title: Candidate Vaccine Assessment in a pH1N1 Rhesus Macaque Challenge Model

first: Jason

last: Skinner

summary: A mixed-aerosol pH1N1 (Cal04) challenge of rhesus macaques was establised to serve as a pre-clinical model for the evaluation of candidate vaccines.  After characterizing the clinical signs and immune responses associated with pH1N1 challenge in naïve rhesus macaques, a follow-up study assessing 2 candidate vaccines was performed.

overall_design: This study has 2 phases: 1) Model Establisment consisting of 3 groups: Unvaccinated Live Challenge (n=3, Unvaccinated UV-inactivated Challenge (n=3), Previously Vaccinated Live Challenge (n=3) which were sampled at 2 baseline timepoints Day -7 and Day 0.  Following the H1N1 Challenge, samples were collected at day 1,2,5,8,14,20. 2) Candidate Vaccine Assessment consisting of four groups: Previously Vaccinted with anti-CD40-NP5+PolyICLC (n=4), Previously vaccinated with CD40-HA+PolyICLC (n=4), Previously vaccinated with commercial mismatched Fluzone (n=4), Previously vaccinated with Media+PolyICLC alone (n=4). Daseline samples were collected at Day -7 and 0 (baseline) and Day 1,3,6,14,20 post-challenge.


title: Gene expression analysis of human medulloblastoma and neural stem cells

status: Public on Oct 23 2014

city: Perth

first: Kim

middle: Warwick

last: Carter

state: Western Australia

address: 100 Roberts Road, Subiaco

country: Australia

institute: Telethon Kids Institute

summary:
Medulloblastoma is the most common form of malignant paediatric brain tumour and is the leading cause of childhood cancer related mortality. The four molecular subgroups of medulloblastoma that have been identified – WNT, SHH, Group 3 and Group 4 - have molecular and topographical characteristics suggestive of different cells of origin. Definitive identification of the cell(s) of origin of the medulloblastoma subgroups, particularly the poorer prognosis Group 3 and Group 4 medulloblastoma, is critical to understand the pathogenesis of the disease, and ultimately for the development of more effective treatment options.
The gene expression profiles of normal human neural tissues and cell types representing a broad neuro-developmental continuum, were compared to those of two independent cohorts of primary human medulloblastoma specimens.

overall_design: Total RNAwas extracted from 19 human primary medulloblastoma specimens, one human normal fetal brain (NFB) sample consisting of total RNA pooled from 50 individuals (embryonic week 22-33), two normal human fetal germinal matrix (NFGM) samples obtained from the lateral sub-ventricular zones of two 16 week old  male fetuses, and  CD133+ neural stem cells and CD133-  neural progenitor cells isolated from embryonic stem cell derived neurospheres from three individuals. Gene expression profiling was carried out using Affymetrix U133A genechips.

first: Cornelia

middle: M

last: Hooper

first: Susan

last: Hawes

first: Ursula

middle: R

last: Kees

first: Nicholas

middle: G

last: Gottardo

first: Peter

middle: B

last: Dallas


title: Quantitative mRNA expression comparison of Hepatitis C Virus replicon (2a) on Huh7.5 cell lines

status: Public on Oct 21 2014

city: Seoul

first: Jun-Seok

last: Lee

address: 39-1 Hawolgok-dong Seungbuk-gu

country: South Korea

institute: Korea Institute of Science and Technology (KIST)

summary: We developed transcriptome expression assisted non-directed proteome profiling (TEAnDPP) method to investigate host-pathogen interaction. Analysis of HCV replicon induced host-cell metabolism perturbation at gene expression level. Gene enrichment analysis on DEG revealed disulfide formation related genes were significantly enriched. Based on this observation, we addminitrated thiol reactive chemical probes to visualize reactive thiol profile in live cell, and observed unique reactivity profile. Using SILAC-based quantitative profiling method, we identified 26 proteins that are labeled by iodoacetamide probes. Among these proteins, we discovered t-plastin was upregulated in APC140 cells, and its knock-down experiment showed significant HCV replication inhibition effect. In short, TEAnDPP strategy demonstrated its usefulness in host-pathogen interaction study for HCV infection.

overall_design: Total RNA obtained from APC140 (stable cell line expressing HCV2a replicon) was compared to vehicle cell line (Huh7.5).

first: Young-Hwa

last: Yoo


title: Profiling of exome mutations associated with progression of HBV-related hepatocellular carcinoma

status: Public on Oct 19 2014

city: Suwon

first: Hyun Goo

last: Woo

address: 164 Worldcup-ro Yeongtong-gu

institute: Ajou University School of Medicine

summary: We profiled the mutations and gene expressions of early and advanced hepatocellular carcinoma (HCC) related with Hepatitis B-viral infection. Integrative analysis was performed with whole-exome sequencing and gene expression profiles of the 12 cases of early and advanced HCCs and paired non-tumoral adjacent liver tissues.

overall_design: 12 HCC Samples

first: HG

last: WOO


title: Expression profiling of metaplastic carcinoma of the breast

status: Public on Oct 31 2014

city: Pieve Emanuele

first: Charlotte

middle: K Y

last: Ng

state: MI

address: Via Rita Montalcini 4

department: Biomedical Sciences

country: Italy

institute: Humanitas University

overall_design: Metaplastic breast carcinoma (MBC) is a rare and aggressive histologic type of breast cancer, preferentially displaying a triple-negative phenotype (i.e. lacking estrogen receptor, progesterone receptor and HER2 expression). We sought to define the transcriptomic heterogeneity of MBCs on the basis of current gene expression microarray-based classifiers and to determine whether MBCs display gene copy number profiles consistent with those of BRCA1-associated breast cancers.

first: Britta

last: Weigelt

first: Anne

last: Vincent-Salomon

first: Jorge

middle: S

last: Reis-Filho


title: Gene expression profiling of Glioma Stem Cells (GSCs) and their differentiated cell counterparts after MG132 treatment

status: Public on Oct 15 2014

first: Young Dong

state: Gyeonggi-do

address: 28 Yeon-gun dong Jongnogu

department: Biomedical Science

institute: Seoul National University

summary: Analysis of genes in GSCs and differentiated cells that are induced by MG132 treatment.

overall_design: Total RNAs were isolated from GSCs and differentiated cells after MG132 or DMSO treatment for 6 hrs in serum-free media

first: Yong

middle: T

last: Kwon

first: Young

middle: D


title: Analysis of gene expression profiles of human melanoma A375 cells with or without CD10 overexpression

status: Public on Oct 18 2014

city: Fukuoka

first: Junna

last: Oba

address: 3-1-1 Maidashi, Higashi-ku

department: Dermatology

country: Japan

institute: Kyushu University

summary: Analysis of effect of CD10 in melanoma at gene expression level. The hypothesis tested in the present study was that CD10 promotes melanoma tumor progression. Results provide important information of the significant gene expression change between CD10-transfected and mock-transfected A375 cells, such as significantly increased genes included those related to anti-apoptosis, angiogenesis and cell proliferation.

overall_design: Total RNA obtained from CD10-transfected A375 melanoma cells was that from compared to mock-transfected A375 cells.

first: Takeshi

last: Nakahara


title: Breast Cancer Gene Expression Data from Frankfurt Series

status: Public on Oct 14 2014

city: Frankfurt

first: Thomas

last: Karn

address: Theodor-Stern-Kai 7

country: Germany

summary: Pooling of microarray datasets seems to be a reasonable approach to increase sample size when a heterogeneous disease like breast cancer is concerned. Different methods for the adaption of datasets have been used in the literature. We have analyzed influences of these strategies using a pool of 3,030 Affymetrix U133A microarrays from breast cancer samples. We present data on the resulting concordance with biochemical assays of well known parameters and highlight critical pitfalls. We further propose a method for the inference of cutoff values directly from the data without prior knowledge of the true result. The cutoffs derived by this method displayed high specificity and sensitivity. Markers with a bimodal distribution like ER, PgR, and HER2 discriminate different biological subtypes of disease with distinct clinical courses. In contrast, markers displaying a continuous distribution like proliferation markers as Ki67 rather describe the composition of the mixture of cells in the tumor.

overall_design: Fresh frozen surgical biopsy samples from consecutive patients were analyzed on Affymetrix HGU133A

first: Uwe

last: Holtrich

first: Achim

last: Rody


title: Effects of SPOP on gene expression in prostate cancer

status: Public on Oct 10 2014

city: Houston

first: Nicholas

last: Mitsiades

state: Texas

address: One Baylor Plaza

department: Medicine-Hematology & Oncology

country: USA

institute: Baylor College of Medicine

summary: SPOP is a ubiquitin ligase adaptor frequently mutated in prostate cancer. It is involved in ubiquitination and degradation of substrate proteins. We examined the impact of wild-type and mutant SPOP on the transcriptional profile of prostate cancer cells.

overall_design: We cloned several naturally occurring (in human prostate cancer) SPOP mutants and expressed the corresponding constructs in prostate cancer cells. Our experimental conditions were: Human prostate cancer cells (LNCaP-Abl), transfected with control vector, SPOP-wt, and any of the following mutants: SPOP-F102C, SPOP-F133V, SPOP-F133L (2-4 biological replicates each). We analyzed their gene expression profiles for differences induced by SPOP-wt vs SPOP-mutant.

first: Chuandong

last: Geng

first: Kimal

last: Rajapakshe

first: Shrijal

last: Shah

first: John

last: Shou

first: Vijay

last: Eedunuri

first: Christopher

last: Foley

first: Warren

last: Fiskus

first: Mahitha

last: Rajendran

first: Sue

middle: A

last: Chew

first: Martin

last: Zimmermann

first: Richard

last: Bond

first: Bin

last: He

first: Cristian

last: Coarfa


title: Repeat elements study in pluripotent stem cells [expression array]

status: Public on Oct 09 2014

city: Nantong

first: Gangcai

last: Xie

state: Jiangsu

address: Number 9, Se Yuan Road

department: Medical school

country: China

institute: Nantong University

summary: We surveyed RNA-Seq data to identify those TEs that are transcriptionally active uniquely in human pluripotent cells. We identified one endogenous retrovirus (HERV-H) family, uniquely found in primates as being unusually abundant in the transcriptome. The microarray data provided is to support our human naive cell hypothesis.

overall_design: Total of 18 samples of the human ESC line H9 were analyzed for gene expression.

first: Jichang

last: Wang

first: Manvedra

last: Singh

first: Avazeh

last: Ghanbarian

first: Tamás

last: Raskó

first: Attila

last: Szvetnik

first: Huiqiang

last: Cai

first: Daniel

last: Besser

first: Alessandro

last: Prigione

first: Nina

last: Fuchs

first: Gerald

last: Schumann

first: Wei

last: Chen

first: Matthew

middle: C

last: Lorincz

first: Zoltán

last: Ivics

first: Laurence

last: Hurst

first: Zsuzsanna

last: Izsvák


title: PMCA2 Regulates HER2 Expression, Cell-Surface  Localization and Signaling, and Promotes HER2-  Mediated Breast Cancer

status: Public on Oct 22 2014

city: New Haven

first: Jaekwang

last: Jeong

address: 1 Gilbert St.

department: Internal Medicine

institute: Yale University

summary: In the normal breast, PMCA2 transports calcium into milk. It is also  upregulated in breast cancer cells and high tumor levels predict increased  mortality in patients. In this study, we examined interactions between PMCA2  and HER2. We find that PMCA2 and a scaffolding protein, NHERF1, interact  together with HER2 in specific membrane domains protruding from the surface of  breast cancer cells. Knocking down PMCA2 or NHERF1 increases intracellular  calcium and leads to the ubiquitination, endocytosis and degradation of HER2  after receptor activation. This is associated with reductions in HER2 expression  and signaling. Manipulating PMCA2 levels regulates proliferation and apoptosis  of breast cancer cells in vitro and knocking out PMCA2 dramatically inhibits the  formation of hyperplasia and tumors in MMTV-Neu mice.

overall_design: Gene expression profiling was performed on control SKBR3 cells vs. PMCA2, NHERFR1 and HER2 knock down cells. Each group has 6 duplicates.

first: Joshua

last: VanHouten

first: Pamela

last: Dann

first: Wonnam

last: Kim

first: Catherine

last: Sullivan

first: Herbert

last: Yu

first: Lance

last: Liotta

first: Virginia

last: Espina

first: David

last: Stern

first: Peter

last: Friedman

first: John

last: Wysolmerski


title: Specific extracellular matrix remodeling signature of colon hepatic metastases [HG-U133B]

city: Montpellier Cedex 5

first: Pierre

last: Martineau

address: 208 Rue des Apothicaires

department: IRCM

country: France

institute: Inserm

summary: To identify genes implicated in metastatic colonization of the liver in colorectal cancer, we collected pairs of primary tumors and hepatic metastases before chemotherapy in 13 patients. We compared mRNA expression in the pairs of patients to identify genes deregulated during metastatic evolution. We then validated the identified genes using data obtained by different groups. The 33-gene signature was able to classify 87% of hepatic metastases, 98% of primary tumors, 97% of normal colon mucosa, and 95% of normal liver tissues in six datasets obtained using five different microarray platforms. The identified genes are specific to colon cancer and hepatic metastases since other metastatic locations and hepatic metastases originating from breast cancer were not classified by the signature. Gene Ontology term analysis showed that 50% of the genes are implicated in extracellular matrix remodeling, and more precisely in cell adhesion, extracellular matrix organization and angiogenesis. Because of the high efficiency of the signature to classify colon hepatic metastases, the identified genes represent promising targets to develop new therapies that will specifically affect hepatic metastasis microenvironment.

overall_design: 57 samples of patients with stage IV colorectal cancer. We compared using Affymetrix chips gene expression profiles between primary tumors and hepatic metastases

first: Maguy

last: Del Rio

first: Caroline

last: Mollevi


title: Control of breast cancer cell migration by a p63-regulated signaling network (RNA)

city: Dallas

first: Xiaoyu

last: Wang

address: ND3 200, 6001 Forest Park Rd

department: Cancer Center

institute: Ut Southwestern Medical Center

summary: Through analysis of a high-content screen we discovered that mir-203 can impair cell migration by suppressing p63 expression.  We further determined that p63 promotes motility by inducing the expression of multiple target genes.

overall_design: Total RNA  isolated from cell lines with different rated of motility was compared.

first: Gray

last: Pearson


title: Expression data from CD4+ and CD11c+ cells from DO11.10 RAG2-/- mice

status: Public on Oct 07 2014

city: Glasgow

first: Agapitos

last: Patakas

state: Lanarkshire

address: 120 University Place

department: Institute of Infection, Immunity and Inflammation

country: United Kingdom

institute: University of Glasgow

summary:
Abatacept is a recombinant CTLA-4 moleculed fused to a mutated human IgG molecule, which is clinically used in rheumatoid arthritis by inhibiting CD28-costimulation. This study aimed to inverstigate the ability of abatacept -mediated costimulation blockade  to induce antigen-specific tolerance during primary immune responses. This is important as some studies have suggested that costimulation blockade can lead to CD4+ T cell anergy which could be beneficial for early therapy of autoimmune diseases such as rheumatoid arthritis. In addition we also investigated the effect that abatacept has on CD11c+ antigen presenting cells. This is important as costimulation blocakde can affect the biderectional interaction between CD4+ T cells and CD11c+ cells influencing the immunological outcome.
We used microarrays to identify if abatacept treatment leads to antigen specific anergy using transgenic animals and models of priming and oral tolerance that established a synchronised monoclonal response.  In addition this magnified the effect on the CD11c+ antigen presenting cells.

overall_design: This study included 5 experimental groups. DO11.10 RAG2-/- mice have CD4+ T cells specific for the ovalbumin (OVA) peptide OVA323-339. These mice were immunised with CFA/OVA s.c. (primed group) or tolerised by feeding with OVA (50mg/kg) in the drinking water. CD4+ cells were isolated 10 days post immunisation from draining lymph nodes (LNs) of unimmunised (pooled LNs and Spleen), orally tolerised (mesenteric LNs), primed (axillary LNs), primed treated with control IgG (axillary LNs) and primed treated with abatacept (axillary LNs). For CD11c+ cells cells were isolated by pooled secondary lymphoid organs (LNs and spleen).

first: Rui-ru

last: Ji

first: Paul

last: Garside


title: Synergistic anti-tumor activity by association of MEK and PI3K/mTOR blockade with TRAIL in human melanoma

status: Public on Oct 08 2014

city: Milan

first: Loris

last: De Cecco

address: via Venezian 1

institute: IRCSS Istituto Nazionale Tumori

summary: Combining direct anti-tumor effects with targeting of tumor microenvironment is an attractive strategy that may lead to more effective therapies for advanced melanoma.  Here, we tested whether association of TRAIL with co-targeting of MEK and PI3K/mTOR, or with MEK blockade, could have synergistic anti-melanoma activity mediated not only by induction of tumor cell death, but also by effects on the tumor microenvironment.  Drug interaction analysis by the Chou-Talalay approach in a panel of 21 melanoma cell lines indicated that strong synergism could be achieved by association of the MEK1/2 inhibitor AZD6244, the PI3K/mTOR inhibitor NPV-BEZ235 and TRAIL, as well as by the AZD6244/TRAIL combination.  Synergism was observed on most tumors including TRAIL- or inhibitor-resistant melanomas, irrespective of the BRAF, NRAS, p53 and PTEN status, and was explained by enhanced induction of caspase-dependent melanoma apoptosis. The AZD/BEZ/TRAIL and AZD/TRAIL combinatorial treatments induced strong modulation of key apoptosis regulators along the extrinsic and intrinsic cell death pathways, including c-FLIP down-regulation, caspase-8 cleavage, BIMs and BAXa upregulation, clusterin and Mcl-1 inhibition, enhanced mitochondrial depolarization, suppression of inhibitors of apoptosis c-IAP1, c-IAP2, XIAP and Apollon, and caspase 3/7 activation. In an in vivo model, the AZD6244/TRAIL combinatorial treatment induced highly significant growth inhibition of a TRAIL-resistant tumor associated not only with melanoma cell death, but even with suppression of pro-angiogenic molecules HIF1a, VEGFa, IL-8 and TGFb1, and with inhibition of tumor angiogenesis. These results provide a proof of principle supporting the rationale for combinatorial treatments with synergistic anti-melanoma activity based on direct and indirect anti-tumor effects.

overall_design: The human melanoma cell line Me13 was established in our laboratory from a surgical specimen. Cells were routinely maintained in RPMI medium 1640 (Lonza, Basel, Switzerland) supplemented with 10% FBS (Lonza) and 2 mM glutamine (Lonza). Cells were maintained at 37°C in a water-saturated atmosphere of 5% CO2 in air. 3x10^6 cells were seeded in 75 cm2 flasks; after 24 hours, cells were left untreated or  treated with Selumetinib (Selleck Chemicals, Houston, TX) at 0.1 micromol/L, NVP-BEZ-235 (Selleck Chemicals, Houston, TX) at 0.1 micromol/L and sTRAIL (AdipoGen) at 25ng/ml as single drugs or in combination for 8 hours. Each treatment or combination was performed in triplicate. At the end of treatment, cells were collected and RNA extracted.

first: L

first: A

last: Anichini


title: Gene expression signature in advanced colorectal cancer patients select drugs and response for the use of leucovorin, fluorouracil, and irinotecan

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

overall_design: Refer to individual Series


title: Gene expression profiles of peripheral blood mononuclear cells from HIV and HCV coinfected patients before and after 24 weeks of combined antiretroviral therapy.

city: Cincinnati

first: Rebekah

last: Karns

state: OH

address: 3333 Burnet Ave

department: Gastroenterology, Hepatology, & Nutrition

institute: Cincinnati Children's Hospital Medical Center

summary:
We aim to characterize HIV and HCV coinfected patient response to combined antiretroviral therapy through genome-wide expression profiling of patients' periperhal blood mononuclear cells before and after treatment initiation (baseline and 24 weeks).  Individuals with frank cirrhosis were excluded from the study.
We used Affymetrix PrimeView arrays to quantify baseline transcriptomic characteristics and changes in the transcriptome following treatment.  Gene expression changes were analyzed based on the change in expression of each transcript per patient.

overall_design: Mononuclear cells were purified from peripheral blood samples of 8 patients with HIV and HCV coinfection at baseline and after 24 weeks of combined antiretroviral therapy. Genes from whole blood RNA was measured via Affymetrix PrimeView microarrays.

first: Kenneth

middle: E

last: Sherman

first: Bruce

middle: J

last: Aronow


title: Genome-wide analysis of the effect of knockdown of the nuclear poly(A) binding proteins, PABPN1 and ZC3H14 on steady-state mRNA levels

status: Public on Oct 06 2014

city: Atlanta

first: Callie

last: Wigington

state: GA

address: 1510 Clifton Road RRC 4158

department: Biochemistry

institute: Emory University

summary: The polyadenosine RNA binding proteins (Pabs) represent one class of RNA binding proteins that play critical roles in gene expression. This class includes the well-studied nuclear and cytoplasmic Pabs, PABPN1 and PABPC1, respectively, as well as the newly characterized nuclear Pab, zinc finger CCCH-type containing #14, or ZC3H14. ZC3H14 was recently linked to a form of intellectual disability, suggesting a critical role for ZC3H14 in neurons; however, the post-transcriptional function of ZC3H14 is unknown. In this study, we performed a microarray analysis of cells depleted of ZC3H14 or PABPN1 in MCF-7 breast cancer cells. These results revealed that PABPN1 significantly affected ~17% of expressed transcripts as compared to ZC3H14, which affected ~1% of expressed transcripts, suggesting that ZC3H14 has specific mRNA targets. The differentially expressed mRNAs identified in this analysis not only provide information about the classes and types of transcripts that are regulated by these proteins, but also represent a set of transcripts that could be directly bound by ZC3H14 and/or PABPN1.

overall_design: Total RNA isolated from MCF-7 cells treated for 48 hours with siRNA targeting PABPN1, ZC3H14 (all splice variants), or a control scramble siRNA.

middle: P

first: Laura

last: Newman

first: Anita

middle: H

last: Corbett


title: Genome-wide gene expression analysis of EGFR inhibitor erlotinib-resistant and -sensitive head and neck squamous cell carcinoma cell lines Cal-27, SCC-25, FaDu, and SQ20B

city: Iowa City

first: Aditya

last: Stanam

state: Iowa

address: 500 Newton Road

department: Pathology

institute: University of Iowa

summary: Despite the role of epidermal growth factor receptor (EGFR) signaling in head and neck squamous cell carcinoma (HNSCC) development and progression, clinical trials involving EGFR tyrosine kinase inhibitors (TKIs) have yielded poor results in HNSCC patients. Mechanisms of acquired resistance to the EGFR TKI erlotinib was investigated by developing erlotinib-resistant HNSCC cell lines (Cal-27, SCC-25, FaDu, and SQ20B) and comparing their gene expression profiles with their parental erlotinib-sensitive HNSCC cell lines using microarray analyses. Subsequent pathway and network analyses displayed a significant upregulation in immune response pathways. Role of immune/inflammatory signaling in acquired resistance to erlotinib in HNSCC was investigated.

overall_design: Total RNA was isolated from erlotinib-resistant and erlotinib-sensitive head and neck squamous cell carcinoma cell lines Cal-27, SCC-25, FaDu, and SQ20B subjected to 48 hours of 0.01% DMSO (i.e., vehicle control).

first: Laurie

middle: L

last: Homan

first: Andrean

last: Simons


title: Control of breast cancer cell migration by a p63-regulated signaling network

first: Xiaoyu

type:
Expression profiling by array
Non-coding RNA profiling by array


title: Genome-wide analysis of gene expression in human macrophages in response to infection with influenza A viruses expressing full length or truncated non-structural protein NS1.

city: Helsinki

first: Maria

last: Anastasina

address: Tukholmankatu 8

department: Institute for Molecular Medicine, Finland

country: Finland

institute: University of Helsinki

summary:
Analysis of gene expression in human macrophages infected with influenza A viruses expressing full length or truncated NS1 protein. The hypothesis tested was that C-terminal truncations of viral NS1 protein attenuate the capability of NS1 to limit activation of host antiviral and immune response genes.
Cells were infected with influenza  A/WSN/33 viruses expressing wild type NS1 protein (WSN-230), NS1 protein of 220 aa long (WSN-220) and NS1 protein of 202 aa long (WSN-202) on non-infected (Mock)

overall_design: Total RNA isolated from macrophages after 8 hours of infection with wild type or mutant influenza A virus (multiplicity of infection = 2)

first: Denis

last: Kainov


title: Genome-wide DNA methylation analysis of lung carcinoma : Gene expression data

status: Public on Oct 05 2014

city: Lund

first: Johan

last: Staaf

address: Medicon Village

country: Sweden

institute: SCIBLU - Swegene Centre for Integrative Biology at Lund University

summary: Lung cancer is the worldwide leading cause of death from cancer. DNA methylation in gene promoter regions is a major mechanism of gene expression regulation that may promote tumorigenesis.     Experimental Design  Whole-genome DNA methylation analysis using 450K Illumina BeadArrays was performed on 12 normal lung tissues and 124 tumors including 83 adenocarcinomas, 23 squamous cell carcinomas (SqCC), one adenosquamous cancer, five large cell carcinomas, nine large cell neuroendocrine carcinomas (LCNEC), and three small cell carcinomas (SCLC). Complimentary gene expression analyses was performed on 117 of the 124 tumors using Illumina HT12 V4 arrays (reported here).

overall_design: Gene expression profiling of 117 lung carcinomas using Illumina HT-12 V4 microarrays.


title: In vitro response of fibroblasts isolated from patients with RBCK1 deficiency

status: Public on Oct 01 2014

city: Molndal

first: Elisabeth

last: Israelsson

address: Pepparedsleden 1

department: Translational Biology

institute: AstraZeneca, IMED RIA

summary: Loss-of-expression and loss-of-function mutations in HOIL1 (RBCK1) results in disruption of the linear ubiquitination assembly complex (LUBAC). Impairment of LUBAC results in impaired NF-kB activation in response to TNF and IL-1b in fibroblastic cells, but also display enhanced pro-inflammatory responses to TNF and IL-1b in leukocytes. Autosomal recessive complete human HOIL-1/RBCK1 deficiency is a new disorder with unbalanced cellular responses to pro-inflammatory cytokines, resulting in the paradoxical association of auto-inflammation and pyogenic bacterial disease, as well as the surprising development of muscular amylopectinosis. The genome-wide gene expression analysis showed that human HOIL-1 deficiency results in impaired NF-B activation in response to TNF- and IL-1 in fibroblastic cells.

overall_design: Skin fibroblast cell lines were derived from controls (n=3), patients with deficiencies for RBCK1 (HOIL1) (n=2),  MYD88 (n=1), and NEMO (n=1). Cells were cultured for 8 or 24 hours in the presence of TNF (5ng/ml) or IL1B (5ng/ml) or left unstimulated for the same length of time.

first: Bertrand

last: Boisson

first: Carolina

last: Prando

first: Emmanuel

last: Laplantine

first: Maya

last: Chrahieb

first: Giraldina

last: Trejevo

first: Pegah

last: Gandhil

first: Zaohoui

last: Xu

first: Fanny

last: Bajolles

first: Marianne

last: Debré

first: Xavier

last: Bossuyt

first: Caroline

last: Rambaud

first: Damien

last: Bonnet

first: Pierre

last: Quartier dit Maire

first: Virginia

last: Pascual

first: Jean-Christophe

last: Fournet

last: Chaussabel

first: Anne

last: Puel

first: Alain

last: Israel

first: Jean-Laurent

last: Casanova

first: Capucine

last: Picard


title: Dysregulated Expression of Lipid Storage and Membrane Dynamics Factors  in Tia1 Knock-Out Mouse Nervous Tissue

city: Tuebingen

first: Michael

middle: H.

last: Walter

address: Calwer Str. 7

department: Department of Medical Genetics

institute: University of Tuebingen

summary: During cell stress, the transcription and translation of immediate early genes are prioritized, while most other mRNAs are stored away in stress granules or degraded in P-bodies. TIA-1 is an mRNA binding protein that needs to translocate from the nucleus to seed the formation of stress granules in the cytoplasm. Since other stress granule components such as TDP-43, FUS, ATXN2, SMN, MAPT, HNRNPA2B1 and HNRNPA1 are crucial for the motor neuron diseases ALS / SMA and for the frontotemporal dementia FTD, here we studied mouse nervous tissue to identify mRNAs with selective dependence on Tia1 deletion. Transcriptome profiling with oligonucleotide microarrays in comparison of spinal cord and cerebellum, together with independent validation in quantitative reverse transcriptase PCR and immunoblots demonstrated several strong and consistent dysregulations. In agreement with previously reported TIA1 knock-down effects, cell cycle and apoptosis regulators were affected markedly with expression changes up to 2-fold, exhibiting increased levels for Cdkn1a, Ccnf, and Tprkb versus decreased levels for Bid and Inca1 transcripts. Novel and surprisingly strong expression alterations were detected for fat storage and membrane trafficking factors, with prominent above 3-fold upregulations of Plin4, Wdfy1, Tbc1d24, and Pnpla2, versus a 0.5 -fold??  downregulation of Cntn4 transcript, encoding an axonal membrane adhesion factor with established haploinsufficiency. In comparison subtle effects on the RNA processing machinery included up to 1.2-fold upregulations of Dcp1b and Tial1. The effect on lipid dynamics factors is noteworthy, since also the gene deletion of Tardbp (encoding TDP-43) and Atxn2 led to fat metabolism phenotypes in mouse. In conclusion, genetic ablation of the stress granule nucleator TIA-1 has a novel major effect on mRNAs encoding lipid homeostasis factors in the brain.

overall_design: Factorial design comparing Tia1 knock-out mice with wild type littermates in four different tissues (midbrain, cerebellum, liver, spinal cord)  and 2 different ages.

first: M

last: Heck

last: Azizov

first: T

last: Stehning

first: N

last: Kedersha

first: G

last: Auburger


title: Gene expression profile of human dental follicle cells (hDFCs) induced by conditioned medium derived from human dental pulp cells (hDPCs-CM)

status: Public on Sep 30 2014

city: Seoul

first: Su Jin

last: Park

address: 101 Daehagro, Chongro-gu

department: Department of Oral Histology-Developmental Biology

summary: The purpose of this study was to examine the effects of hDPCs-CM on osteogenic differentiation of hDFCs and to compare gene expression in hDFCs in the presence or absence of hDPCs-CM

overall_design: Total RNAs were isolated from hDFCs in osteogenic medium for 7 days with or without hDPCs-CM.

first: Su

first: Joo


title: Expression data from wild type and CBP/p300 null MEFs +/- 3hr treatment with 100uM dipyridyl (DP)

status: Public on Sep 29 2014

city: Memphis

first: Suzanne

last: Baker

state: TN

address: 262 Danny Thomas Place

department: Developmental Neurobiology

institute: St Jude Children's Research Hospital

summary: Genome-wide distribution of histone H3K18 and H3K27 acetyltransferases, Crebbp (CBP) and Ep300 (p300), is used to map enhancers and promoters, but whether these elements functionally require CBP/p300 remains largely uncertain.  We investigated this relationship by comparing genomic CBP recruitment with gene expression in wild type and CBP/p300 double-knockout fibroblasts.  ChIP-seq revealed nearby CBP recruitment for 20 percent of constitutively expressed genes, but surprisingly, three-quarters of these were unaffected or slightly activated by CBP/p300 deletion. Computationally defined enhancer-promoter-units (EPUs) having a CBP peak within two kilobases of the enhancer-like element provided better predictive value, with CBP/p300 deletion attenuating expression of 40 percent of such EPU assigned constitutively expressed genes. We next examined signaling-responsive (Hypoxia Inducible Factor) gene expression and CBP recruitment, and found that 97 percent of inducible genes were within 50 kilobases of an inducible CBP peak, and 70 percent of these required CBP/p300 for full inducible expression. Unexpectedly however, most inducible CBP peaks occurred near signal-nonresponsive genes.

overall_design: 12 samples, 3 each wild type and CBP/p300 null treated for 3hrs with 100uM dipyridyl orethanol vehicle.

first: Paul

middle: K

last: Brindle

first: Lawryn

last: Kasper


title: Gene expression profiling of HOXB4-transduced murine hematopoietic stem cells

first: Geoffrey

last: Neale

department: Hartwell Center

institute: St Jude Childrens Research Hospital

summary: Overexpression of HOXB4 in hematopoietic stem cells (HSCs) leads to increased self-renewal without causing hematopoietic malignancies in transplanted mice. The molecular basis of HOXB4-mediated benign HSC expansion in vivo is not well understood. To gain further insight into the molecular events underlying HOXB4-mediated HSC expansion, we analyzed gene expression changes at multiple time points in Lin-Sca1+c-kit+ (LSK) cells from mice transplanted with bone marrow (BM) cells transduced with a MSCV-HOXB4-ires-YFP vector. A distinct HOXB4 transcriptional program was reproducibly induced and stabilized by 12 weeks after transplant. Dynamic expression changes were observed in genes critical for HSC self-renewal as well as genes involved in myeloid and B cell differentiation. Prdm16, a transcription factor associated with human acute myeloid leukemia (AML), was markedly repressed by HOXB4 but upregulated by HOXA9 and HOXA10, suggesting that Prdm16 downregulation was involved in preventing leukemia in HOXB4 transplanted mice. Functional evidence to support this mechanism was obtained by enforcing co-expression of sPrdm16 and HOXB4, which led to enhanced self-renewal, myeloid expansion, and leukemia. Altogether, these studies define the transcriptional pathways involved in HOXB4 HSC expansion in vivo and identify repression of Prdm16 transcription as a mechanism by which expanding HSCs avoid leukemic transformation.

overall_design: 5-FU treated bone marrow cells from female C57Bl/6L mice were transduced with concentrated supernatant from GPE+86-derived producer cells containing MSCV-HOXB4-ires-YFP or MSCV-ires-GFP retroviral vectors. Transduced cells were transplanted into lethally irradiated C57Bl/6L mice. HOXB4-YFP or GFP expressing LSK cells were sorted from transplanted mice at 6, 12 and 24 weeks post transplantation, of which RNA was extracted for microarray.

first: Hui

last: Yu

first: Sheng

last: Zhou

first: Brian

last: Sorrentino


title: Genes regulated by SOX4 in glioblastoma cell line

city: hangzhou

first: jie

last: liu

address: yuhangtang road 866

institute: zcni

summary:
Overexpression of SOX4 in LN229 glioblastoma cells prevents their cell cycle
We used microarrays to detail the global programme of gene expression in SOX4 overexpression LN229 cells compared with mock control LN229 cells

overall_design: SOX4 overexpression LN229 cells and and control LN229 cells were cultured in DMEM cell culture media for RNA extraction and hybridization on Affymetrix microarrays. We sought to obtain the genes regulated by SOX4 in glioblastoma cell lines.

first: Jing

last: Zhang

first: Biaoyang

last: Lin


title: Gene expression profiling in melanoma A375 cells under anchorage, suspension, and reattachment from suspension

status: Public on Sep 24 2014

city: New Taipei City

first: Shaochen

last: Lee

address: 510 Zhongzheng Rd., Xinzhuang Dist.

department: School of Medicine

country: Taiwan

institute: FuJen Catholic University

summary: Analysis of gene expression and compare the significant changed genes with associated phenotypes

overall_design: Total RNA extracted from adherent, and suspended, and reattached A375 cells

first: ShihSheng

last: Jiang

first: Shao-Chen


title: Gene expression changes upon knockdown of DEK in the U937 cell line

status: Public on Sep 26 2014

first: Carl

last: Sanden

address: BMC B13, Klinikgatan 26

department: Department of Hematology

institute: Lund University

summary: Gene expression profiling of U937 cells upon knockdown of the DEK oncogene by two different shRNAs (shDEK14 and shDEK17).

overall_design: The DEK oncogene was knocked down by shRNA to study the changes in gene expression.

last: Sandén

first: Urban

last: Gullberg


title: Effect of pioglitazone treatment on gene expression in NCI-H2347 lung cancer cells: time course experiment

status: Public on Sep 25 2014

first: Ralf

last: Kittler

address: 5323 Harry Hines Blvd

institute: University of Texas Southwestern Medical Center

summary: Microarray studies was performed to analyze gene expression changes in NCI-H2347 cells after treatment with 50 µM  pioglitazone for 12hr, 24hr and 48hrs.

overall_design: RNA samples, containing 3 replicates for each sample, were extracted from NCI-H2347 cells after treatment with pioglitazone or vhicle (DMSO)  for 12hr, 24hr and 48hrs. After biotin labeling, samples were hybridized on the Illumina Human HT12v4.0 Expression Beadchip.

first: Nishi

last: Srivastava

first: Rahul

last: Kollipara


title: Generation of functional human pancreatic beta cells in vitro

city: Cambridge

first: Jeffrey

middle: Robert

last: Millman

state: Massachusetts

address: 7 Divinity Ave

department: HSCRB

institute: Harvard University

summary: The generation of insulin-producing pancreatic cells from stem cells in vitro would provide an unprecedented cell source for drug discovery and cell transplantation therapy in diabetes. However, insulin-producing cells previously generated from human pluripotent stem cells (hPSC) lack many functional characteristics of bona fide β cells. Here we report a scalable differentiation protocol that can generate hundreds of millions of glucose-responsive β cells from hPSC in vitro. These stem cell derived cells (SC) express markers found in mature β cells, flux Ca2+ in response to glucose, package insulin into secretory granules and secrete quantities of insulin comparable to adult β cells in response to multiple sequential glucose challenges in vitro. Furthermore, these cells secrete human insulin into the serum of mice shortly after transplantation in a glucose-regulated manner, and transplantation of these cells ameliorates hyperglycemia in diabetic mice.

overall_design: Differentiated cells were sorted and processed for RNA isolation using the MARIS protocol published previously (PMID: 24516164.)  Human embryonic stem cell (hESC) line HUES8 was differentiated into SC-beta cells. Two biological replicates were analyzed.  Those data were normalized together with and compared to existing, previously published data from Hrvatin et al. ( (PMID: 24516164) from human islet -derived insulin+ cells, undifferentiated HUES8 hES cells, and insulin+ cells derived from HUES8 cells according to previously published protocols.

first: Felicia

middle: W

last: Pagliuca

first: Mads

last: Gürtler

first: Michael

last: Segel

first: Alana

last: VanDervort

first: Jennifer

last: Ryu

first: Quinn

last: Peterson

first: Dale

last: Greiner

first: Douglas

last: Melton


title: TALEN gene knockouts reveal no requirement for the shelterin protein Rap1 in telomere protection and length regulation

city: NEW YORK

first: Shaheen

last: Kabir

state: NY

address: 1230 York Ave

institute: Rockefeller University

summary: Gene expression of human knockouts of telomere-protein Rap1 were compared to their wildtype counterparts in mutliple cell lines (available from the ATCC repository). We discovered that Rap1, desite being mostly associated with the telomere, performed a conserved role in transcriptional regulation, as evidenced by a number of genes that were differentially regulated upon deletion of Rap1.

overall_design: Total RNA was obtained from multiple knockout and wildtype clones generated in three different human parental cell lines obtained from ATCC. Datasets of multiple wild type and knockout clones were compared within cell lines, and not across cell lines, as differences in origin of cell lines led to extremely different transcriptional profiles.

first: Titia

last: de Lange


title: Gene expression data from hCdc73 knock-down HEK293 cells under confluent and sparse condition.

status: Public on Sep 23 2014

city: Pohang

first: Jay-Hyun

last: Jo

state: Gyeongbuk

address: 77 Cheongam-Ro. Nam-Gu

department: Life Science

summary: The parafibromin/hCdc73 is a component of the PAFc, which controls RNA polymerase II-mediated general transcription. In parathyroid carcinoma and familial autosomal dominant hyperparathyroidism-jaw tumor (HPT-JT), hCdc73 mutations are heavily implicated, yet the underlying mechanism of its carcinogenic action is poorly understood. Here, we demonstrate that hCdc73 specifically controls mRNA stability of p53, and p53-mediated apoptosis. hCdc73 is associated with mature p53 mRNA in the cytoplasm and facilitates its degradation. Cytoplasmic hCdc73 physically interacts with eEF1Bγ and hSki8, and this interaction is required to bind and destabilize p53 mRNA. Furthermore, enhanced association of p53 mRNA with a cancer driven hCdc73(K34Q) mutant was also observed. As a result, reduced p53 expression as well as enhanced cell proliferation was acquired in the hCdc73 (K34Q) overexpressed cells. Altogether, our findings indicate that hCdc73 directly targets p53 mRNA to repress p53 expression, and aberrant regulation of this interaction may lead to tumor progression.

overall_design: Total RNA was obtained from control siRNA or hCdc73 siRNA transfected cells, under sparse or confluent cell density condition.

first: Joo-Yeon

last: Yoo


title: Patient-based transcriptome-wide analysis identify interferon and ubiquination pathways as potential predictors of Influenza A disease severity

status: Public on Sep 28 2014

city: Singapore

first: Ahmad Nazri

last: Mohamed Naim

address: 60 Biopolis Street, Genome, #02-01

department: Infectious disease

country: Singapore

institute: Genome institute of Singapore

summary: Transcriptional profile in influenza infected patients with different clinical outcomes were investigated.

overall_design: Using gene expression profiling, we investigated the expression level of ~47,000 genes in the whole blood of patients with mild (83 patients), moderate (40 patients) and severe (11 patients) symptoms caused by influenza virus. The gene expression level in these patients was compared with febrile patients caused by unknown pathogens (73 patients)

first: Long

last: Hoang

first: Martin

last: Hibberd


title: Tsc1 promotes the differentiation of memory CD8+ T cells via orchestrating the transcriptional and metabolic programs

status: Public on Sep 20 2014

first: Geoffrey

last: Neale

summary: Memory CD8+ T cells are an essential component of protective immunity. Signaling via mechanistic target of rapamycin (mTOR) has been implicated in the regulation of the differentiation of effector and memory T cells. However, little is understood about the mechanisms that control mTOR activity, or the effector pathways regulated by mTOR, in this process. We describe here that tuberous sclerosis 1 (Tsc1), a regulator of mTOR signaling, plays a crucial role in promoting the differentiation and function of memory CD8+ T cells in response to Listeria monocytogenes infection. Mice with specific deletion of Tsc1 in antigen-experienced CD8+ T cells evoked normal effector responses, but were markedly impaired in the generation of memory T cells and their recall responses to antigen re-exposure in a cell-intrinsic manner. Tsc1 deficiency suppressed the generation of memory-precursor effector cells (MPECs) while promoting short-lived effector cell (SLEC) differentiation. Functional genomic analysis indicated that Tsc1 coordinated gene expression programs underlying immune function, transcriptional regulation and cell metabolism. Furthermore, Tsc1 deletion led to excessive mTORC1 activity and dysregulated cellular metabolism including glycolytic and oxidative metabolism. These findings establish a Tsc1-mediated checkpoint in linking immune signaling and cell metabolism to orchestrate memory CD8+ T cell development and function.

overall_design: We used microarrays to explore the gene expression profiles differentially expressed in OVA-specific CD8+ T-cells from wild-type (WT; Tsc1-fl/fl and cre-negative) and Tsc1-/- (Tsc1-fl/fl and Granzyme B-cre-positive) mice

first: Sharad

last: Shrestha

first: Kai

last: Yang

first: Hongbo

last: Chi


title: Overcoming cetuximab resistance in HNSCC: The role of AURKB and DUSP proteins

status: Public on Sep 18 2014

city: Edegem

first: Ken

last: Op de Beeck

address: Universiteitsplein 1

country: Belgium

institute: University Of Antwerp

summary: Unraveling the underlying mechanisms of cetuximab resistance in head and neck squamous cell carcinoma (HNSCC) is of major importance as many tumors remain non-responsive or become resistant. Out microarray results suggest that resistant cells still exhibit RAS-MAPK pathway signaling contributing to drug resistance, as witnessed by low expression of DUSP 5 and DUSP6, negative regulators of ERK1/2, and increased expression of AURKB, a key regulator of mitosis. Therefore, interrupting the RAS-MAPK pathway by an ERK1/2 inhibitor  (apigenin) or an AURKB inhibitor (barasertib) might be  a new strategy for overcoming cetuximab resistance in HNSCC

overall_design: 4 head and neck squamous cell carcinoma (HNSCC) cell lines were treated with either 15 nM cetuximab or PBS during 13 hours. For each cell line, differential gene expression was assessed between cetuximab and PBS treatments.

first: Carolien

last: Boeckx

first: An

last: Wouters

first: Vanessa

last: Deschoolmeester

first: Ridha

last: Limame

first: Karen

last: Zwaenepoel

first: Pol

last: Specenier

first: Patrick

last: Pauwels

first: Jan

last: Vermorken

first: Marc

last: Peeters

first: Guy

last: Van Camp

last: Baay

first: Filip

last: Lardon


title: Transcriptome data from human malanoma A375 cells stably expressing MAP4K5 shRNA.

city: Seongbuk-gu

first: Wooyoung

last: Hur

state: Seoul

address: 5 Hwarangro-14-gil, L2306

department: Chemical Kinomics Research Center

institute: Korea Institute of Science and Technology

summary: MAP4K5 is serine/threonine protein kinase similar to yeast SPS1/STE20 kinase. MAP4K5 activates JNK in mammalian cells, which suggests a role in stress response. MAP4K5 is involved in immune functions. We used microarray to investigate genome-wide transcriptional change from MAP4K5 knockdown in A375 cells.

overall_design: Total RNA's from the A375 cells where MAP4K5 was stably knocked down by shRNA were analyzed.  As a control, RNA's from A375 cells were also analyzed.

first: Taebo

last: Sim


title: HDACs and Phosphorylated Pol II CTD recruit Spt6 for cotranscriptional histone reassembly

city: Rochester

first: Chhabi

last: Govind

state: mi

address: 333 Science and Engineering Building

department: Biological Sciences

institute: Oakland University

type: Genome binding/occupancy profiling by genome tiling array

summary: Spt6 is a multifunctional histone chaperone involved in the maintenance of chromatin structure during elongation by RNA polymerase II (Pol II). Spt6 has a tandem SH2 (tSH2) domain within its C-terminus that recognizes Pol II CTD peptides phosphorylated on Ser2, Ser5 or Try1 in vitro. Deleting the tSH2 domain, however, only has a partial effect on Spt6 occupancy in vivo, suggesting that more complex mechanisms are involved in the Spt6 recruitment. Our results show that the Ser2 kinases Bur1 and Ctk1, but not the Ser5 kinase Kin28, cooperate in recruiting Spt6, genome-wide. Interestingly, the Ser2 kinases promote the association of Spt6 in early transcribed regions and not toward the 3' end of genes, where phosphorylated Ser2 reaches its maximum level. Additionally, our results uncover an unexpected role for histone deacetylases (Rpd3 and Hos2) in promoting Spt6 interaction with elongating Pol II. Finally, our data suggest that phosphorylation of the Pol II CTD on Tyr1 promotes the association of Spt6 with the 3' end of transcribed genes, independently of Ser2 phosphorylation. Collectively, our results show that a complex network of interactions, involving the Spt6 tSH2 domain, CTD phosphorylation and histone deacetylases, coordinate the recruitment of Spt6 to transcribed genes in vivo.

overall_design: We examined the genome-wide distribution (using ChIP-chip) of Spt6. Spt6 occupancy was also assayed in mutants for CTD Serine 2 and Serine 5 kinases and in mutants for histone deacetylases.  ChIPs were performed with a Myc-tagged version of Spt6. Most ChIPs (in Cy5) were hybridyzed against a control ChIP sample from an isogenic non-tagged strain (in Cy3). In the ChIP experiments with the spt6-202del mutant, non immunoprecipitated DNA (input) was used as the control. In addition to Spt6 ChIPs, the project includes RNAPII (Rpb3) ChIP-chip datasets, where an anti-Rpb3 antibody was used to ChIP RNAPII and non immunoprecipitated DNA (input) was used as the control. All ChIP-chip experiments were done in duplicates. Each microarray was normalized using the Lima Loess and replicates were combined using a weighted average method as previously described (Pokholok et al., 2005).

first: Bala

last: Burugula

first: Célia

last: Jeronimo

first: Rakesh

last: Pathak

first: Jeffery

last: Jones

first: François

last: Robert


title: Distinct genome-wide, gene-specific selectivity patterns of four glucocorticoid receptor coregulators

status: Public on Nov 30 2014

city: Los Angeles

first: Dai-Ying

last: Wu

state: CA

address: 1441 Eastlake Ave, NOR 6314

institute: University of Southern California

summary: Glucocorticoids are a class of steroid hormones that bind to and activate the Glucocorticoid Receptor, which then positively or negatively regulates transcription of many genes that govern multiple important physiological pathways such as inflammation and metabolism of glucose, fat and bone. Previous studies focusing on single coregulators demonstrated that each coregulator is required for regulation of only a subset of all the genes regulated by a steroid hormone.  We hypothesize that the gene-specific patterns of coregulators may correspond to specific physiological pathways such that different coregulators modulate the pathway-specificity of hormone action and thus provide a mechanism for fine tuning of the hormone response. Global analysis of glucocorticoid-regulated gene expression after siRNA mediated depletion of coregulators confirmed that each coregulator acted in a selective and gene-specific manner and demonstrated both positive and negative effects on glucocorticoid-regulated expression of different genes. Each coregulator supported hormonal regulation of some genes and opposed hormonal regulation of other genes (coregulator-modulated genes), blocked hormonal regulation of a second class of genes (coregulator-blocked genes), and had no effect on hormonal regulation of a third gene class (coregulator-independent genes).  In spite of previously demonstrated physical and functional interactions among these four coregulators, the majority of the several hundred modulated and blocked genes for each of the four coregulators tested were unique to that coregulator. Finally, pathway analysis on coregulator-modulated genes supported the hypothesis that individual coregulators may regulate only a subset of the many physiological pathways controlled by glucocorticoids.

overall_design: We use siRNA to deplete 4 different steroid nuclear receptor coregulators (CCAR1, CALCOCOA, CCAR2, ZNF282) in A549 cells along with nonspecific siRNA (siNS) control and assay gene expression changes 6h after hormone (100nM dexamethasone) treatment or ethanol (control) treatment.

first: Chen-Yin

last: Ou

first: Michael

middle: R

last: Stallcup


title: Expression data from transformed WT and HGPS cell lines, including HGPS cells after knock-down of BRD4

status: Public on Oct 02 2014

city: Bethesda

first: Patricia

last: Fernandez Ferri

state: MD

address: 41 Library Drive, B513

institute: NCI/NIH

summary:
Primary skin fibroblasts from a HGPS patient and an age-matched control wild-type individual were challenged in a standard transformation assay by retroviral introduction of TERT (T), V12-HRAS (R) and SV40 large and small T antigens (S). Knock-down of BRD4 in this TRS-HGPS cell line (TRS-HGPS-shBRD4) was achieved by retroviral introduction of independent shRNAs (shBRD4-1 to -3)
Abstract: Advanced age and DNA damage accumulation are strong risk factors for cancer.  The premature-aging disorder Hutchinson Gilford Progeria Syndrome (HGPS) provides a unique opportunity to study the interplay between DNA damage and aging-associated tumor mechanisms, since HGPS patients do not develop tumors despite elevated levels of DNA damage. Here, we have used HGPS patient cells to identify a protective mechanism to oncogenesis. We find that HGPS cells are resistant to neo-plastic transformation. This resistance is mediated by the bromodomain protein BRD4, which exhibits altered genome-wide binding patterns in transformation-resistant cells leading to inhibition of oncogenic de-differentiation.  BRD4 also in-hibits, albeit to a lower extent, the tumorigenic potential of transformed cells from healthy individuals and BRD4-mediated tumor protection is clinically relevant, since a BRD4 gene signature predicts positive clinical outcome in breast and lung cancer.  Our results demonstrate a protective function for BRD4 and suggest tissue-specific functions for BRD4 in tumorigenesis.

overall_design: 2 biological replicates are included for TRS-WT and TRS-HGPS cell lines. 3 biological replicates are included for TRS-HGPS-shBRD4 (derived from 3 independent shRNAs against BRD4)

last: Fernandez

first: Paola

last: Scaffidi

first: Tom

last: Misteli


title: Transcriptome analysis of fetal and adult liver samples

city: Tartu

first: Lili

last: Milani

address: Riia 23b

country: Estonia

institute: Estonian Genome Center, University of Tartu

summary: Genome wide expression analysis of 92 adult and 14 fetal liver samples

overall_design: The study includes 106 individuals, 14 fetal and 92 adult samples, no replicates. Liver samples from 14 fetuses were obtained at gestational week 8-12. Adult liver samples were collected from 50 organ donors who had met accidental death and 42 liver samples from patients undergoing liver resection due to malignant tumors, most commonly from patients with metastatic colon cancers. Liver biopsies from these patients were collected from 'healthy' tissue that showed no visible pathological changes compared to the adjacent tumor.

first: Magnus

last: Ingelman-Sundberg


title: Chronic clinical hepatic schistosomiasis japonica

status: Public on Sep 13 2014

city: Brisbane

first: Geoffrey

last: Gobert

address: 300 Herston Rd

institute: QIMR

summary: We have performed a genome wide transcriptional survey of liver biopsies obtained from patients in Hunan China, who have chronic schistosomiasis with and without past viral hepatitis history, compared to patients with no liver disease history or indicators. These results present a comprehensive transcriptional profile of chronic schistosomiasis japonica patients and demonstrate similarities and differences with other hepatic diseases. These unique features of gene expression, in conjunction with previous reports of the cellular composition of granuloma formation and recovery, present an improved understanding of the molecular immunopathology and general physiological status underlying hepatic schistosomiasis.

overall_design: The gene expression profile of the human liver was examined for chronic patients with Schistosoma japonicum infections. Microarray analysis was performed on cRNA synthesised from total RNA derived from the liver biopsy tissue from huan China. Three groups were examined based on infections status [C] were  without history or indicators of schistosomiasis or viral heapatitis controls ; [S] with a history or active for schistosomiasis but no indicators of viral heapatitis; and [S]

middle: N

first: Melissa

last: Burke

first: Donald

last: McManus

first: Yuesheng

last: Li


title: Gene expression of LY6E-silent THP-1 cells and control THP-1 cells

status: Public on Sep 06 2014

city: Cleveland

first: Xuan

last: Xu

address: 2109 Adelbert Rd

institute: Case Western Reserve University

summary: Expression profiling of LY6E-silent THP-1 cells (THP-1-shLY6E) and control cells (THP-1-shCtrl). Results provide evidence that LY6E is effectively knocked down in THP-1shLY6E, compared to THP-1-shCtrl, and show the different expressed genes following LY6E silence in THP-1 cells.

overall_design: Total RNA obtained from 2 cell lines.

first: Chan

last: Qiu

first: Jianqing


title: Multi-Omic Integrated networks connect DNA methylation and miRNA with skeletal muscle plasticity to chronic exercise in type 2 diabetic obesity [mRNA data]

status: Public on Sep 10 2014

city: Wellington

first: David

last: Rowlands

state: Wellington

address: 63 Wallace St Mt Cook

department: Institute of Food, Nutrition and Human Health

country: New Zealand

institute: Massey University

summary: Analysis of skeletal muscle gene expression from type 2 diabetic volunteers before and after 16 weeks of chronic exercise training (two groups, one undergoing aerobic ecercise and the other resistance training exercise)

overall_design: A biopsy was collected from the right Vastus Lateralis under local anaesthesia and RNA was isolated from muscle (~10 mg) using mirVana™ Kit ,  200 ng RNA from each sample was used for mRNA expression profiling using HumanHT-12_v4_BeadChip (Illumina). Arrays were scanned using HiScanSQ System. Decoded images were analyzed by GenomeStudio™ (Illumina).

first: Mamta

last: Giri


title: Addition of IL-6 inhibition to standard GVHD prophylaxis to prevent GVHD after allogeneic stem cell transplantation

status: Public on Sep 09 2014

first: Glen

middle: M

last: Boyle

state: Queensland

address: 300 Herston Road Herston

department: Department of Cell and Molecular Biology, Cancer Program

institute: QIMR Berghofer Medical Research Insitute

summary:
BACKGROUND - IL-6 mediates graft-versus-host disease (GVHD) in experimental allogeneic stem cell transplantation (alloSCT) and is an attractive therapeutic target.
METHODS - A registered phase I/II study (ACTRN12612000726853) of IL-6 receptor (IL-6R) neutralizing antibody administration on day -1 to patients receiving full or reduced-intensity conditioning (RIC) and alloSCT from HLA-matched sibling or unrelated donors with standard cyclosporin and methotrexate GVHD prophylaxis. The primary endpoint was incidence of grade II-IV acute GVHD. Outcomes were compared to a non-randomized but contemporaneous group of study patients receiving the same alloSCT in the absence of IL-6R mAb.
FINDINGS - Cytokine and pharmacokinetic analysis confirmed transient IL-6 dysregulation in the first month after alloSCT with complete inhibition following IL-6R mAb administration. With median follow up of 497 days, the incidence of grade II-IV GVHD was 12.5% in recipients of IL-6R inhibition (n = 48) versus 41.5% in the (n = 53) control cohort (P = 0.001). Low rates of acute GVHD were noted in patients receiving IL-6R inhibition relative to control patients following both myeloablative (12.5% vs. 46.4%, P = 0.03) and RIC (12.5% vs. 36.0%, P = 0.04). The incidence of severe (grade III/IV) acute GVHD was 4.2% in recipients of IL-6R inhibition versus 20.8% in the control cohort (P = 0.012). Relapse and chronic GVHD were unchanged. Immune reconstitution was preserved in recipients of IL-6R inhibition, but qualitatively modified with suppression of known pathogenic STAT3-dependent pathways.
INTERPRETATION - IL-6 is the principal detectable and dysregulated cytokine secreted after alloSCT and its inhibition is a potential new and simple strategy to protect from acute GVHD despite robust immune reconstitution and a sustained graft-versus-leukemia effect.

overall_design: Single colour, Illumina Human HT12v4 Beadarrays.

last: Kennedy

first: Antiopi

last: Varelias

first: Slavica

last: Vuckovic

first: Laetitia

last: Le Texier

first: Kate

last: Gartlan

first: Ping

last: Zhang

first: Gethin

last: Thomas

first: Nicole

last: Cloonan

first: Justine

last: Leach

first: Elise

last: Sturgeon

first: Judy

last: Avery

first: Stuart

last: Olver

first: Mary

last: Lor

first: Ashish

last: Misra

first: Cheryl

last: Hutchins

first: James

last: Morton

first: Simon

last: Durrant

first: Elango

last: Subamoniapillai

first: Jason

last: Butler

first: Cameron

last: Curley

first: Kelli

last: MacDonald

first: Siok

last: Tey

last: Hill


title: Modulation of cell metabolic pathways and oxidative stress signaling contribute to acquired melphalan resistance in multiple myeloma cells

status: Public on Sep 03 2014

city: Trondheim

first: Animesh

last: Sharma

state: Trondelag

address: Erlingskjallsons gate 1

department: Cancer Research

country: Norway

institute: NTNU

summary:
Multiple myeloma RPMI8226 cells adapted to growth in melphalan display a shift towards Warburg metabolism and modulated oxidative stress signaling
Inhibitors targeting specific enzymes in these pathways are selectively toxic to the melphalan-resistant cells.

overall_design: The gene expression profiles were measured on 6 batches each of control and melphalan-treated RPMI8226 and RPMI8226-LR5 cells using Illumina Human HT-12 v3 Expression BeadChip (Illumina, San Diego, CA), which enables genome-wide expression analysis (more than 47 000 transcripts) of 24 samples in parallel on a single microarray.

first: Kamila

last: Zub

first: Antonio

last: Sarno

first: Clifford

last: Young

first: Anders

last: Sundan

first: Ole

last: Nørregaard Jensen

first: Mirta

last: Mittelstedt

first: Leal

last: de Sousa

first: Aida

last: Demirovic

first: Shalini

last: Rao

first: Ida

last: Ericsson

first: Per

last: Aas

first: Geir

last: Slupphaug


title: Effect of PARP1 inhibition on transcription high and low PARP activity cell lines

status: Public on Sep 04 2014

city: Boston

first: Kristin

last: Krukenberg

state: MA

address: 200 Longwood Ave

department: Systems Biology

institute: Harvard Medical School

summary: Analysis of the role of PARP1 in gene transcription in cell lines with variable PARP1 activity.

overall_design: Total RNA was collected from MCF7, KPL-1, ZR7530, T47D, SKBR3, and Hs578T cells that had been treated with 10uM ABT-888 or DMSO for 48 hours.

first: Timothy

last: Mitchison


title: The effect of freeze-thaw cycles on gene expression levels in lymphoblastoid cell lines

status: Public on Sep 05 2014

city: Philadelphia

first: Minal

last: Caliskan

state: PA

address: 415 Curie Blvd., Room 540

department: Genetics

institute: University of Pennsylvania

summary: Epstein-Barr virus (EBV) transformed lymphoblastoid cell lines (LCLs) are a widely used renewable resource for functional genomic studies in humans. The ability to accumulate multidimensional data pertaining to the same individual cell lines, from complete genomic sequences to detailed gene regulatory profiles, further enhances the utility of LCLs as a model system.  However, the extent to which LCLs are a faithful model system is relatively unknown. We have previously shown that gene expression profiles of newly established LCLs maintain a strong individual component. Here, we extend our study to investigate the effect of freeze-thaw cycles on gene expression patterns in mature LCLs, especially in the context of inter-individual variation in gene regulation. We found a profound difference in the gene expression profiles of newly established and mature LCLs. Once newly established LCLs undergo a freeze-thaw cycle, the individual specific gene expression signatures become much less pronounced as the gene regulatory programs in LCLs from different individuals converge to a more uniform profile, which reflects a mature transformed B cell phenotype. As expected, previously identified eQTLs are enriched among the relatively few genes whose regulations in mature LCLs maintain marked individual signatures. We thus conclude that findings and insight drawn from gene regulatory studies in mature LCLs are generally not affected by artificial nature of the LCL model system and are likely to faithfully reflect regulatory interactions in primary tissues. However, our data indicate that many aspects of primary B cell biology cannot be observed and studied in mature LCL cultures.

overall_design: We obtained unpurified buffy coats (of a unit of blood) from six unrelated healthy individuals of Caucasian ethnicity (age range: 20-45). We isolated CD20+ B cells and established six independent cultures of LCLs between October 2009 and January 2010. From each of these samples, we obtained genome wide gene expression data using Illumina HumanHT-12 v3 Expression BeadChip arrays. We refer to data from these experiments as “cycle 0” to acknowledge the fact that the LCLs from this cycle were newly established and therefore not frozen/thawed. Between February 2011 and October 2012, we thawed each of these LCL cultures every 3 months and cultured them until obtaining ~10 million cells (February 2011=cycle 1, June 2011=cycle 2, October 2011=cycle 3, February 2012=cycle 4, June 2012=cycle 5, and October 2012=cycle 6). We used Illumina HumanHT-12 v4 Expression BeadChip arrays and obtained genome wide gene expression data on cycle 2, cycle 4 and cycle 6 LCLs. At each hybridization batch we included a subset of RNA samples that were also hybridized in a previous batch. This allowed us to effectively consider the batch effect on gene expression profiles. Our final dataset included genome wide gene expression data from 187 samples collected at 4 different time points.

first: Jonathan

last: Pritchard

first: Carole

last: Ober

first: Yoav

last: Gilad


title: Identification of CITED2 target genes in human CB

city: Groningen

first: Hein

last: Schepers

state: Groningen

address: Hanzeplein 1

department: Internal Medicine

country: Netherlands

institute: University Medical Center Groningen

summary: CB CD34+ cells were were transduced with control (tNGFR) or CITED2 overexpression lentivectors, or control (shSCR) or shRNA CITED2 lentivectors and mRNA was isolated in order to investigate global gene expression changes upon perturbation of CITED2.

overall_design: CB CD34+ cells were isolated by Miltenyi miniMACS column. Cells were prestimulated in HPGM with 100 ng/ml KITL, FLT3L and TPO for 12 hrs. Cells were transduced with control (tNGFR) or CITED2 overexpression lentivectors, or control (shSCR) shRNA CITED2 lentivectors, in three rounds over 48 hrs. Transduced cells were sorted after which RNA was isolated for Illumina beadhchip arrays HT12 v4.


title: Effect of PARP1 inhibition on transcription in MCF7 cells

summary: Analysis of the role of PARP1 in gene transcription in MCF7 cells under non-stress conditions. The hypothesis was that PARP1 activity in MCF7 cells plays a role in gene transcription. The results indicate that PARP1 inhibition does not significantly affect transcription after 6 hours of treatment.

overall_design: Total RNA was collected from MCF7 cells that had been treated with ABT-888, PJ34, Olaparib, or DMSO for 6 hours.


title: The DPY30 subunit in SET1/MLL complexes regulates the proliferation and differentiation of hematopoietic progenitor cells.

status: Public on Sep 01 2014

city: Birmingham

first: Hao

last: Jiang

state: AL

address: 1825 University Blvd

department: Biochemistry and Molecular Genetics

institute: University of Alabama at Birmingham

summary: Epigenetic mechanisms including histone modifications have emerged as important factors influencing cell fate determination. The functional role of H3K4 methylation, however, remains largely unclear in the maintenance and differentiation of hematopoietic stem/progenitor cells (HSC/HPCs). Here we show that DPY30, a shared core subunit of the SET1/MLL family methyltransferase complexes and a facilitator of their H3K4 methylation activity, is important for ex vivo proliferation and differentiation of human CD34+ HPCs. DPY30 promotes HPC proliferation by directly regulating the expression of genes critical for cell proliferation. Interestingly, while DPY30 knockdown (KD) in HPCs impaired their differentiation into the myelomonocytic lineage, it potently promoted hemoglobin production and affected the kinetics of their differentiation into the erythroid lineage. In an in vivo model, we show that morpholino-mediated dpy30 KD resulted in severe defects in the development of the zebrafish hematopoietic system, which could be partially rescued by co-injection of dpy30 mRNA. Taken together, our results establish a critical role of DPY30 in the proliferation and appropriate differentiation of hematopoietic progenitor cells as well as in animal hematopoiesis. Finally, we also demonstrate a crucial role of DPY30 in the growth of several MLL1-fusion-mediated leukemia cell lines.

overall_design: Total RNAs from control (scr) or knockdown (hD2, hD5) cells before and after culturing under condition promoting myelomonocytic differentiation were subjected to Illumina microarray analyses.


title: Mucosal transcriptomics implicates under expression of FAM5C in the pathogenesis of ulcerative colitis

city: London

first: Professor Anthony

last: Segal

address: Rayne Building, 5 University Street

department: Division of Medicine

institute: Centre for Molecular Medicine

summary: Background and aims:  Mucosal abnormalities are potentially important in the primary pathogenesis of ulcerative colitis (UC).  We investigated the mucosal transcriptomic expression profiles of biopsies from patients with UC and healthy controls (HC), taken from macroscopically non-inflamed tissue from the terminal ileum and three colonic locations with the objective of identifying abnormal molecules that might be involved in disease development.  Methods: Whole-genome transcriptional analysis was performed on intestinal biopsies taken from 24 UC, 26 HC and 14 patients with Crohn’s disease. Differential gene expression analysis was performed at each tissue location separately and results were then meta-analysed using Fisher’s method.  Significantly differentially expressed genes were validated using qPCR. Gene location within the colon was determined using immunohistochemistry, subcellular fractionation, electron and confocal microscopy. DNA methylation was quantified by pyrosequencing.  Results: Seven probes were abnormally expressed throughout the colon in UC patients with Family with sequence similarity member 5 C (FAM5C) being the most significantly underexpressed.  Attenuated expression of FAM5C in UC was independent of inflammation, unrelated to phenotype or treatment, and remained low at rebiopsy approximately 23 months later. FAM5C is localised to the brush border of the colonic epithelium and expression is influenced by DNA methylation within its promoter.  Conclusion: Genome-wide expression analysis of non-inflamed mucosal biopsies from UC patients identified FAM5C as significantly under-expressed throughout the colon in a major sub-set of patients with UC. Low levels of this gene could predispose to or contribute to the maintenance of the characteristic mucosal inflammation seen in this condition.

overall_design: Total RNA was extracted from the intestinal biopsies taken from macroscopically normal mucosa in the rectum, descending colon, ascending colon and terminal ileum in clinically quiescent Ulcerative colitis and Crohn's disease patients and compared to healthy controls. Normalized data for 26,261 probes out of 47,323 only. Criteria for inclusion not specified. The non-normalized matrix contains the complete non-normalized data for all probes.

first: Philip

last: Smith

first: Adam

last: Levine

first: Jenny

last: Dunne

first: Paul

last: Guilhamon

first: Mark

last: Turmaine

first: Gavin

last: Sewell

first: Roser

last: Vega

first: Nuala

last: O'Shea

first: Jennifer

last: Paterson

first: Dahmane

last: Oukrif

first: Stephan

last: Beck

first: Stuart

last: Bloom

first: Marco

last: Novelli

first: Manuel

last: Rodriguez-Justo

first: Andrew

first: Anthony


title: A newly identified spliced isoform of metadherin differently regulates the global transcriptomic profile in MDA-MB-231 breast cancer cells

city: Hyderabad

first: Srigiridhar

last: Kotamraju

state: Andhrapradesh

address: Uppal road

department: Centre for Chemical Biology

country: India

institute: CSIR-Indian Institute of Chemical Technology

summary: The current study analyzed the metadherin (MTDH)-mediated altered gene expression profiles in ER negative MDA-MB-231 cells. Some of these altered gene expressions were further inter connected to various pathways which may eventually be recognized as drug targets or biomarkers in those breast cancers where MTDH plays a role in cancer progression/metastasis.

overall_design: To understand the global differential gene expression profile in MTDH-wild type and a newly identified MTDH-isoform knock down in metastatic breast cancer cells. This data was compared to untreated breast cancer cells.

first: Paradesi

last: Gollavilli

first: Anantha

last: Kanugula

first: Sandhya

last: Pemmasani


title: Genome-wide analysis of gene expression by SCTR siRNA transfection in breast cell line MCF-10A

status: Public on Aug 27 2014

city: Seoul

first: Sun Jung

last: Kim

address: Pil-dong 3-ga, Jung-gu

country: South Korea

institute: Dongguk university

summary: Analysis of tumor suppression by cell cycle-related genes which are regulated by SCTR(Secretin receptor) at gene expression level. The hypothesis tested in the present study was that SCTR regulates cell cycle-related genes toward tumor suppression in normal breast cells. Results suggest that normal breast cells have tumor suppressor activity when SCTR was knocked down by siRNA.

overall_design: Total RNA obtained from  MCF-10A where SCTR was knocked down by siRNA

first: Seongeun

last: Kang

first: Sun


title: A newly identified spliced isoform of metadherin differently regulates the global transcriptomic profile in human breast cancer cells

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

overall_design: Refer to individual Series


title: A newly identified spliced isoform of metadherin differently regulates the global transcriptomic profile in MCF-7 breast cancer cells

summary: The current study analyzed the metadherin (MTDH)-mediated altered gene expression profiles in ER positive MCF-7 cells. Some of these altered gene expressions were further inter connected to various pathways which may eventually be recognized as drug targets or biomarkers in those breast cancers where MTDH plays a role in cancer progression/metastasis.

overall_design: To understand the global differential gene expression profile in MTDH-wild type and a newly identified MTDH-isoform knock down in malignant breast cancer cells. This data was compared to untreated breast cancer cells.


title: Fluvastatin-induced differential global gene expression in human malignant MCF-7 breast cancer cells

summary: The current study analyzed the altered expression profiles of genes that are responsible for fluvastatin-induced breast cancer cell death in MCF-7 cells (ER+ve luminal breast cancer cells). Some of these altered gene expressions were further inter connceted to various pathways which may eventually be recognised as drug targets/ biomarkers in statin-sensitve breast cancer patients.

overall_design: To understand the differential gene expression profile in fluvastatin treated (24 h) malignant breast cancer cells with untreated malignant breast cancer cells.


title: The effect of TRPM2-AS depletion in human prostate carcinoma PC3 cell line

city: Milano

first: Giovanni

last: Lavorgna

address: Via Olgettina, 60

country: Italy

institute: Ospedale San Raffaele

summary: There is overwhelming evidence indicating that human cancer is a genetic disease caused by sequential accumulation of mutations in oncogenes and tumor suppressor genes. However, it is also increasingly apparent that cancer depends not only on mutations in these coding genes, but also on alterations in the large class of the non-coding RNAs (ncRNAs). Here, we report that one such long ncRNA, TRPM2-AS, an antisense transcript in respect to TRPM2, a gene encoding for a ion channel activated by oxidative stress, is significantly overexpressed in prostate cancer. High expression levels of either TRPM2-AS or of a related gene signature are linked to poor clinical outcome, with the related gene signature working also independently of the patient's Gleason score. Moreover, TRPM2-AS knock-out leads to apoptosis of prostate cancer cells, with transcriptional profiling indicating an unbearable increase of cellular stress in dying cells, coupled to the down-regulation of several already known oncological targets. Considering that TRPM2-AS transcripts are barely detectable in healthy cells, these data strongly suggest that it, beside being a novel prognostic marker, is also a suitable therapeutic target in prostate cancer and establish a strong rationale for developing agents targeting either its expression or the expression of molecules in its pathway.

overall_design: PC3 cells were transfeted  either a non-specific siRNA or with a TRPM2-AS siRNA in replicates. Cells were grown for 48 hours, then were harvested and RNA was isolated


title: Fluvastatin mediated global transcriptional alterations in estrogen  positive and negative human breast cancer cells


title: Gene Expression Profiling in Polycythemia Vera (PV)

status: Public on Aug 29 2014

city: Baltimore

first: Jerry

middle: L.

last: Spivak

address: 720 Rutland Avenue

department: Medicine

institute: Johns Hopkins University

summary: To define the molecular abnormalities at the stem cell level in polycythemia vera (PV), we examined global gene expression in circulating CD34+ cells from 19 JAK2 V617F-positive PV patients and 6 normal individuals using Affymetrix oligonucleotide microarray technology. We observed that CD34+ cell gene expression not only differed between the PV patients and the normal controls but also between men and women PV patients. Based on these gender-specific differences in gene expression, we were able to identify 102 genes differentially regulated concordantly by both men and women, which likely represent a core set of genes whose dysregulation is involved in the pathogenesis of PV. Gene expression was verified by Q-PCR of patient CD34+ cell RNA. Using the 102 gene set and unsupervised hierarchical clustering, the 19 PV patients could be separated in two groups that differed significantly with respect to hemoglobin level, thrombosis frequency, splenomegaly, splenectomy or chemotherapy exposure, leukemic transformation and overall survival. These results were confirmed using top scoring pairs, which identified a different set of 29 genes that independently segregated the 19 patients into the same two clinical groups: those with an aggressive form of the disease (7 patients), and those with an indolent form (12 patients).

overall_design: Samples from 19 PV patients (8 men and 11 women) and 6 normal controls (3 men and 3 women) were analyzed using Affymetrix oligonucleotide microarray U133A.


title: Fluvastatin-induced differential global gene expression in human metastatic MDA-MB-231 breast cancer cells

summary: The current study analyzed the altered expression profiles of genes that are responsible for fluvastatin-induced breast cancer cell death in MDA-MB-231 cells (ER-ve basal breast cancer cells). Some of these altered gene expressions were further inter connceted to various pathways which may eventually be recognised as drug targets/ biomarkers in statin-sensitve breast cancer patients.


title: Transcription profiling by array of epidermal shave samples taken from lesional and non-lesional skin from German atopic dermatitis patients and from healthy skin from German controls

status: Public on Aug 26 2014

city: Kiel

first: Hansjoerg

last: Baurecht

address: Schittenhelmstr. 7

department: Department of Dermatology, Venereology and Allergology

country: Germany

institute: University Hospital Schleswig-Holstein, Campus Kiel

summary: Epigenetic alterations are increasingly recognized as mechanisms for disease-associated changes in genome function and important risk factors for complex diseases. The epigenome differs between cell types and so far has been characterized in few human tissues only. In order to identify disease-associated DNA methylation differences for atopic dermatitis (AD), we investigated DNA from whole blood, T cells, B cells, as well as lesional and non-lesional epidermis from AD patients and healthy controls. To elicit functional links, we examined epidermal mRNA expression profiles. No genome-wide significant DNA methylation differences between AD cases and controls were observed in whole blood, T cells, and B cells, and, in general, intra-individual differences in DNA methylation were larger than interindividual differences. However, striking methylation differences were observed between lesional epidermis from patients and healthy control epidermis for various CpG sites, which partly correlated with altered transcript levels of genes predominantly relevant for epidermal differentiation and innate immune response. Significant DNA methylation differences were discordant in skin and blood samples, suggesting that blood is not an ideal surrogate for skin tissue. Our pilot study provides preliminary evidence for functionally relevant DNA methylation differences associated with AD, particularly in the epidermis, and represents a starting point for future investigations of epigenetic mechanisms in AD.

overall_design: Total RNA obtained from 7 patients from non-lesional skin, 12 patients from lesional skin and 14 controls from healthy skin

first: Elke

last: Rodríguez

first: Hansjörg

first: Anna

middle: F

last: Wahn

first: Anja

last: Kretschmer

first: Melanie

last: Hotze

first: Sonja

last: Zeilinger

first: Norman

last: Klopp

first: Thomas

last: Illig

first: Katharina

last: Schramm

first: Holger

last: Prokisch

first: Brigitte

last: Kühnel

first: Christian

last: Gieger

first: Jürgen

last: Harder

first: Liliana

last: Cifuentes

first: Natalija

last: Novak

last: Weidinger


title: Expression data from activated and non-activated NTAL knockout, wild type and knockdown bone marrow derived mast cells

city: Prague

first: Iva

last: Polakovicova

address: Videnska 1083

country: Czech Republic

institute: Institute of Molecular Genetics ASCR

summary: Non-T cell activation linker (NTAL, also called Lab or LAT2) is a transmembrane adaptor protein involved in the high affinity IgE receptor (FcεRI) signaling in mast cells. Studies with bone marrow-derived mast cells (BMMCs) from NTAL-/- mice indicated that NTAL is a negative regulator of FcεRI signaling. In contrast, depletion of NTAL by RNA interference in human or rat mast cells suggested its positive regulatory role. To determine whether compensatory developmental alterations are responsible for the observed discrepancies, we compared FcεRI-mediated signaling events in BMMCs isolated from NTAL-/- mice or BMMCs of wild type in which NTAL expression was decreased by RNA interference. We found that when compared to corresponding controls, NTAL-deficient cells, both knockouts (KOs) and knockdowns (KDs), exhibited enhanced degranulation, calcium mobilization, tyrosine phosphorylation of linker for activation of T cells (LAT) and ERK, depolymerization of filamentous actin and chemotaxis. These data indicate that NTAL in mouse BMMCs is a negative regulator of FcεRI signaling, independently of compensatory developmental alterations. To gain more insight into NTAL function, we examined gene expression profiles of resting and antigen-activated BMMCs with NTAL KO or KD and corresponding controls and identified several genes that were more than 1.8-fold differentially expressed in resting and FcεRI-activated NTAL-deficient cells, when compared to wild-type controls. We provide evidence that at least some of these genes could be involved in regulation of cholesterol-dependent events in chemotaxis towards antigen.

overall_design: Two types of NTAL-deficient bone marrow derived mast cells (BMMCs) were used (1) cells isolated from NTAL KO mice and (2) NTAL KD cells prepared by lentiviral infection of  the NTAL shRNA into WT cells. Activated and nonactivated NTAL-deficient mast cells were compared with the WT cells and the WT cells infected with the empty vector pLKO.1 used as a negative control to  NTAL KDs. Three biological replicates of each sample were analyzed. One of the 24 samples, KO 2_2 h, failed during processing  and was removed.

first: Petr

last: Draber


title: Clear cell sarcoma of the kidney demonstrates an embryonic signature indicative of a primitive nephrogenic origin

status: Public on Aug 22 2014

city: Lund

first: Jenny

last: Karlsson

address: BMC C13

department: Clinical genetics

institute: Lund University

summary: Gene expression profiling of CCSK in comparison with non-neoplastic foetal and adult kidney

overall_design: Total RNA extracted from 22 frozen CCSKs and 6 adult non-neoplastic kidneys and comercially obtained  RNA from 4 foetal kidneys, were hybridized to Illumina humanHT-12 v4.0 Expression BeadChip at the SCIBLU Lund University Sweden (http://www.lth.se/sciblu).

first: Linda

last: Holmquist Mengelbier

first: Cristina

middle: D

last: Ciornei

first: Arlene

last: Naranjo

first: Maureen

last: O’Sullivan

first: David

last: Gisselsson


title: Cell-Independent MicroRNA Biogenesis

city: Houston

first: RAGHU

last: KALLURI

address: 1881 East Rd.

department: CANCER BIOLOGY

country: USA

institute: MDACC

sample_organism:
Homo sapiens
Mus musculus

platform_organism:
Homo sapiens
synthetic construct


title: TUSC4 functions as a tumor suppressor by regulating BRCA1’s stability via the E3 ubiquitination pathway

status: Public on Aug 21 2014

first: Yang

last: Peng

state: TEXAS

address: 7435 Fannin Street

institute: MD Anderson Cancer Center

summary: Expression of the tumor suppressor protein BRCA1 is frequently lost in breast cancer patients, and the loss of its expression is associated with disruption of various critical functions in cells and cancer development. In the present study, we demonstrated that microarray analysis of cells with tumor suppressor candidate 4 (TUSC4) knockdown indicated critical changes such as cell cycle, cell death pathways and a global impact to cancer development. More importantly, we observed a clear cluster pattern of TUSC4-knockdown gene profiles with established homologous recombination (HR) repair defect signature. Additionally, TUSC4 protein can physically interact with E3 ligase Herc2 and prevents BRCA1 degradation via ubiquitination pathway. Knockdown of TUSC4 expression enhanced BRCA1 polyubiquitination, leading to BRCA1 protein degradation and a marked reduction in HR repair efficiency. Notably, ectopic expression of TUSC4 effectively suppressed the proliferation, invasion, and colony formation of breast cancer cells in vitro and tumorigenesis in vivo. Furthermore, knockdown of TUSC4 expression transformed normal mammary epithelial cells and enhanced the sensitivity of U2OS cells to the treatment of poly(ADP-ribose) polymerase inhibitors. Therefore, TUSC4 may act as a bona fide tumor suppressor by regulating BRCA1 protein stability and function in breast cancer.

overall_design: Two groups of samples are included: 1.U2OS-shcontrol 2.U2OS-shTUSC4 knockdown. Gene expression profiles of U2OS-shTUSC4  cells were compared to that of parental U2OS-shcontrol cells.

first: Hui

last: Dai

first: Edward

last: Wang

first: Curtis

last: Lin

first: Wei

last: Mo

first: Guang

first: Shiaw-Yih


title: Molecular subtyping of serous ovarian tumors reveals multiple connections to intrinsic breast cancer subtypes

status: Public on Aug 15 2014

first: Jenny-Maria

last: Jönsson

address: Scheelevägen 2

department: Division of Oncology, Department of Clinical Sciences

summary: Epithelial ovarian cancer is morphologically and clinically heterogeneous. Transcriptional profiling has revealed molecular subtypes (referred to as “C-signatures”) that correlate to biological as well as clinical features. We aimed to determine gene expression differences between malignant, benign and borderline serous ovarian tumors, and to investigate similarities to the intrinsic molecular subtypes of breast cancer. Global gene expression profiling was performed using Illumina's HT12 Bead Arrays and applied to 59 fresh-frozen ovarian tumors. SAM analysis revealed enrichment of cell cycel processes among the malignant tumors, in line with malignant tumors being highly proliferative. The borderline tumors were split between the malignant and benign tumor clusters, indicating that borderline tumors have both malignant and benign features. Furthermore, nearest centroid classification was performed applying previously published gene profiles for the ovarian cancer C-signatures and the intrinsic breast cancer subtypes, respectively, and showed significant correlations between the malignant serous tumors and the highly aggressive C1, C2  and C4 ovarian cancer signatures, and the basal-like breast cancer subtype. The benign and borderline serous tumors together were significantly correlated to the normal-like breast cancer subtype and the ovarian cancer C3 signature. The borderline tumors, on the other hand, correlated significantly to the Luminal A breast cancer subtype. These findings remained when analyzed in a large, independent dataset. The data in this study link the transcriptional profiles of serous ovarian cancer to the intrinsic molecular subtypes of breast cancer, in line with the shared clinical and molecular features between high-grade serous ovarian cancer and basal-like breast cancer, including an aggressive phenotype, frequent TP53 mutations and a high degree of genomic instability, and suggest that biomarkers and targeted therapies may overlap between these subsets of ovarian and breast cancers.  Finally, the link between benign and borderline ovarian cancer and luminal breast cancer may indicate endocrine responsiveness in a subset of ovarian cancers.

overall_design: Total RNA obtained from serous ovarian adenocarcinomas, adenomas and borderline tumors. Gene expression profiling using Illumina's HT12 v4 bead arrays. Application of ovarian cancer molecular subtypes and intrinsic breast cancer subtypes using nearest centroid classification. KRAS and BRAF mutation analyses in the malignant and borderline tumors.

first: Ida

last: Johansson

first: Mev

last: Dominguez-Valentin

first: Siker

last: Kimbung

first: Mats

first: Jesper

last: Bonde

first: Anna

last: Måsbäck

first: Susanne

last: Malander

first: Mef

last: Nilbert

first: Ingrid

last: Hedenfalk


title: Genetic Neuropathology of Obsessive Psychiatric Syndromes

status: Public on Aug 08 2014

first: Andrew

last: Jaffe

address: 855 N Wolfe St, Ste 300

department: Clinical Sciences

institute: Lieber Institute for Brain Development

summary: Anorexia nervosa (AN), bulimia nervosa (BN), and obsessive-compulsive disorder (OCD) are complex psychiatric disorders with shared obsessive features, thought to arise from the interaction of multiple genes of small effect with environmental factors.  Potential candidate genes for AN, BN, and OCD have been identified through clinical association and neuroimaging studies; however, recent genome-wide association studies of eating disorders (ED) so far have failed to report significant findings. Additionally, few if any studies have interrogated postmortem brain tissue for evidence of eQTLs associated with candidate genes, which has particular promise as an approach to elucidating molecular mechanisms of association. We therefore selected single nucleotide polymorphisms (SNPs) based on candidate gene studies for AN, BN, and OCD from the literature, and examined the association of these SNPs with gene expression across the lifespan in prefrontal cortex of a non-psychiatric control cohort (N=268).   Several risk-predisposing SNPs were significantly associated with gene expression among control subjects. We then measured gene expression in the prefrontal cortex of cases previously diagnosed with obsessive psychiatric disorders, e.g., eating disorders (ED; N=15), and obsessive-compulsive disorder/obsessive-compulsive personality disorder or tics (OCD/OCPD/Tic; N=16), and non-psychiatric controls (N=102) and identified 6 and 286 genes that were differentially expressed between ED compared to controls and OCD cases compared to controls, respectively (FDR < 5%). However, none of the clinical risk SNPs were among the eQTLs and none were significantly associated with gene expression within the broad obsessive cohort, suggesting larger sample sizes or other brain regions may be required to identify candidate molecular mechanisms of clinical association in postmortem brain datasets.

overall_design: Gene expression data from the dorsolateral prefrontal cortex (DLPFC) from postmortem tissue on 133 subjects - 15 eating disorder (ED) patients, 16 obessive compulsive disorder (OCD) patients, and 102 non-psychiatric controls - run on the Illumina HumanHT-12 v3 microarray


title: Toxicology study on KhES-3 cells.

status: Public on Aug 07 2014

city: Kyoto

first: Wataru

last: Fujibuchi

address: 53 Kawahara-cho, Shogoin, Sakyo-ku

country: Japan

institute: Kyoto University

summary: Perform microarray study to select sensitive genes for toxicology analysis on hESC validation system.

overall_design: 10 different toxic chemicals at 48h and 2 controls at 0h and 48h are used

first: Junko

last: Yamane

first: Satoshi

last: Imanishi

first: Hiromi

last: Akanuma

first: Reiko

last: Nagano

first: Hideko

last: Sone

first: Seiichiro

last: Ohsako


title: Systems Analysis of a RIG-I Agonist Inducing Broad Spectrum Inhibition of Virus Infectivity

city: Port Saint Lucie

first: John

last: Hiscott

state: Florida

address: 9801 SW Discovery Way

department: Infectious Diseases

institute: Vaccine and Gene Institute-Florida


title: Systems Analysis of a RIG-I Agonist Inducing Broad Spectrum Inhibition of Virus Infectivity [comparison]

summary: The RIG-I like receptor pathway is stimulated during RNA virus infection by interaction between cytosolic RIG-I and viral RNA structures that contain short hairpin dsRNA and 5’ triphosphate (5’ppp) terminal structure. In the present study, an RNA agonist of RIG-I was synthesized in vitro and shown to stimulate RIG-I-dependent antiviral responses at concentrations in the picomolar range. In human lung epithelial A549 cells, 5’pppRNA specifically stimulated multiple parameters of the innate antiviral response, including IRF3, IRF7 and STAT1 activation, andinduction of inflammatory and interferon stimulated genes - hallmarks of a fully functional antiviral response. Evaluation of the magnitude and duration of gene expression by transcriptional profiling identified a robust, sustained and diversified antiviral and inflammatory response characterized by enhanced pathogen recognition and interferon (IFN)signaling. Bioinformatics analysis further identified a transcriptional signature uniquely induced by 5’pppRNA, and not by IFNα-2bthat included a constellation of IRF7 and NF-kB target genes capable of mobilizing multiple arms of the innate and adaptive immune response. Treatment of primary PBMCs or lung epithelial A549 cells with 5’pppRNA provided significant protection against a spectrum of RNA and DNA viruses. In C57Bl/6 mice, intravenous administration of 5’pppRNA protected animals from a lethal challenge with H1N1 Influenza, reduced virus titers in mouse lungs and protected animals from virus-induced pneumonia. Strikingly, the RIG-I-specific transcriptional response afforded partial protection from influenza challenge, even in the absence of type I interferon signaling. This systems approach providestranscriptional, biochemical, and in vivo analysis of the antiviral efficacy of 5’pppRNA and highlights the therapeutic potential associated with the use of RIG-I agonists as broad spectrum antiviral agents.

overall_design: A549 cells were either non-treated, treated with RNAiMax only, transfected with 5'pppRNA, or treated with IFNa-2b and analysed at 6h or 24h.

first: Marie-Line

last: Goulet

first: David

last: Olagnier

first: Zhengyun

last: Xu

first: Suzanne

last: Paz

first: S

last: Belgnaoui

first: Erin

middle: I

last: Lafferty

first: Valérie

last: Janelle

first: Meztli

last: Arguello

first: Marilene

last: Paquet

first: Khader

last: Ghneim

first: Stephanie

last: Richards

last: Smith

first: Peter

last: Wilkinson

first: Mark

last: Cameron

first: Ulrich

last: Kalinke

first: Salman

last: Qureshi

first: Alain

last: Lamarre

first: Elias

last: Haddad

first: Rafick

last: Sekaly

first: Suraj

last: Peri

first: Siddharth

last: Balachandran

first: Rongtuan

last: Lin