wide hsa-miR-191 target profile [chip]

status: Public on Mar 01 2015

city: Austin

first: Vishy

last: Iyer

state: TX

address: 2500 Speedway Dr. MBB 3.212

department: Molecular Biosciences

institute: University of Texas at Austin

type:
Other
Expression profiling by array

summary: Profile of transcripts isolated from Ago2 immunoprecipitation following transfection with miR-191 mature duplex and gene expression profile following transfection with miR-191 mature duplex

overall_design: RNA isolated from Ago2 immunopreciptation from HeLa cells 24 hours after transfection of mature miR-191 duplexes. Examination of mRNA levels in HeLa cells following transfection of miR-191 mature duplex or mock transfection

first: Damon

last: Polioudakis


title: The BET Bromodomain inhibitor OTX015 affects pathogenetic pathways in pre-clinical B-cell tumor models and synergizes with targeted drugs

first: Francesco

last: Bertoni

summary: assess the efficacy of OTX015, a BET Bromodomain inhibitor,with respect to various lymphoma models, and to characterize its mechanism of action

overall_design: GEP analysis of 2 lymphoma cell lines with and without treatment with BET Inhibitor and 22 lymphoma cell lines without treatment (basal level).

first: Michela

last: Boi

first: Eugenio

last: Gaudio

first: Paola

last: Bonetti

first: Andrea

last: Rinaldi

first: Ivo

last: Kwee


title: BCL6 orchestrates Tfh differentiation via multiple distinct mechanisms

city: Cleveland

first: Peter

last: Wilkinson

address: 2103 Cornell Road

department: Pathology / Systems Biology & Bioinformatics

institute: Case Western Reserve University

summary: Tfh cells are required for T cell help to B cells, and BCL6 is the defining transcription factor of Tfh cells. However, the functions of Bcl6 in Tfh have largely remained unclear. Here we defined the BCL6 cistrome in primary human germinal center Tfh cells to assess mechanisms of BCL6 regulation of CD4 T cells, comparing and contrasting BCL6 function in T and B cells. BCL6 primarily acts as a repressor in Tfh cells, and BCL6 binding was associated with control of Tfh cell migration and repression of alternative cell fates. Interestingly, although some BCL6 bound genes possessed BCL6 DNA binding motifs, many BCL6-bound loci were instead characterized by the presence of DNA motifs for AP1 or STAT. AP1 complexes are key positive downstream mediators of TCR signaling and external stimuli. We show that BCL6 can directly bind AP1, and BCL6 depends on AP1 for recruitment to BCL6 binding sites with AP1 motifs, suggesting that BCL6 subverts AP1 activity. These findings reveal that BCL6 has broad and multifaceted effects on Tfh biology, and provide insight into how this master regulator mediates distinct cell-context dependent phenotypes.

overall_design: Sorted naïve tonsil cells were activated with anti-CD3+CD28 Ab coated beads and transduced with BCL6 or control lentiviral vectors as described. RNA was isolated at day 5 following LV infection and microarrays performed as discussed herein. RNA was isolated with the RNeasy Micro Kit (QIAGEN). The quantity and quality of the RNA were confirmed with a NanoDrop 2000c (Thermo Fisher Scientific) and an Experion Electrophoresis System (Bio-Rad). Samples (20 ng) were amplified with Illumina MessageAmp II aRNA Amplification Kits (Ambion), hybridized to HumanHT-12_V4 BeadChips (Illumina), and quantified with Genome Studio (Illumina). Normalized data (heatmap of blood cells) or raw data (heatmap of tonsil cells and Volcano plot) were analyzed with the GenePattern software suite.

first: K

last: Hatzi

first: J

last: Nance

first: M

last: Kroenke

last: Bothwell

first: E

last: Haddad

first: A

last: Melnick

first: S

last: Crotty

first: X

last: Sun

first: P

first: L

last: Pan

last: Cameron


title: Gene expression analysis of bone marrow mesenchymal stromal cells from myelodysplastic syndrome (MDS) patients and normal controls

city: Daejeon

first: Seungwoo

last: Hwang

address: 52 Eoeun-dong Yuseong-gu

department: Korean Bioinformation Center

institute: Korea Research Institute of Bioscience and Biotechnology

summary:
Myelodysplastic syndrome (MDS) is a group of heterogeneous clonal stem cell disorders. We hypothesize that gene expression changes in the bone marrow (BM) microenvironment might play a fundamental role in the development and progression of MDS. The goal of the present study is to investigate the differences in gene expression profiles of BM mesenchymal stromal cells (MSCs) between MDS patients and normal individuals, as well as between MDS subtypes. To this end, we applied global gene expression profiling on BM MSCs from adult de novo MDS patients and from controls.
The results suggest that gene expression of the MDS BM microenvironment is difference from control BM. In particular, interferon signaling pathway was shown to be up-regulated in MDS BM. The results also showed altered expression according to disease progression. The present study provides evidence supporting MDS as an immune disease and suggests that BM MSCs are a possible therapeutic target in MDS.

overall_design: The present study include seven adults referred for staging of lymphoma with no evidence of BM involvement as controls, and seven adults diagnosed as de novo MDS cases. The MDS patients consist of three RCMD, three RAEB-1, and one RAEB-2 (abbreviation, RCMD: refractory cytopenia with multilineage dysplasia; RAEB: refractory anemia with excess blasts). Total RNA was isolated from BM MSCs for gene expression analysis that compares the three groups - control (n=7), RCMD (n=3), and RAEB (n=4) - in a pairwise manner.

first: Miyoung

last: Kim

first: Dong

last: Lee


title: Characterization of tumor extracellular vesicle RNA cargo

status: Public on Mar 05 2015

city: Utrecht

first: Jacco

last: Van Rheenen

address: Uppsalalaan 8,

department: Cancer Genomics Netherlands

institute: Hubrecht Institute-KNAW & University Medical Center Utrecht

summary: Comparative RNA profiling between tumor cells and their secreted extracellular vesicles. Results revealed enrichment in genes involved in cellular migration and metastasis in extracellular vesicles, in agreement with their role as mediators of tumor progression.

overall_design: Mice were orthotoplically transplanted with MDA-MB-231 Breast Adenocarcinoma cells. Cells and extracellular vesicles (EVs) from the resulting tumors were isolated. EVs were characterized by electron microscopy and Nanoparticle Tracking Analysis before total RNA isolation for comparative analysis with cellular RNA. Three biological replicates were analyzed in (technical) duplicate.

first: Anoek

last: Zomer

first: Carrie

last: Maynard

first: Frederik

last: Verweij

first: Alwin

last: Kamermans

first: Ronny

last: Schäfer

first: Evelyne

last: Beerling

first: Raymond

last: Schiffelers

first: Elzo

last: de Wit

first: Jordi

last: Berenguer

first: Saskia

middle: I

last: Ellenbroek

first: Thomas

last: Würdinger

first: Michiel

last: Pegtel

last: van Rheenen


title: Isolation of fetal human CD140a and O4-defined oligodendrocyte progenitor cells.

status: Public on Mar 04 2015

city: Buffalo

first: Fraser

middle: James

last: Sim

state: NY

address: 3435 Main Street

department: Pharmacology

institute: University at Buffalo

summary: Human fetal tissue dissociates between 18-22wk gestational age were FACS sorted on the basis of CD140a (PDGFRA) and O4 antigens. Each population was profiled immediately following FACS.

overall_design: 20 samples, 4 groups (FACS-sorted cell populations), between 3 and 6 replicates in each group, each replicate is from a separate patient sample

first: Suyog

middle: U

last: Pol

first: Melanie

last: O'Bara

first: Bansi

middle: H

last: Vedia


title: Vector and Brown fat lncRNA 1 (Blnc1) expressing differentiated brown adipocytes

status: Public on Feb 28 2015

city: Ann Arbor

first: Jiandie

last: Lin

address: 210 Washtenaw Avenue

department: Life Sciences Institute

institute: University of Michigan

summary:
Blnc1 is a novel nuclear lncRNA that promotes brown and beige adipocyte differentiation and function. Blnc1 forms a ribonucleoprotein complex with transcription factor EBF2 to stimulate the thermogenic gene program. Further, Blnc1 itself is a target of EBF2, thereby forming a feedforward regulatory loop to drive adipogenesis toward thermogenic phenotype.
We used microarrays to elucidate the role of Blnc1 on brown adipocyte differentiation and the induction of the thermogenic gene program.

overall_design: Brown adipocytes expressing vector or brown fat lncRNA 1 (blnc1) were differentiated for 6 days and harvested for RNA isolation and microarray using Affymetrix Mouse MG-430 PM Strip arrays. Two replicated samples were included in this study.

first: Xu-Yun

last: Zhao

first: Siming

last: Li

first: Guo-Xiao

last: Wang

first: Qi

last: Yu


title: Preclinical antitumor activity of ST7612AA1: a novel second generation oral histone deacetylase (HDAC) inhibitor

first: Francesco

last: Bertoni

summary: assess the efficacy of ST7612AA1 oral pan-histone deacetylase inhibitor (HDACi),  with respect to various solid and haematological tumors, and to characterize its mechanism of action

overall_design: GEP analysis of two lymphoma cell lines with and without treatment

first: Elena

last: Bernasconi

first: Andrea

last: Rinaldi

first: Loredana

last: Vesci

first: Ivo

last: Kwee


title: Gene expression profiles of dasatinib-resistant and dasatinib-sensitive pancreatic cancer cell lines

status: Public on Feb 24 2015

city: Singapore

first: Phillip

last: Koeffler

address: 14 Medical Drive

country: Singapore

institute: Cancer Science Institute

summary: Gene profiles from three dasatinib-resistant and three dasatinib-sensitive pancreatic cancer cell lines were compared by microarray analysis.

overall_design: RNA from three dasatinib-resistant (MiaPaCa2, Panc1, SU8686) and three dasatinib-sensitive (Panc0504, Panc0403, Panc1005) pancreatic cancer cell lines were extracted. Biological triplicates were employed for each cell line. Complementary DNA microarray analysis was performed using Illumina Human HT-12 v4 BeadChip (Illumina, San Diego, CA) at the National University of Singapore Core Facility following the manufacturer’s instructions.

first: Wenwen

last: Chien

first: Qiao-Yang

last: Sun

first: Kian

last: Lee

first: Ling-Wen

last: Ding

first: Peer

last: Wuensche

first: Lucia

last: Torres-Fernandez

first: Siew

middle: Z

last: Tan

first: Itay

last: Tokatly

first: Norazean

last: Zaiden

first: Lorenz

last: Poellinger

first: Seiichi

last: Mori

first: Henry

last: Yang

first: Jeffrey

middle: W

last: Tyner

first: H


title: Gene expression profile of influenza virus antigen-activated or in vitro stimulated murine CD8+ T cells on day 7

status: Public on Feb 25 2015

city: Sydney

first: Wolfgang

last: Weninger

address: Locked Bag 6, Newtown

institute: Centenary Institute

summary:
The precise timing and pathway of memory CD8+ T cells differentiation from naïve T cells have remained undetermined. We found the smaller cell-size and slower cell cycling cells were segregated from the proliferative larger cell-size activated T cell pool at the peak of infection.
Gene signature of the smaller cell-size slower cycling cells and the large cell-size proliferative cells was compared to the signature of naïve, effector, central and effector memory CD8+ T cells.

overall_design: Total RNA samples were prepared from sorted populations of larger or smaller cell-sized cells from spleens of influenza virus PR8-OVA-infected mice on day 7 p.i. or from in vitro 7 days culture after stimulation with plate-bound anti-CD3ε (1.0 μg ml−1) and anti-CD28 mAb (0.5 μg ml−1). Effector T-cell control samples were prepared from SIINFEKL (100 ng ml−1) stimulated OT-I cells after 4 days of in vitro culture with rIL-2 (10 ng/ml) and sorted as CD8+CD44hiCD62Llo. Control bona fide effector memory and central memory T cells were sorted from the spleens of PR8-OVA-infected mice on day 42 p.i. Naive cells were sorted as CD8+CD44loCD62Lhi cells from uninfected C57BL/6 mice.

first: Ichiko

last: Kinjyo

first: Jim

last: Qin

first: Paulus

last: Mrass

first: William

last: Ritchie

first: Atsushi

last: Doi


title: EZH2 Overexpression in Breast Cancer is due to MicroRNA-Dependent Suppression of ZBTB4

status: Public on Mar 02 2015

city: Little Rock

first: Kyounghyun

last: Kim

state: AR

address: Rm 318 CI.3329 4104 Outpatient Circle

department: Pharmacology & Toxicology

institute: University of Arkansas Medical Sciences

summary: In order to Sp1 and EZH2-specific gene expression pattern in breast cancer, small interfering RNA for Sp1 and EZH2 was transfected in MDA-MB-231 cells.

overall_design:
Four groups of samples are included:
1. si control (siCT_1, siCT_2, siCT_3).
2. siSp1 (siSp1_1, sisSp1_2, siSp1_3).
3. si control (siCT_A, siCT_B, siCT_C).
4. siEZH2 (siZEH2_1, siZEH2_2,siEZJ2_3).
Gene expression profiles of Sp1 and EZH2 depleted cells were compared to that of siRNA controls. Experiments were performed in MDA-MB-231 cells.

first: Stephen

last: Safe


title: Gene expression profiling of HDLM-2 Hodgkin lymphoma cell line after in vitro and in vivo treatment with Givinostat in combination with Sorafenib

city: Milan

first: Loris

last: De Cecco

address: via Venezian 1

country: Italy

institute: IRCSS Istituto Nazionale Tumori

summary: Relapsed/refractory Hodgkin lymphoma (HL) is an unmet medical need requiring new therapeutic options. Interactions between the histone deacetylase inhibitor Givinostat and the RAF/MEK/ERK inhibitor Sorafenib were examined in HDLM-2 and L-540 HL cell lines. Exposure to Givinostat/Sorafenib induced a synergistic inhibition of cell growth (range, 70- 80%) and a dramatic increase in cell death (up to 96%) due to increased H3 and H4 acetylation and strong mitochondrial injury. Gene expression profiling indicated that the synergistic effects of Givinostat/Sorafenib treatment are associated with the modulation of cell cycle and cell death pathways. Exposure to Givinostat/Sorafenib resulted in sustained production of reactive oxygen species (ROS) and activation of necroptotic cell death. The necroptosis inhibitor Necrostatin-1 prevented Givinostat/Sorafenib-induced ROS production, mitochondrial injury, activation of BH3-only protein BIM and cell death. Knockdown experiments identified BIM as a key signaling molecule that mediates Givinostat/Sorafenib-induced oxidative death of HL cells. Furthermore, in vivo xenograft studies demonstrated a 50% reduction in tumor burden (P < 0.0001), a 5- to 15-fold increase in BIM expression (P ≤.0001) and a 4-fold increase in tumor necrosis in Givinostat/Sorafenib-treated animals compared to mice that received the single agents. These results provide a rationale for exploring Givinostat/Sorafenib combination in relapsed/refractory HL.

overall_design:
The Hodgkin lymphoma cell line HDLM-2 was obtained from the DSMZ (Braunschweig, Germany, EU). Cells were routinely maintained in RPMI medium 1640 (Lonza, Basel, Switzerland) supplemented with 20% FBS (Lonza) and 2 mM glutamine (Lonza). Cells were maintained at 37°C in a water-saturated atmosphere of 5% CO2 in air. 10x10^6 HDLM-2 cells were seeded in 75 cm2 flask and, after 24 hrs, cells were treated with 100 nM Givinostat (Italfarmaco SpA, Milan, Italy, EU) and/or 5 µM sorafenib (Bayer, Berlin,
Germany, EU) in culture medium for 24 hours. At the end of treatment, cells were collected and RNA was extracted.

first: L

first: A

last: Anichini

first: G

last: Stirparo


title: MYCOPLASMAL DNA METHYLTRANSFERASES ALTER THE EPIGENETIC LANDSCAPE IN HUMAN CELLS

city: La Jolla

first: Andrei

last: Chernov

address: 9500 Gilman Dr

department: Anesthesiology

institute: University of California San Diego

summary: Aberrant DNA methylation is frequently observed in human disease, particularly in cancer, but the underlying pathogenic mechanisms are not well understood. We demonstrate that mycoplasmal 5-methylcytosine DNA methyltransferases (MTases) can induce epigenetic alterations in human cells. We expressed the CG-specific Mhy1 and the GATC-specific Mhy2 Mycoplasma hyorhinis MTases in cultured human cells, and determined that both enzymes penetrated the cell nuclei and induced a 3.5-fold and a 2-fold increase in genome-wide methylation, respectively. We next mapped genomic locations of these de novo methylation marks in the human genome. Sequence analysis suggested that most gene loci became hypermethylated, except the promoters of actively transcribed genes, which appeared to be protected from methylation by these exogenous MTs. Significant aberrant de novo methylation of cytosines within the GATC sequences were induced by Mhy2 in non-cancer HTR8/SVneo trophoblasts. This included a striking activation of cell proliferation pathways via upregulation of c-JUN and MYC oncogenes and transcription factors, including ATF3, KLF6 and DKK1. Our findings unveil a novel link between the microbiome and human epigenetics with special relevance to cancer epigenetics.

overall_design: Gene expression profiling of total RNAs extracted from human fibrosarcoma HT1080 cells and human transformed first trimester extravillous HTR8/SVNeo trophoblast cells expressing Mycoplasma hyorhinis DNA methyltransferases

middle: V

first: Alex

middle: Y

last: Strongin


title: LRH1 silencing inhibits human colon cancer growth.

city: Houston

first: Paul

last: Webb

address: 6670 Bertner Ave

department: Genomic Medicine

institute: Houston Methodist Research Institute

summary:
This study was undertaken to better determine the function of LRH-1 (NR5A2) in the colorectal cancers (CRC) through inducible shRNA-mediated knockdown within well-established CRC cell line Caco-2
Our work is the first to demonstrate that silencing of LRH-1 in established human CRC cell lines impairs proliferation though G0/G1 phase prolongation, and alteration in diverse cellular pathways consistent with the critical role of LRH-1 in CRC.

overall_design: Two separate DNA sequences targeting the LRH-1 LBD- were cloned into parent vector pTripZ RHS4696 (Open Biosystems), with incorporation of silencing vector confirmed by fluorescent assay for marker TurboRFP. Non-silencing control cell lines were produced similarly using manufacturer’s vector (Open Biosystems, RHS4743). Cells were plated at a concentration of 100,000 cells per ml in 12 well plates and allowed to attach overnight.  shRNA expression was induced by the addition of 5 μg/ml of doxycycline when the cells approached 75% confluence.  Cells were harvested at 96 hours post induction using Trizol reagent (Life Technologies), and Total RNA harvested using PureLink RNA Mini Kit (Ambion) according to the manufacturer’s protocol.

first: Douglas

last: Sieglaff


title: Gene expression profiling of L-540 Hodgkin lymphoma cell line after in vitro and in vivo treatment with Givinostat in combination with Sorafenib

overall_design:
The Hodgkin lymphoma cell line L-540 was obtained from the DSMZ (Braunschweig, Germany, EU). Cells were routinely maintained in RPMI medium 1640 (Lonza, Basel, Switzerland) supplemented with 20% FBS (Lonza) and 2 mM glutamine (Lonza). Cells were maintained at 37°C in a water-saturated atmosphere of 5% CO2 in air. 10x10^6 L-540 cells were seeded in 75 cm2 flask and, after 24 hrs, cells were treated with 100 nM Givinostat (Italfarmaco SpA, Milan, Italy, EU) and/or 5 µM sorafenib (Bayer, Berlin,
Germany, EU) in culture medium for 24 hours. At the end of treatment, cells were collected and RNA was extracted.


title: Scramble and Brown fat lncRNA 1 knockdown (shBlnc1) expressing differentiated brown adipocyte

first: xuyun

last: zhao

state: Michigan

address: 210 washtenaw ave

institute: Life Sciences Institute

summary:
Blnc1 is a novel nuclear lncRNA that promotes brown and beige adipocyte differentiation and function. Blnc1 forms a ribonucleoprotein complex with transcription factor EBF2 to stimulate the thermogenic gene program. Further, Blnc1 itself is a target of EBF2, thereby forming a feedforward regulatory loop to drive adipogenesis toward thermogenic phenotype.
We used microarrays to elucidate the role of Blnc1 on brown adipocyte differentiation and mitochondrial function.

overall_design: Brown adipocytes expressing Scramble or brown fat lncRNA 1 knockdown (shBlnc1) were differentiated for 6 days and harvested for RNA isolation and microarray using Affymetrix Mouse MG-430 PM Strip arrays. Two replicated samples were included in this study.

first: Xu-Yun

last: Zhao

first: Siming

last: Li

first: Guo-Xiao

last: Wang

first: Qi

last: Yu

first: Jiandie

last: Lin


title: Genome-wide gene expression analysis in primary ciliary dyskinesia patients

city: Poznań

first: Maciej

last: Geremek

address: Strzeszyńska

country: Poland

institute: IGCZ PAN

summary: We performed whole genome gene expression profiling in bronchial biopsies from PCD patients. We used the Quality Threshold clustering algorithm to identify groups of genes that revealed highly correlated RNA expression patterns in the biopsies. The largest cluster contained 372 genes and was significantly enriched for genes related to cilia. The database and literature  search showed that 16250 genes in this cluster were known cilia genes, strongly indicating that the remaining 21022 genes were likely to be new cilia genes. The tissue expression pattern of the 210 new cilia genes and the 162 known genes was consistent with the presence of motile cilia in a given tissue. Analysis of the upstream promotor sequences revealed evidence for RFX transcription factors binding site motif in both subgroups.

overall_design: Total RNA obtained from 6 primary ciliary dyskinesia patients and 9 control individuals


title: Genome-wide analysis of dexamethasone treated substrates in HeLa cell

status: Public on Feb 22 2015

city: Seoul

first: Hana

last: Cho

address: Anam 5ga, Sungbukku

department: School of Life Sciences and Biotechnology

institute: Korea University

summary: Analysis of dexamethasone treated substrates during 3 hr in HeLa cell.

overall_design: Total RNA obtained from HeLa cells with treatement of dexamethasone during 3hr. The up- or down-regulated transcripts were compare to control (DMSO) treated HeLa cell RNA extract. Significant transcripts were confirmed by replication

first: Ok

last: Park


title: Ex vivo effects of Tenofovir on four vaginal epithelial cell lines

status: Public on Feb 23 2015

city: Seattle

first: Lamar

last: Ballweber Fleming

state: WA

address: 1100 Fairview Ave N

department: VIDD

institute: Fred Hutchinson Cancer Res Ctr

summary: In MTN-007, a phase 1, randomized, double-blinded rectal microbicide trial, we used systems genomics/proteomics to determine the effect of tenofovir 1% gel, nonoxynol-9 2% gel, placebo gel or no treatment on rectal biopsies taken at baseline, after one application or after seven daily applications (15 subjects/arm).  Experiments were repeated using primary vaginal epithelial cells from four healthy women.

overall_design: 36 Arrays (3 primary vaginal epithelial cell lines from healthy women donors,  cultured with or without 50uM or 500 uM Tenofovir for 1,4,7, or 14 days per donor cell line.  A no treatment, culture media only control was included for each donor cell line and for each time point.

first: Florian

last: Hladik

last: Ballweber

first: M

last: McElrath

first: Ian

last: McGowan


title: Effects of siRNA targeting PRKCD in breast cancer cells

city: Lund

first: Christer

last: Larsson

address: Medicon Village, Bldg 404:C3

department: Laboratory Medicine

institute: Lund university

summary: The aim was to identify genes that were commonly influenced by a siRNA targeting PRKCD in breast cancer cell lines.

overall_design: MDA-MB-468 and BT-549 breast cancer cell lines were treated with control siRNA or siRNA targeting PRKCD. Three samples in each group were analyzed.


title: Defined conditions for the isolation and expansion of basal prostate stem cells of mouse and human origin [human]

status: Public on Feb 20 2015

city: Heidelberg

first: Eisen

last: Christian

state: (Click to Select US State)

address: Im Neuenheimer Feld 280

institute: German Cancer Research Center

summary: Isolation and culture of primary prostate epithelial stem/progenitor cells (PESC) has been proven difficult and ineffective. Here we present methods to grow and expand both murine and human basal PESCs long-term in serum- and feeder-free conditions. The method enriches for adherent mouse basal PESCs with a Lin-Sca1+ CD49f+Trop2high phenotype. Progesterone and sodium selenite are additionally required for the growth of human Lin-CD49f+Trop2high PESCs.  The gene expression profiles of expanded basal PESCs show similarities to ES cells and Lamin B1 and PRDX1 were identified as novel PESC markers. If transplanted in combination with urogenital sinus mesenchyme, expanded mouse and human PESCs generate ectopic prostatic tubules demonstrating their stem cell activity in vivo. The novel methods will facilitate the cellular, molecular and genomic characterization of normal and pathologic prostate glands of mouse and human origin.

overall_design: Human prostate cells derived from two individual patients were seperately cultured under spheroid and adherent stem cell conditions and subsequently used for RNA extraction

first: Christian

last: Eisen

first: Thomas

last: Höfner


title: Systems Biology Analysis of Tenofovir 1% Gel in a Phase I Rectal Microbicide Trial

overall_design: 192 Arrays (8 donors per treatment group, 2 biopsy sites per donor (9cm and 15 cm), biopsies taken at baseline, after a single application, and after 7 daily applications)

first: Adam

last: Burgener

first: Raphael

last: Gottardo

first: Slim

last: Fourati

first: James

last: Dai

first: Mark

last: Cameron

first: Lucia

last: Vojtech

first: Johanna

last: Strobl

first: Sean

last: Hughes

first: Craig

last: Hoesley

first: Ross

last: Cranston

first: Philip

last: Andrew

first: Jeanna

last: Piper

first: T

middle: B

last: Ball

first: David

middle: R

last: Friend

first: Kenneth

last: Mayer


title: Genome-wide analysis of PARKIN deficient patient fibroblast and iPSC lines

city: novato

first: Ying

last: Pei

state: ca

address: 8001 redwood blvd

institute: Buck Institute

summary: Analysis of whole genome gene expression in control and PARKIN patient lines. The hypothesis tested in the present study was that the deficient of PARKIN expression affects multiple pathways. Results provide important information on relationship between PARKIN and mitochondria related gene expression.

overall_design: Total RNA obtained from patient fibroblast and iPSC compare to control fibroblast and iPSC.

first: Xianmin

last: Zeng