title: IL-17 mediates susceptibility to breast cancer growth by promoting the recruitment of tumorigenic neutrophils

status: Public on Apr 01 2015

city: Toronto

first: Daniel

last: De Carvalho

state: ON

address: 101 College Street, room 9-302

country: Canada

institute: Ontario Cancer Institute

summary: The aggressiveness of invasive ductal carcinoma (IDC) of the breast is associated with increased IL-17 levels. In this study, we investigated the role of IL-17 in invasive breast tumor pathogenesis. We found that metastatic tumor-infiltrating T lymphocytes produced elevated levels of IL-17, whereas IL-17 neutralization inhibited tumor growth and prevented the migration of neutrophils and tumor cells to secondary disease sites. Tumorigenic neutrophils promote disease progression, and their depletion suppressed tumor growth. Moreover, IL-17 induced IL-6 and CXCL1 production in tumor cells, and IL-6 depletion reduced metastatic tumor growth and infiltration by Th17 cells and neutrophils. In addition, inoculation of a non-metastatic mammary tumor cell line pre-incubated with IL-17 promoted tumor growth, confirming the pro-tumor role of IL-17. Furthermore, high IL-17 expression was associated with lower disease-free survival (DFS) and worse prognosis in IDC patients. Thus, IL-17 blockade represents an attractive approach for the control of invasive breast tumors.

overall_design: Biopsies of patients with breast tumors

first: D

first: L

last: Benevides


title: Human basophil expression profiles (in vitro) (Ref 8)

status: Public on Mar 20 2015

city: Baltimore

first: Donald

middle: Welton

last: MacGlashan

state: MD

address: 5501 Hopkins Bayview Circle

department: Allergy and Clinical Immunology

country: USA

institute: Johns Hopkins University

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

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


title: A novel functional role for the serine protease inhibitor SerpinA3N and its substrate leukocyte elastase in neuropathic pain

status: Public on Feb 19 2015

city: Boston

first: Michael

last: Costigan

state: MA

address: CLS 12

department: Neurology

institute: Boston Children's Hospital

summary: Two out-bred rat selection lines were separated to produce different hypersensitivity phenotypes following nerve injury. These lines were termed High Pain and Low Pain (HP or LP). Each sub-strain was either subject to a Sham surgery or a Spinal Nerve Ligation (SNL) surgery to the L4 and L5 spinal nerves. Three days following surgery L4/L5 Dorsal Root Ganglia (DRG) were dissected from these animals. For the rat line separation protocol see: Devor M, Raber P (1990) Heritability of symptoms in an experimental model of neuropathic pain. Pain 42:51-67.

overall_design: 12 Hybridizations, 3 per condition; Sham HP DRG; 3 day SNL HP DRG; Sham LP DRG; 3 day SNL LP DRG.

first: Robert

middle: S

last: Griffin


title: A vlincRNA participates in senescence maintenance by relieving H2AZ mediated repression at the INK4 locus

status: Public on Jan 20 2015

city: Toulouse

first: Estelle

last: Nicolas

address: 118 route de Narbonne

country: France

institute: INSERM

type: Expression profiling by genome tiling array

summary: Non-coding RNAs (ncRNAs) play major roles in proper chromatin organization and function. Senescence, a strong anti-proliferative process and a major anti-cancer barrier, is associated with dramatic chromatin reorganization in heterochromatin foci. Here, we analyze strand-specific transcriptome changes during oncogene-induced human senescence. Strikingly, while differentially-expressed RNAs are mostly repressed during senescence, ncRNAs belonging to the recently described vlincRNA (very long intergenic ncRNA) class are mainly activated.  We show that VAD, a novel antisense vlincRNA  strongly induced during senescence, is required for the maintenance of senescence features. VAD modulates chromatin structure in cis and activates gene expression in trans at the INK4 locus which encodes cell cycle inhibitors important for senescence-associated cell proliferation arrest. Importantly, VAD inhibits the incorporation of the repressive histone variant H2A.Z at INK4 gene promoters in senescent cells. Our data underline the importance of vlincRNAs as sensors of cellular environment changes and as mediators of the correct transcriptional response.

overall_design: 2 samples were analyzed: cont (total RNA from WI38 hTERT RAF1-ER in proliferation) and sen (total RNA from WI38 hTERT RAF1-ER in senescence) in duplicates (2 different experiments)

first: Sandra

last: Lazorthes

first: Céline

last: Vallot

first: Sébastien

last: Briois

first: Marion

last: Aguirrebengoa

first: Jean-Yves

last: Thuret

first: Georges

first: Claire

last: Rougeulle

first: Philipp

last: Kaparanov

first: Carl

last: Mann

first: Didier

last: Trouche


title: Twinfilin regulates breast cancer cell invasion and interleukin-11 expression through the miR-206/ MKL1/SRF pathway

status: Public on Dec 31 2014

city: Chapel Hill

first: Charles

middle: M.

last: Perou

state: NC

address: 12-044 Lineberger Comprehensive Cancer Center CB# 7295

department: Professor of Genetics, and Pathology & Laboratory Medicine; Lineberger Comprehensive Cancer Center

institute: University of North Carolina at Chapel Hill

summary: Recent studies have implicated genes that control actin cytoskeleton dynamics as important regulators in cellular invasion, a critical step in metastasis. Many of their downstream pathways still remain to be discovered. MicroRNAs have emerged as important epigenetics regulators of important cellular processes and aid in the identification of pathways involved in breast cancer progression and metastasis. In this study, we characterized the miR-206 downstream pathway specifically its direct target, Twinfilin (TWF1), a g-actin regulator and their downstream target, interleukin-11 (IL-11). We determined that miR-206 and TWF1 regulate IL-11 expression through the mycocardian-related transcription factor (MRTF-A or MKL1) and serum response factor (SRF) complex. Identification of this novel pathway that regulates breast cancer invasion will aid in the understanding of metastasis and development of new treatment strategies.

overall_design: reference x sample

first: Ravand

last: Samaeekia

first: Jessica

last: Bockhorn

middle: M

first: Huiping

last: Liu


title: Genome wide analysis of copy number variation in NAFLD spectrum

status: Public on Feb 26 2015

city: kuala lumpur

first: shamsul mohd

last: zain

address: jalan lembah pantai

department: department of pharmacology

country: Malaysia

institute: univeristy of malaya

type: Genome variation profiling by genome tiling array

summary: Despite some success in identifying CNVs responsible for metabolic phenotypes including obesity and diabetes mellitus, there are as yet no data available to suggest whether or not CNVs might be involved in the etiology of the NAFLD spectrum. This report is a comprehensive analysis of copy number in Malaysian patients with NAFLD.

overall_design: Genomic DNA was extracted from blood obtained from patients with NAFLD and submitted for genome-wide analysis using aCGH

first: S

last: Zain

first: Z

last: Mohamed


title: Global gene expression of nasal epithelial cells in patients with seasonal allergic rhinitis

status: Public on Jan 16 2015

city: Tsukuba

first: Emiko

last: Noguchi

address: 1-1-1 Tennoudai

country: Japan

institute: University of Tsukuba

summary:
Analysis of nasal epithelial cells from adult patients with seasonal allergic rhinitis and from non allergic controls.
Results provide insight into the molecular mechanisms associated with inflammatory responses in nasal mucosa.

overall_design: Total RNA was obtained from nasal epithelial cells of 7 seasonal allergic rhinitis patients and 5 non-allergic control subjects


title: Genome-wide analysis of gene expression altered by KLRK1 (NKG2D) ectopically expressed  in MCF-7 breast cancer cells

city: Seattle

first: Xin

last: Cai

state: WA

address: 1100 Fairview Ave N

department: Clinical Research Division

institute: FHCRC

summary: KLRK1 induces expression of Sox9

overall_design: Total RNA from MCF-7 cells expressing NKG2D (MCF-7-TF) and mock-transfected negative control

first: Veronika

last: Spies

first: Thomas

first: Jeff

last: Delrow

first: Alyssa

middle: D

last: Dawson


title: The genetics of splicing in neuroblastoma

status: Public on Apr 03 2015

city: San Francisco

first: William

middle: A.

last: Weiss

state: CA

address: 1450 3rd Street, HD-220

institute: University of California, San Francisco

summary: Regulation of mRNA splicing is a critical and tightly regulated cellular function, underlying the majority of proteomic diversity in our genomes. While disruption of this process is common in disease, the basic genetic complexity of alternative splicing in vivo remains poorly understood.  To delineate the splicing landscape in disease, we used an integrative genomics approach and combined both genome and exon level transcriptome data in two somatic tissues (cerebella and peripheral ganglia) from a transgenic mouse model of neuroblastoma, a tumor that arises from peripheral ganglia.  These data identify splicing quantitative trait loci (sQTL) that modulate differential splicing across the genome.  Among these, an sQTL at FUBP1 revealed a splicing event that modulated levels of the MYC oncoprotein in human neuroblastoma-derived cell lines and correlated with outcome in neuroblastoma.  Through this unbiased sQTL analysis, we also define de novo splicing motifs that serve as sites for recurrent mutations in cancer and lead to functional changes in exon expression, enhancing our understanding of the cancer genome.

overall_design:
Exon expression from Superior Cervical Ganglia and Cerebellum from 102 backcrossed mice (TH-MYCN, FVB/NJ and 129/SvJ) were correlated with 349 genotyping markers to identify putative sQTL
The mice were the N1 generation of a backcross between TH-MYCN (FVB/NJ background) and wild-type 129/SvJ:
TH-MYCN (FVB/NJ) + 129/SvJ -> F1 (TH-MYCN FVB/NJ,129/SVJ)
F1 (TH-MYCN FVB/NJ,129/SVJ) + 129/SvJ -> N1

first: Justin

last: Chen

first: Christopher

last: Hackett

first: Shile

last: Zhang

first: Young

middle: K

last: Song

first: Robert

middle: J

last: Bell

first: Annette

last: Molinaro

first: David

middle: A

last: Quigley

first: Allan

last: Balmain

first: Jun

first: Joseph

middle: F

last: Costello

first: W

middle: C

last: Gustafson

first: Terry

last: Van Dyke

first: Pui-Yan

last: Kwok

first: Javed

last: Khan


title: Clinical symptoms of right ventricular failure in experimental chronic pressure load are associated with progressive diastolic dysfunction

status: Public on Dec 08 2014

city: Groningen

first: vincent

last: bloks

department: Pediatrics

country: Netherlands

institute: UMCG

summary:
Right ventricular failure (RVF) due to pressure load is a major cause of death in congenital heart diseases and pulmonary hypertension. The mechanisms of RVF are yet unknown. Research is hampered by the lack of a good RVF model. Our aim was to study the pathophysiology of RVF in a rat model of chronic pressure load.
Wistar rats (n=19) were subjected to pulmonary artery banding (PAB, 1.1mm) or sham surgery (CON). All PAB rats developed RVF (reduced cardiac output, RV stroke volume, TAPSE, increased end diastolic pressure, all p<0.05 vs. CON) but clinical symptoms of RVF (inactivity, ruffled fur, dyspnea, ascites) necessitating termination ensued in a subset (5/12) of rats (RVF+) after a period of 52±5 days. Rats with RVF+ had significantly worse RV function and pericardial effusion and liver congestion compared to RVF rats without symptoms (all p<0.05), despite similar pressure load (p=NS RVF vs. RVF+).
Chronic pulmonary artery banding invariably leads to RV failure in rats, and a subset transitions to advanced clinical RVF. RVF is characterized by enhanced contractility, progressive diastolic dysfunction and derangement of energy metabolism, thus improving diastolic function and targeting RV metabolism may be the keys to treating RVF.

overall_design: Total RNA optainded ( Heart) of 7 Controls ,5 RVF+ and 4 RVF samples where used for this array study

first: M

last: Borgdorff

first: A

last: Koops

first: V

middle: W

last: Bloks

middle: G

last: Dickinson

first: P

last: Steendijk

first: H

middle: H

last: Sillje

middle: P

last: van Wiechen

first: R

last: Berger

first: B

last: Bartelds


title: Stimulating BMP4 signaling via HDAC11 inhibition suppresses malignancy in preclinical models of  human neuroblastoma

city: Goettingen

first: Gabriela

last: Salinas

state: Lower-Saxony

address: Kreuzbergring 57

department: Department of Pathology

country: Germany

institute: Universitaetsmedizin Goettingen

summary: Bone morphogenetic proteins (BMPs) trigger as cell-extrinsic signals the differentiation of neural crest progenitor cells to the sympathoadrenal cell lineage. Human neuroblastoma derives from aberrant neural crest progenitor cells. We here show that histone deacetylase 11 (HDAC11), the most recently identified family member with, as yet, largely unknown function, is recruited to the BMP4 gene promoter and represses its transcription in neuroblastoma. Both HDAC11 depletion and enzymatic inhibition revert the epigenetic silencing of BMP4, thereby blocking a critical oncogenic function of HDAC11. Activated BMP4 signaling through targeting of HDAC11 induces a transcriptional profile predictive of favorable prognosis for patients when expressed in the tumors, indicating that the HDAC11-BMP4 axis plays a critical role for neuroblastoma biology. Furthermore, pathway activation causes MYCN proto-oncogene repression on a molecular level and anti-proliferative effects in functional assays in neuroblastoma cell lines and primary sphere cultures as well as strongly inhibiting tumor formation and growth of subcutaneous neuroblastoma xenografts in mice. For high-risk neuroblastoma, with cure rates below 30% using current treatment strategies, our work suggests a novel targeted therapeutic approach that would reactivate the developmental pathway inducing normal differentiation of neural crest progenitor cells.

overall_design:
Agilent data: Common Reference Design with 48 chips including 17 different samples with 3 replicates per sample.

Illumina data: BE(2)C neuroblastoma cells were transfected with siRNAs against HDAC11 for 48h, and 96h, respectively. As controls served siRNA transfection with scrambled siRNAs. In parallel, cells were treated for 72h with the pan-HDAC inhibitor HC-toxin. As control for HC-Toxin, cells were tretaed with MeOH solvent. All experiments were performed in triplicates. RNA was prepared from cell lysates using RNeasy (Qiagen) according to manufacturer's instruction. standard procedures. RNA quality was checked with Agilent Bioanalyzer.

first: Hedwig

middle: E

last: Deubzer

first: Marco

last: Lodrini

first: Till

last: Milde

first: Marie

last: Schier

first: Ina

last: Oehme

first: Johannes

last: Schulte

first: Theresa

last: Thole

last: Fabian

first: Inga

last: Wiegand

first: Andreas

last: vonDeimling

first: Lennart

last: Opitz

first: Kathy

last: Astrahantseff

first: Alexander

last: Schramm

first: Martin

last: Michaelis

first: Benedikt

last: Brors

first: Matthias

last: Fischer

first: Angelika

last: Eggert

last: Kulozik

first: Olaf

last: Witt


title: Expression data sets for untreated and reprogrammed fibroblasts

status: Public on Dec 21 2014

city: Manchester

first: Kiran

last: Batta

address: Withington

country: United Kingdom

institute: CRUK Manchester Institute

summary: To understand global transcriptome during reprogramming fibroblasts to blood cells, we have analysed transcriptomes of untreated fibroblasts, CDH5 positives cells sorted at day 8 and C-Kit positive cells sorted at day 12.

overall_design: 6 samples, 2 biological replcated of  untreated fibrobalsts, Day 8 CDH5 positive cells, Day 12 C-Kit Positive cells


title: Genome-wide DNA methylation analysis on testicular embryonal carcinoma

status: Public on Mar 12 2015

city: CUHK, Shatin

first: Hoi-Hung

last: Cheung

address: Rm.708A, LKS Integrated Biomedical Sciences Bldg.

department: School of Biomedical Sciences

country: Hong Kong

institute: The Chinese University of Hong Kong

type: Methylation profiling by genome tiling array

summary:
Genomic DNA from 6 pure EC and 2 normal testis was fragmented and immunoprecipitated with anti-5mC monoclonal antibodies by MeDIP. After IP, DNA was purified and amplified using Whole Genome Amplification. Subsequently, DNA was biotin-labeled and hybridized to Human Tiling Array 2.0R Chips (Affymetrix) according to the manufacturer’s instruction. Raw data (CEL files) were normalized and analyzed by TAS (Affymetrix). Technical replicate of MeDIP-chip procedure was performed.
Testicular embryonic carcinoma (EC) is a major subtype of non-seminomatous germ cell tumors (NSGCTs) in males. To identify epigenetic changes during testicular tumorigenesis, we profiled the DNA methylation of 6 ECs. These samples represent different stages (stage I and stage III) and different extent of invasiveness. Non-cancerous testicular tissues were included. A total of 1167 tumor-hypermethylated differential methylated regions (DMRs) were identified across the genome. Among them, 40 genes/ncRNA were found to have hypermethylated promoters. Interestingly, we found several hypermethylated sex-linked genes, including X-linked genes STAG2, SPANXD/E, MIR1184, Y-linked genes RBMY1A1/1B/1D and FAM197Y2P. Expression of RBMY1A was confirmed by immunohistochemistry in normal germ cells, but lost in EC and seminoma. Our genome-wide analysis identified methylation changes in several previously unknown genes for testicular ECs, which might provide insight into the crosstalk between normal germ cell development and carcinogenesis.

overall_design: A total of 8 DNA samples, including 6 EC and 2 normal testicular tissues

first: Tin-Lap

last: Lee

first: Owen

last: Rennert

first: Wai-yee

last: Chan


title: Phase II study of therapy selected by tumor molecular profiling in patients with previously treated metastatic pancreatic cancer.  A study of the Stand Up to Cancer (SU2C) study consortium

city: Scottsdale

first: Michael

middle: Thomas

last: Barrett

state: AZ

address: 13400 East Shea Boulevard

department: Molecular Pharmacology and Experimental Therapeutics

institute: Mayo Clinic Arizona

summary: The study accrued 49 subjects, and 48 underwent a tumor biopsy. and MP based therapy was administered to 35 patients. Study therapy was not given in 13 subjects either due to insufficient tumor on biopsy (n=8) or due to worsening cancer related symptoms after biopsy (n=5) . The demographics of evaluable patients (n=35) are M/F (59%/41%), with and age range was 34-78 (median 63 years). Time from first diagnosis of mPC to biopsy ranged from 5.8-26.7 months (median 16.1 months). Patients had 1-6 prior regimens with a median of 2. The most common IHC targets were topoisomerase 1 or 2, thymidylate synthase, ERCC1 and SPARC. Only commercially available agents were prescribed. Common regimens/agents recommended were FOLFIRI, FOLFOX, irinotecan and doxorubicin. Response rate was 9% , overall median survival of 6 months and 1 year survival was 21%.

overall_design: Eligible mPC patients had progressive disease following  > 1 systemic therapy and a metastatic lesion amenable to percutaneous biopsy. The study required 35 evaluable patients (power of 86%) for detecting a true one year survival rate of > 20% versus the null hypothesis survival rate of < 5%. Patients underwent a percutaneous biopsy, treatment selection was based on the Target Now® IHC assay (Caris Life Sciences, Irving, TX). Samples also underwent array comparative genomic hybridization (aCGH) and microarray analysis (MA).

first: Ramesh

last: Ramanathan

first: Glen

last: Weiss

middle: T

first: Richard

last: Posner

first: Rajesh

last: Kumar

first: Gayle

last: Jameson

first: Meraj

last: Aziz

first: Antje

last: Hoering

first: Anirban

last: Maitra

first: Monica

last: Fulk

first: Mahesh

last: Seetharam

first: Manpreet

last: Chadha

first: Edward

last: Stites

first: William

last: Hlavacek

first: Manuel

last: Hidalgo

first: Daniel

last: Von Hoff


title: Identification of stage specific genes associated with lupus nephritis and response to remission induction in NZB/W and NZM2410 mice

city: Ann Arbor

first: Celine

last: Berthier

state: MI

address: 1150 W. Medical Center Dr, MSRB2

institute: University of Michigan

summary: The CEL files of this study are additional to the GSE32583 and GSE44691; they are microarrays of lupus nephritis NZBW mouse model at 30 wks old, or treated with CTX+CTLAIg+anti-CD154 (early and late after remission) or Ad-TACI-Ig+CTLA4Ig (late after remission) and NZM2410 treated with Ad-BAFF-R-Ig.

overall_design:
Expression data from lupus NZB/W mouse kidneys at 30 wks old and treated and from NZM2410 mouse kidneys treated.
RNA from whole kidneys was extracted and processed for hybridization on Affymetrix microarrays.

first: Ramalingam

last: Bethunaickan

first: Weija

last: Zhang

first: Ridvan

last: Eksi

first: Hong

last: Li

first: Yuanfang

last: Guan

first: Matthias

last: Kretzler

first: Anne

last: Davidson


title: m6A RNA modification controls cell fate transition in mouse embryonic stem cells (gene expression analysis)

status: Public on Oct 16 2014

city: Stanford

first: Kun

last: Qu

address: 269 Campus Dr. CCSR 2150

department: Dermatology

institute: Stanford University

summary: Here we determine the map of RNA methylation (m6A) in mouse embryonic stem cells, and embryoid bodies.

overall_design: Gene expression analysis: To establish the impact of METTL3 loss of function on gene expression in mESC. RNA hybridized to GeneChip Mouse Exon 1.0 ST Array

first: Pedro

last: Batista

first: Howard

middle: Y

last: Chang


title: Whole Genome Analysis of a Well-Differentiated Liposarcoma Reveals Novel SYT1 and DDR2 Rearrangements

status: Public on Jan 01 2015

first: Mitesh

last: Borad

address: 13400 E Shea Blvd

institute: Mayo Clinic in Arizona

summary: We used DNA content-based flow cytometry to distinguish and isolate nuclei from clonal populations in a single liposarcoma prior to array comparative genomic hybridization and whole genome sequencing.

overall_design: We applied DNA content based flow sorting to isolate the nuclei of clonal populations in a single liposarcoma sample prior to array comparative genomic hybridization and next generation sequencing.

first: Jan

middle: B

last: Egan

first: Michael

last: Barrett

first: Mia

last: Champion

first: Sumit

last: Middha

first: Elizabeth

last: Lenkiewicz

first: Lisa

last: Evers

first: Jessica

last: Schmidt

first: Chang-Xin

last: Shi

first: Scott

middle: V

last: Wier

first: Gregory

last: Ahmann

first: K

last: Kortuem

first: Nicole

last: Boczek

first: Rafael

last: Fonseca

first: David

last: Craig

first: John

last: Carpten

first: A

last: Stewart


title: Myeloid Dendritic Cells Induce HIV-1 Latency in Non-Proliferating CD4+ T Cells

status: Public on Nov 01 2014

city: Cleveland

first: Peter

last: Wilkinson

state: Ohio

address: 2103 Cornell Road

department: Pathology / Systems Biology & Bioinformatics

institute: Case Western Reserve University

summary: Latently infected resting CD4+ T cells are a major barrier to HIV cure. Understanding how latency is established, maintained and reversed is critical to identifying novel strategies to eliminate latently infected cells. We demonstrate here that co-culture of resting CD4+ T cells and syngeneic myeloid dendritic cells (mDC) can dramatically increase the frequency of HIV DNA integration and latent HIV infection in non-proliferating memory, but not naïve, CD4+ T cells. Gene expression in non-proliferating CD4+ T cells, enriched for latent infection, showed significant changes in the expression of genes involved in cellular activation and interferon regulated pathways, including the down-regulation of genes controlling both NF-κB and cell cycle. We conclude that mDC play a key role in the establishment of HIV latency in resting memory CD4+ T cells, which is predominantly mediated through signalling during DC-T cell contact.

overall_design: Resting (CD69-CD25-HLA-DR-) CD4+ T cells were enriched from the blood of 4 normal donors by magnetic bead depletion and labelled with the proliferation dye SNARF. SNARFhiEGFP- CD4+ T cells cultured with (+DC) or without syngeneic bulk DC (lin-HLA-DR+), in the presence (HIV T) or absence (Mock T) of HIV, were sorted 5 days following infection with NL(AD8)-nef/EGFP (MOI 5).Culture media was supplemented with 10ng/mL of IL-7.  The gene expression profile of the 4 cell populations: 1. HIV T (+DC); 2. Mock T (+DC); 3. HIV T; and 4. Mock T, was determined.

last: Vanessa

last: Filali-Mouhim

first: F

last: Procopio

first: O

last: Yegorov

first: J

last: Goulet

first: S

last: Saleh

first: E

last: Haddad

first: R

last: Sekaly

first: P

middle: U

last: Cameron

middle: R

last: Lewin

first: L

last: Pan

first: M


title: Patterns of gene expression associated with recovery and injury in heat-stressed rats

status: Public on Jan 14 2015

city: Ft. Detrick

first: Christine

last: Baer

address: 568 Doughten Drive

department: Environmental Health Program

institute: Excet, Inc. / USACEHR

summary:
Background: The in vivo gene response associated with hyperthermia and subsequent return to homeostasis or development of heat illness is poorly understood. Early activation of gene networks in the heat stress response is likely to lead to the systemic inflammation, multi-organ functional impairment, and other pathophysiological states characteristic of heat illness. Here, we perform an unbiased global characterization of the multi-organ gene response using an in vivo model of heat stress in the conscious rat.

Results: Rats were subjected to elevated temperatures until implanted thermal probes indicated a maximal core temperature of 41.8 °C (Tc,Max). Liver, lung, kidney, and heart were harvested at Tc,Max, 24 hours, and 48 hours after heat stress in groups of experimental animals and time-matched controls kept at ambient temperature. Clinical chemistries suggested abnormal function in liver, kidney, and lung at Tc,Max, and cardiac histopathology at 48 hours supported persistent cardiac damage in 3 out of 6 animals. Microarray analysis identified 78 differentially expressed genes common to all 4 organs at Tc,Max (i.e., the consensus heat stress response). Gene set enrichment analysis of gene ontology terms identified 25 biological processes in 4 general gene ontology categories: protein folding, regulation of apoptosis, response to cytokines, and transcriptional responses. Functional analysis clustering of the 78 differentially expressed genes in the consensus heat stress response also identified functional categories of protein folding and regulation of apoptosis. Self-organizing maps identified gene-specific signatures corresponding to protein folding disorders specific to only heat-stressed rats with histopathologic evidence of cardiac injury at 48 hours. Enrichment analysis of differentially expressed proteins in heat-injured hearts at 48 hours corroborated gene enrichment analysis results. Quantitative proteomics analysis by iTRAQ demonstrated that differential protein expression was not comparable to transcript expression at Tc,Max and 24 hours. However, the profile of differentially expressed proteins closely matched the transcriptomic profile in heat-injured animals at 48 hours. Pathway analysis at both the transcript and protein levels supported catastrophic deficits in energetics and cellular metabolism, chronic proteotoxic response, and activation of the unfolded protein response. Calculation of protein super-saturation scores demonstrated an increased propensity of proteins to aggregate in the hearts of heat-injured animals at 48 hours, consistent with accumulation of misfolded proteins.

Conclusions: Global transcriptomic and proteomic analysis identified networks of genes and proteins initiating an unfolded protein response, metabolic dysfunction, and mitochondrial energy crisis in animals with histopathologic evidence of persistent heat injury, providing the basis for a systems-level physiological model of heat illness and recovery.

overall_design: To induce the pathophysiological effects of heat stress, conscious rats were placed in an incubator at 37ºC and their core temperature was monitored. Animals were sacrificed when their core temperature reached 41.8ºC (Tc,Max), or they were returned to their normal housing environment and were allowed to recover for up to 24 or 48 hours prior to sacrifice. Time-matched controls were euthanized at times corresponding to Tc,Max, 24 hours, and 48 hours. For each condition n=6 for a total of 36 animals. Four tissues (liver, lung, kidney and heart) were analyzed from each animal for a total of 144 arrays; however a few arrays did not pass QC therefore only 140 are reported here: 34 liver, 35 lung, 36 kidney, or 35 heart.

first: Jonathan

middle: D

last: Stallings

first: Danielle

middle: L

last: Ippolito

first: Vineet

last: Rakesh

first: William

first: Bryan

last: Helwig

last: Jackson

first: Lisa

last: Leon

last: Lewis

first: Jaques

last: Reifman


title: Arabidopsis Col vs vim1,2,3 triple mutant

status: Public on Oct 02 2014

city: Jeju-si

first: Jeongsik

last: Kim

state: Jeju

address: 102 Jejudaehakroe

department: Faculty of Science Education

country: South Korea

institute: Jeju National University

summary: Transcriptional profiling of Arabidopsis comparing wild type with vim1,2,3 triple mutant to investigate epigenetic function of VIM family genes

overall_design: Two-condition experiment, Col vs vim1,2,3 triple. 4 independent biological samples

first: Hye Ryun

last: Woo


title: p63+/Krt5+ Distal Airway Stem Cells are Essential for Lung Regeneration (tracheal epithelium and alveoli)

status: Public on Nov 20 2014

city: Houston

first: Frank

last: McKeon

state: TX

address: 3455 Cullen Blvd

department: Biology and Biochemistry

institute: University of Houston

summary: The possibility of lung regeneration has been long discounted due to the irreversible nature of chronic lung diseases.  However, patients who sustain massive loss of lung tissue during acute infections often recover full pulmonary function.  Correspondingly, we previously demonstrated lung regeneration in mice following H1N1 influenza virus infection and implicated p63+Krt5+ distal airway stem cells, or DASCp63/Krt5, in this process.  We show here that rare, preexisting DASCp63/K5 undergo a proliferative expansion in response to influenza and lineage-trace to nascent alveoli assembled at sites of interstitial inflammation.  We also show that the ablation of DASCp63/Krt5 in vivo prevents the regeneration of lung tissue following influenza leading to pre-fibrotic lesions and deficient oxygen exchange.  Finally, we demonstrate that exogenously cloned and propagated DASCp63/Krt5 readily contribute to lung regeneration following transplantation. These data suggest that DASCp63/K5 are required for lung regeneration and may have therapeutic utility in acute and chronic lung diseases.

overall_design: Tracheal epithelium and alveoli of healthy mice were laser capture microdissected for microarray analysis.  Damaged lung interstitium (CD45+ region) of influenza infected (75pfu H1N1, 15dpi) mice were also dissected. Duplicates were included for each sample. We used the Affymetrix Mouse Exon 1.0 ST platform

first: Wei

last: Zuo

first: Ting

last: Zhang

first: Daniel

middle: Z

last: Wu

first: Shouping

last: Guan

first: Audrey

middle: A

last: Liew

first: Yusuke

last: Yamamoto

first: Tiffany

middle: S

last: Lim

first: Matthew

last: Vicent

first: Mark

last: Lessard

first: Christopher

last: Crum

first: Wa

last: Xian


title: Effect of HDAC2 siRNA on HCC

city: Copenhagen

first: Jesper

last: Andersen

address: Ole Maaloes Vej 5

department: Biotech Research and Innovation Centre

country: Denmark

institute: Copenhagen University

summary: Determine the effect and specificity of HDAC2 siRNA compared to SAHA inhibition of HDAC2 in hepatocellular carcinoma (HCC)

overall_design:
Profile of treated cells compared to control
Transcriptomic profiling

first: Snorri

last: Thorgeirsson

first: Valentina

middle: M

last: Factor


title: p63+/Krt5+ Distal Airway Stem Cells are Essential for Lung Regeneration

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

overall_design: Refer to individual Series


title: Cross-platform toxicogenomics for the prediction of nongenotoxic hepatocarcinogenesis in rat (mRNA)

status: Public on Aug 18 2014

city: Basel

first: Jonathan

last: Moggs

address: Fabrikstrasse 2

country: Switzerland

institute: Novartis

summary: In this study we performed microarray-based molecular profiling of liver samples from Wistar rats exposed to genotoxic carcinogens (GC), nongenotoxic carcinogens (NGC) or non-hepatocarcinogens (NC) for up to 14 days. In contrast to previous toxicogenomics studies aimed at the inference of molecular signatures for assessing the potential and mode of compound carcinogenicity, we considered multi-level omics data. Besides evaluating the predictive power of signatures observed on individual biological levels, such as mRNA, miRNA and protein expression, we also introduced novel feature representations which capture putative molecular interactions or pathway alterations by integrating expression profiles across platforms interrogating different biological levels.

overall_design: Male Wistar rats were treated by oral gavage with the eight nongenotoxic hepatocarcinogens Phenobarbital sodium (PB), Piperonylbutoxide (PBO), Dehydroepiandrosterone (DHEA), Acetamide (AA), Methapyrilene HCl (MPy), Methylcarbamate (Mcarb), Diethylstilbestrol (DES) and Ethionine (ETH), the two genotoxic carcinogens C.I Direct Black (CIDB) and dimethylnitrosamine (DMN), the two non-hepatocarcinogens Cefuroxime (CFX) and Nifedipine (Nif), and the three compounds with undefined carcinogenic class Cyproterone acetate (CPA), Thioacetamid (TAA) and Wy-14643 (Wy). Depending on the administered compound, livers were taken after 3, 7, or 14 days for histopathological evaluation. From the five animals per treatment group three animals were selected based on the histopathological findings and subjected to molecular profiling using Affymetrix RG-230A arrays (mRNA expression), Agilent G4473A arrays (miRNA expression) and Zeptosens ZeptoMARK reverse arrays (protein expression).

first: Michael

last: Römer

first: Heidrun

last: Ellinger-Ziegelbauer

first: Johannes

last: Eichner


title: Evaluation of Human Embryonic Stem Cells and their 1 Differentiated Fibroblastic Progenies as Cellular Models for In Vitro Genotoxicity Screening

status: Public on Jul 30 2014

city: Singapore

first: Manikandan

last: Jayapal

address: 2 Medical Drive

country: Singapore

institute: National University of Singapore

summary: This study evaluated human embryonic stem cells (hESC) and their differentiated fibroblastic progenies as cellular models for genotoxicity screening. The DNA damage response of hESCs and their differentiated fibroblastic progenies were compared to a fibroblastic cell line (HEPM, CRL1486) and primary cultures of peripheralblood lymphocytes (PBL), upon exposure to gamma irradiation.

overall_design: Radiation exposure was carried out with Gamma ® 40 extractor with the central dose rate of 1.16 Gy/minute. Radiation dose 1 Gy was used in this study. Cells were harvested 30 minutes following radiation exposure. ESCs, H1F, HEPM and PBLs with and without 1 Gy radiation exposure were used for this purpose.

first: Jayapal

last: MANIKANDAN

first: Kumar

middle: J

last: VINOTH

first: Lakshmidevi

last: BALAKRISHNAN

first: Alexis

last: HENG

first: Kai

last: LU

first: Swaminathan

last: SETHU

first: Manoor

last: HANDE

first: Tong

last: CAO


title: Gene Expression of Kidney from HSRA-S (congenital solitary kidney) and HSRA-C (two-kidney) using  Rat Gene 1.1 ST Array [RaGene-1_1-st]

status: Public on Oct 07 2014

city: Jackson

last: Garrett

state: MS

address: 2500 North State Street

department: Pharmacology

institute: University of Mississippi Medical Center

summary:
We recently developed a new model of renal agenesis [i.e., the heterogeneous stock derived model of unilateral renal agenesis, (HSRA)]. The HSRA model consistently exhibits unilateral renal agenesis ranging from 50-75% in each generation and is characterized by low nephron number, early kidney hypertrophy, and an inherent susceptibility to develop significant kidney injury and decline in renal function with age.
Whole transcriptome analysis was evaluated at month 1 to identify early changes in genes/networks that may be involved in increased susceptibility of HSRA-S to develop kidney injury in the long-term.

overall_design: An n=4 per group (independent samples) were evaluated for HSRA-S (congenital solitary kidney) and HSRA-C (two-kidney). HSRA-C (two-kidney) samples were set as the control.


title: Checkpoints Couple Transcription Network Oscillator Dynamics to Cell-Cycle Progression

status: Public on Jul 27 2014

city: Durham

first: Steven

last: Haase

department: Biology

institute: Duke University

summary: Yeast cell cycle transcript dynamics in three S. cerevisiae strains grown at 30 degrees Celsius: cdc20 GALL-CDC20 (persistent mitotic CDK activity; CDK on), cdc8-ts (DNA replication checkpoint), GAL-cse4-353 (spindle assembly checkpoint), cdc8-ts cdc20 (DNA replication checkpoint, CDK on), and cdc8-ts cdc20, rad53-1 (DNA replication checkpoint without Rad53 activity, CDK on) in a BF264-15DU background. We compared transcript levels of genes previously shown to be periodically expressed in wild-type cells and in cells lacking all mitotic cyclins (clb1,2,3,4,5,6; CDK off).

platform_organism:
Schizosaccharomyces pombe
Saccharomyces cerevisiae

overall_design: Two replicate time courses for each of the strains studied are included

first: Sara

last: Bristow

first: Adam

last: Leman

first: Laura

last: Simmons Kovacs

first: Anastasia

last: Deckard

first: John

last: Harer


title: Gene expression of hormone-treated U2OS cells expressing GR alleles

status: Public on Jul 15 2014

city: San Francisco

first: Benjamin

last: Schiller

institute: University of California, San Francisco

summary:
Glucocorticoid receptor (GR) is a hormone-activated, DNA-binding transcriptional regulatory factor, which regulates diverse aspects of physiology. GR recognizes specifically imperfect palindromic six base pair “half sites
separated by thoursee base pair “spacers”, binding as an inverted dimer. In vivo, different GR target genes depend on different functional surfaces  of GR for proper regulation, but rules dictating the relationship between
sequence and utilization of distinct GR functional surfaces remain unknown.In this study, we measured changes in gene expression and genomic occupancy upon glucocorticoid treatment of isogenic cultured human
cell lines expressing alleles of GR bearing differences in particular functional surfaces.

overall_design:
Total RNA was isoalted from U2OS cells expressing GRalpha, GRgamma, A477T, 30iiB, or E773R after treatment with 100 nM dexamethasone for 2, 4, or 24 hours, or ethanol for 4 hours (0 hours).
There are four biological replicates of each condition.

first: Rajas

last: Chondankar

first: Lisa

middle: C

last: Watson

first: Michael

last: Stallcup

first: Keith

last: Yamamoto


title: RNA profiling from ovarian FFPE specimens (Nanostring)

status: Public on Jul 01 2014

city: Boston

first: Svitlana

last: Tyekucheva

address: 450 Brookline Ave

institute: Dana-Farber Cancer Institute

summary: To study feasibility of gene expression profiling from FFPE tissues using NanoString nCounter platform, we designed a pilot study utilizing samples from ovarian cancer cohort. We selected samples from large-scale epidemiologic studies and clinical trials representative of a wide variety of fixation times, block ages and block storage conditions.

overall_design: five serous carcinoma and six clear cell carcinoma samples with technical replicates


title: MicroRNA expression array for 1833 cells expressing RKIP vs. control

city: Chicago

first: Miao

last: Sun

institute: University of Chicago

summary: RKIP has been implicated in suppression of breast tumor metastasis. Identification of microRNAs regulated by RKIP helps us to understand how RKIP suppresses tumor metastasis via its downstream target mircoRNAs and genes.

overall_design: Total RNA was extracted from 1833 cells expressing RKIP or control, respectively. Exiqon miRCURY LNA array v.11.0. was performed to identify the microRNAs regulated by RKIP.

first: Marsha

last: Rosner


title: Distribution of segmental duplications in the context of higher order chromatin organisation of human chromosome 7

city: Berlin

first: Reinhard

last: Ullmann

department: Human Molecular Genetics

institute: MPIMG

type: Genome binding/occupancy profiling by genome tiling array

summary:
Background
Segmental duplications (SDs) are not evenly distributed along chromosomes. The reasons for this biased susceptibility to SD insertion are poorly understood. Accumulation of SDs is associated with increased genomic instability, which can lead to structural variants and genomic disorders such as the Williams-Beuren syndrome. Despite these adverse effects, SDs have become fixed in the human genome. Focusing on chromosome 7, which is particularly rich in interstitial SDs, we have investigated the distribution of SDs in the context of evolution and the three dimensional organisation of the chromosome in order to gain insights into the mutual relationship of SDs and chromatin topology.

Results
Intrachromosomal SDs preferentially accumulate in those segments of chromosome 7 that are homologous to marmoset chromosome 2. Although this formerly compact segment has been re-distributed to three different sites during primate evolution, we can show by means of public data on long distance chromatin interactions that these three intervals, and consequently the paralogous SDs mapping to them, have retained their spatial proximity in the nucleus. Focusing on SD clusters implicated in the aetiology of the Williams-Beuren syndrome locus we demonstrate by cross-species comparison that these SDs have inserted at the borders of a topological domain and that they flank regions with distinct DNA conformation.

Conclusions
Our study suggests a link of nuclear architecture and the propagation of SDs across chromosome 7, either by promoting regional SD insertion or by contributing to the establishment of higher order chromatin organisation themselves. The latter could compensate for the high risk of structural rearrangements and thus may have contributed to their evolutionary fixation in the human genome.

overall_design:
2 cell lines-5 samples: 2x DNA fragmentation during apoptosis; 3x ChIP (2x H4K8ac, 1x H3)
IMR90: 1x DNA fragmentation during apoptosis; 1x H4K8ac ChIP. Both hybridized on a custom designed 4x 180k oligonucleotide microarray


title: RNA profiling from prostate FFPE specimens  (Nanostring)

summary: To study feasibility of gene expression profiling from FFPE tissues using NanoString nCounter platform, we designed a pilot study utilizing samples from prostate cancer cohort. We selected samples from large-scale epidemiologic studies and clinical trials representative of a wide variety of fixation times, block ages and block storage conditions.

overall_design: five paired tumor and adjacent normal prostate tissue speciemens with technical replicates


title: Internal validation cohort of breast cancers for development of ClinicoMolecular Triad Classification

status: Public on Jun 19 2014

city: Toronto

first: Dong-Yu

last: Wang

address: 610 University Ave

institute: UHN-PMH-OCI

summary: In our early study (PMID: 21939527), we have created a ClinicoMolecular Triad Classification (CMTC) to improve prediction and prognostication of breast cancer by using a training cohort contained 161 breast cancer patients (2003 to 2008). Here, a supplemental internal validation cohort contained 340 breast cancer patients was collected (2008 to 2010) for development of the CMTC.

overall_design:
Total 340 fine-needle aspirates (FNA) specimens from breast tumors without replicate were collected and prepared for microarray examination. Finally, 284 invasive breast cancers were used in this study.

The training dataset of 161 breast tumors can be found at GEO Accession: GSE16987.

first: Dong

first: Wey

last: Leong


title: A rat toxicogenomics study with Calcium Sensitizer EMD 82571 reveals a pleiotropic cause and adverse outcome pathway of teratogenicity

status: Public on Jun 07 2014

city: Hannover

first: Juergen

last: Borlak

state: Lower Saxony

address: Feodor-Lynen-Str. 35

department: Centre for Pharmacology and Toxicology

institute: Hannover Medical School

summary: The aim of reprotoxicity testing is to reveal adverse effects of chemicals and drugs on reproduction and on pre and postnatal fetal development. There is very limited data available on gene expression profiling for elucidation of the teratogenic effects of nongenotoxic teratogens. Therefore, research was undertaken to obtain knowledge on the molecular effects of MSC1096199 (previously known as EMD 82571), a calcium sensitizer that was abandoned in the preclinical development phase due to its teratogenic effects in some foetuses. Pregnant wistar rats were dose daily with either MSC1096199 (50 or 150 mg/kg) or Retinoic acid (12 mg/kg) on gestational days 6-17. Microarray experiment were performed using four different tissues (maternal liver, embryo liver (GD20), embryo bone (GD20), and whole embryo (GD12)) under four different conditions (vehicle, low dose and high dose of MSC1096199 and Retinoic acid) to determine the drug regulated genes. In the high dose treatment group, approximately 58% of the fetuses showed malformations i.e. exencephaly and agnathia, and toxicogenomics evidenced that the genes critically involved in osteogenesis, odontogenesis and extra cellular matrix components to be significantly regulated by MSC1096199, therefore providing a molecular rational for the observed teratogenic effects.

overall_design: Pregnant wistar rats were treated daily with the dose of either MSC1096199 (50 or 150 mg/kg) or Retinoic acid (12 mg/kg) on gestational days 6-17. Microarray experiment were performed using four different tissues (maternal liver, embryo liver, embryo bone, and whole embryo) under four different conditions (vehicle, low dose and high dose of MSC1096199 and Retinoic acid) to determine the drug regulated genes.

first: Jurgen

first: Prafull

middle: K

last: Singh

first: Arun

last: Kumar


title: Regulation of Pkm2 by miR-122.

status: Public on Jun 08 2014

city: Oakland

first: Christine

last: Jung

address: PO Box 22688

institute: University of California Davis

summary: The study identified Pkm2 to be highly expressed in human embryonic stem cells and hepatocellular carcinoma cells, and targeted by a microRNA that is highly expressed in human primary hepatocytes.

overall_design: Gene expression patterns were compared from total RNA obtained from human embryonic stem cells, human primary hepatocytes, and hepG2 and hep3B.


title: Differential actions of selective frankincense essential oil versus non-selective sandalwood essential oil induced bladder cancer cell cytotoxicity: A microarray and bioinformatics approach

status: Public on Jun 10 2014

city: Richmond

first: Mikhail

last: Dozmorov

state: VA

address: 830 E Main St

department: Biostatistics

institute: Virginia Commonwealth University

summary:
Background: Frankincense (Ru Xiang) and sandalwood (Tan Xiang) are ingredients used in traditional Chinese medicine, and have been recognized as cancer preventive and therapeutic agents. Hydrodistillation of frankincense gum resins and sandalwood heartwood to prepare essential oils is a method to extract biologically active ingredients from these plant-derived products. This study was designed to differentiate frankincense (Boswellia carterii) and sandalwood (Santalum album) induced anti-proliferative and pro-apoptotic activities in cultured human bladder cancer cells. Methods: Frankincense and sandalwood essential oils-mediated cytotoxicity was studied in established human bladder cancer J82 cells and immortalized normal human bladder urothelial UROtsa cells using a colorimetric assay. Essential oils-activated gene expression and pathway activation in human bladder cancer J82 cells were identified using high density microarray and bioinformatics techniques.
Results: Human bladder cancer cells were more sensitive to immortalized normal bladder cells with suppressed viability following frankincense essential oil exposure. In contrast, both cancerous and normal bladder cells responded to sandalwood essential with similar levels of cytotoxicity. Based on microarray and bioinformatics analyses, genes responsible for suppressing biological processes and apoptosis were induced in J82 cells by both essential oils. Although both frankincense and sandalwood essential oils activated common ontologies and canonical pathways leading to suppressed J82 cell viability and apoptosis, each essential oil had unique property on these cells. For example, heat shock proteins and histone core were ongologies regulated by frankincense essential oil, whereas transcription regulation and G-protein couple receptor were ontologies unique to sandalwood essential oil treatment. In addition, NRF-2 mediated oxidative stress was implicated as the primary cause of frankincense essential oil-induced J82 cell death; in contrast, DNA damage and cell cycle arrest might be attributed to sandalwood essential oil-mediated cytotoxicity. Conclusion: Based on cell biology and comprehensive gene expression analysis, our results provide a preliminary, yet focused characterization of genetic responses to frankincense and sandalwood essential oils with respect to their proposed anti-neoplastic properties. Modern biomedical technologies are powerful tools to study biological responses following treatments with traditional Chinese medicine, which always consist of complex chemical constituents.

overall_design: To differentiate mechanisms of frankincense and sandalwood essential oils induced cytotoxicty in bladder cancer J82 cells, time-dependent transcriptoms expression was performed in cultured cells following essential oils treatments

middle: G

first: Qing

last: Yang

first: Weijuan

last: Wu

first: Jonathan

last: Wren

first: Mahmoud

last: Suhail

first: Cole

last: Woolley

first: D

last: Youn

first: Kar-Ming

last: Fung

first: Hsueh-Kung

last: Lin


title: Human BRAF-V600E melanoma cell lines drug sensitive vs drug resistant

status: Public on Apr 21 2014

city: Philadelphia

first: Katherine

last: Nathanson

state: PA

address: 421 Curie Blvd

institute: Perelman School of Medicine at the University of Pennsylvania

summary: aCGH of human melanoma cell lines comparing parental (drug sensitve) vs isogenic drug resistant-derived subline

overall_design: Two condition experiment: two BRAF-V600E mutant cell lines (drug sensitive - parental baseline) vs two derived sublines after chronic exposure to the MEK inhibitor trametinib (drug resistant) are compared

first: Jessie

last: Villanueva

first: Bradley

last: Wubbenhorst


title: Diabetic lung

status: Public on Apr 22 2014

city: Cleveland

first: Erik

last: van Lunteren

state: OH

address: 10701 East Boulevard

department: Pulmonary 111J(W)

institute: Cleveland VA Medical Center

summary: Effect of type 1 diabetes (induced by streptozotocin 60 mg/kg) on lung gene expression.  Wistar rats, male.  At age 8 weeks control rats got IP buffer, diabetic rats got streptozotocin.  At age 12 weeks animals were anesthetized and lungs removed.  RNA was extracted with Trizol, and gene expression array analysis was performed using Affymetrix RAE 230A microarrays according to the directions from the manufacturer.  Arrays were scanned using a Hewlett Packard Gene Array scanner, and analyzed with Affymetrix MAS 5.0 software.  Expression levels reported are the output from the MAS software.

overall_design:
Control rats (n=5) vs diabetic rats (n=7)

Each sample is from a different animal (thus these are biological replicates).  Samples were NOT pooled.  Thus each sample corresponds to one animal.


title: Loss of nuclear TDP-43 in ALS causes altered expression of splicing machinery and widespread dysregulation of RNA splicing in motor neurons [NSC34]

status: Public on Jun 01 2014

city: Sheffield

first: Paul

middle: Roy

last: Heath

state: S. Yorks

address: SITraN, 385a Glossop Road

department: Academic Neurology Unit

institute: University of Sheffield

summary:
Aims: Loss of nuclear TDP-43 characterises sporadic and most familial forms of amyotrophic lateral sclerosis (ALS). TDP-43 (encoded by TARDBP) has multiple roles in RNA processing. We aimed to determine whether 1) RNA splicing dysregulation is present in lower motor neurons in ALS and in a motor neuron-like cell model, and 2) TARDBP mutations (mtTARDBP) are associated with aberrant RNA splicing using patient-derived fibroblasts.
Methods: Affymetrix exon arrays were used to study mRNA expression and splicing in lower motor neurons obtained by laser capture microdissection of autopsy tissue from individuals with sporadic ALS and TDP-43 proteinopathy. Findings were confirmed by qRT-PCR and in NSC34 motor neuronal cells following shRNA-mediated TDP-43 depletion. Exon arrays and immunohistochemistry were used to study mRNA splicing and TDP-43 expression in fibroblasts from patients with mtTARDBP-associated, sporadic and mutant SOD1-associated ALS.
Results: We found altered expression of spliceosome components in motor neurons and widespread aberrations of mRNA splicing that specifically affected genes involved in ribonucleotide binding. This was confirmed in TDP-43 depleted NSC34 cells. Fibroblasts with mtTARDBP showed loss of nuclear TDP-43 protein and demonstrated similar changes in splicing and gene expression, that were not present in fibroblasts from patients with sporadic or SOD1-related ALS.
Conclusion: Loss of nuclear TDP-43 is associated with RNA processing abnormalities in ALS motor neurons, patient-derived cells with mtTARDBP, and following artificial TDP-43 depletion, suggesting that splicing dysregulation directly contributes to disease pathogenesis. Key functional pathways affected include those central to RNA metabolism.

overall_design: RNA was extracted from NSC34 motor neuronal cells depleted of TDP-43 by shRNA (n=4), treated with control shGFP (n=4), and treated with control shLuciferase (n=3).

first: J

last: Highley

first: Janine

last: Kirby

first: Joeri

last: Jansweijer

first: Philip

last: Webb

first: Channa

last: Hewamadduma

first: Adrian

last: Higginbottom

first: Rohini

last: Raman

first: Laura

last: Ferraiuolo

first: Scott

middle: P

last: Allen

last: Cooper-Knock

first: Christopher

last: McDermott

first: Stephen

last: Wharton

first: Pamela

last: Shaw

last: Ince


title: STAG2 is a clinically relevant tumor suppressor in pancreatic ductal adenocarcinoma

status: Public on Jan 24 2014

city: Scottsdale

first: Michael

middle: Thomas

last: Barrett

address: 13400 East Shea Boulevard

institute: Mayo Clinic Arizona

summary: STAG2 is targeted by somatic aberrations in a subset (4%) of human PDAs. Transposon mediated disruption of STAG2 in a KRASG12D genetically engineered mouse model promotes the development of PDA and its progression to metastatic disease. There was a statistically significant loss of STAG2 protein expression in human tumor tissue (Wilcoxon-Rank test) with complete absence of STAG2 staining observed in 15 (4.3%) patients. In univariate Kaplan Meier analysis nearly complete STAG2 positive staining (> 95% of nuclei positive) was associated with a median survival benefit of 6.41 months (p = 0.031). The survival benefit of adjuvant chemotherapy was only seen in patients with a STAG2 staining of less than 95% (median survival benefit 7.65 months; p = 0.028). Multivariate Cox Regression analysis showed that STAG2 is an independent prognostic factor for survival in pancreatic cancer patients. Finally we show that RNAi mediated knockdown of STAG2 selectively sensitizes human PDA cell lines to platinum-based therapy.

overall_design: We used DNA content flow sorting to identify and purify tumor nuclei of PDA samples from 50 patients. The genome of each sorted sample was profiled by oligonucleotide comparative genomic hybridization (aCGH) and targeted resequencing of STAG2. Transposon insertions within STAG2 in a KRASG12D driven genetically engineered mouse (GEM) model of PDA were screened by RT-PCR. We then used a tissue microarray (TMA) to survey STAG2 protein expression levels in 344 human PDA tumor samples and adjacent tissues. Univariate Kaplan Meier analysis and multivariate Cox Regression analysis was used to assess the association of STAG2 expression relative to overall survival and responses to adjuvant therapy. Finally RNAi based assays with PDA cell lines were used to assess the potential therapeutic consequence of STAG2 expression in responses to 18 therapeutic agents.

first: Lisa

last: Evers

first: Pedro

last: Perez-Mancera

first: Elizabeth

last: Lenkiewicz

first: Nanyun

last: Tang

first: Daniela

last: Aust

first: Thomas

last: Knösel

first: Petra

last: Rümmele

first: Tobias

last: Zellweger

first: Tara

last: Holley

first: Michelle

last: Kassner

first: Meraj

last: Aziz

first: Ramesh

last: Ramanathan

first: Daniel

last: Von Hoff

first: Holly

last: Yin

first: Christian

last: Pilarsky

middle: T


title: Global transcriptional assessment of consecutive samples from patients with dengue infection with association to dengue virus IgG serostatus

status: Public on Apr 01 2014

first: Ahmad Nazri

last: Mohamed Naim

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

department: Infectious disease

institute: Genome institute of Singapore

summary: Whole blood from patients with acute dengue infection (as determined with PCR) were assessed for global transcriptional changes during different stages of the disease with reference to dengue virus IgG status at study inclusion

overall_design: Whole blood collected in PAX-gene tubes and extracted for total RNA

first: Ahmad

middle: N

last: Naim

last: Tolfvenstam

first: Anna

last: Lindblom

first: Martin

last: Hibberd


title: Gene expression anaylsis of tumor stimulated human NK cells

status: Public on Mar 18 2014

first: Vivek

last: Tanavde

state: Singapore

address: 30 Biopolis Street, #07-01, Matrix

department: Genome and Gene Expression Data Analysis Division

institute: Bioinformatics Institute, A*STAR, Singapore

summary: Genome wide expression profiling of human NK cells stimulated with K562 erythroleukemic tumor cells after four hours of NK-tumor co-culture. Responding NK cells were compared to non-responding NK cells, delineated by display of CD107 on the NK cell surface following cytotoxic granule release. We hypothesized that tumor responses would initiate rapid changes in gene expression in the NK cell that would identify new features of the anti-tumor response of NK cells. Results identify NK cell activation responses and induction of TNF superfamily molecules with immunoregulatory activity.

overall_design: Human peripheral blood NK cells were co-cultured with tumor target cell line K562 for 4 hours with GolgiStop (brefeldin) then stained for granule exocytosis marker CD107a / CD107b, and NK cell markers then FACS sorted for responding NK cells (CD107+) and non-responding NK cells (CD107-). Pooled donor sample comprised NK cells from 3 individuals.

first: Candida

last: Vaz

first: Tim

last: Holmes

first: Graham

last: Cook


title: Identification and control of host innate disease causing responses to dengue infection

summary: Our hypothesis is that dengue induces different innate immune responses in patients with mild respective severe dengue. We further hypothesize that severe dengue infection is a consequence of an over reactive inflammatory response which could be inhibited in an early stage by immune suppressants. We hypothesize that the drugs used in this study induce a down regulated inflammatory response; VP-16 by triggering apoptosis and Rosiglitazone by inhibiting NFkB related cytokine production

overall_design: In-vitro dengue infected U937, transcriptional assessment

first: Thomas


title: Genome-Wide Expression Profiling Identifies Type 1 Interferon Response Pathways in Active Tuberculosis

status: Public on Mar 25 2014

summary: Whole-genome expression profiling on a cohort of TB patients. Tuberculosis patients above 15 years of age were recruited from an outpatient tuberculosis clinic in central Jakarta (Indonesia). Randomly selected control subjects with the same sex and age (+/-10%) were recruited from neighboring households, with first degree relatives excluded.

overall_design: Total RNA obtained from human whole blood of TB patients longitudinally sampled along 3 time-points: during active infection, during treatment, and after completion of curative treatment

first: Tom

middle: H

last: Ottenhoff

first: Ranjeeta

last: Dass

first: Ninghan

last: Yang

first: Mingzi

last: Zhang

first: Hazel

middle: E

last: Wong

first: Edhyana

last: Sahiratmadja

first: Chiea

last: Khor

first: Bachti

last: Alisjahbana

first: Reinout

last: van Crevel

first: Sangkot

last: Marzuki

first: Mark

last: Seielstad

first: Esther

last: van de Vosse


title: Loss of nuclear TDP-43 in ALS causes altered expression of splicing machinery and widespread dysregulation of RNA splicing in motor neurons

first: Paul

last: Heath

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

sample_organism:
Homo sapiens
Mus musculus

platform_organism:
Homo sapiens
Mus musculus

overall_design: Refer to individual Series


title: ROR1 Can Interact With TCL1 And Enhance Leukemogenesis in Eµ-TCL1 Transgenic Mice

status: Public on Jan 02 2014

city: La Jolla

first: Emanuela

middle: Maria

last: Ghia

address: 9310 Athena Circle

department: Center For Novel Therapeutics

institute: University of California San Diego

summary:
Transcriptome analysis of RNA samples from leukemia cells of ROR1xTCL1 and TCL1 transgenic mice
Animals engrafted with ROR1xTCL1 leukemia-cells developed more aggressive disease than mice engrafted with TCL1 leukemia cells.  Transcriptome analysis of RNA samples from leukemia ROR1xTCL1 transgenic mice revealed shared common gene expression signatures that were distinct from those of TCL1 leukemia-cells.

overall_design: We performed microarray transcriptome analyses on isolated leukemia cells that developed in ROR1xTCL1 Tg mice (n=4) or TCL1 Tg mice (n=4) using the Affymetrix Mouse Exon 1.0 ST platform. Array data was processed by Affymetrix Exon Array Computational Tool. No techinical replicates were performed.

first: George

middle: F

last: Widhopf II

first: Bing

last: Cui

first: Liguan

last: Chen

first: Karen

last: Messer

first: Zhouxin

last: Shen

first: Steven

last: Briggs

first: Carlo

last: Croce

last: Kipps


title: Tissue culture model of hypoxia

status: Public on Mar 01 2014

city: Tartu

first: Sten

last: Ilmjärv

state: Tartumaa

address: Ravila 19

department: Institute of Biomedicine and Translational Medicine

country: Estonia

institute: University of Tartu

summary: Validation of an in vitro model of hypoxia using a primary cell culture of mouse embryonic fibroblasts (MEF) exposed to 1% oxygen at 37 degrees celsius. Control cells were exposed to atmospheric oxygen.

overall_design: Hypoxic and normoxic MEF (in 100 mm dishes, four replicates per group) were submitted to gene expression analysis using Affymetrix Exon microarrays. Differential gene expression analysis was performed with R package DEMI (http://biit.cs.ut.ee/demi/).

first: Hendrik

last: Luuk

first: Christian

last: Hundhal

first: Riin

last: Reimets

first: Margus

last: Niitsoo

first: Raivo

last: Kolde

first: Jaak

last: Vilo

first: Eero

last: Vasar


title: Peripheral blood gene expression in human experiencing primary EBV infection (Ref8)

status: Public on Dec 31 2013

city: Minneapolis

first: Samantha

last: Dunmire

state: MN

address: 2101 6th St SE

institute: University of Minnesota

summary: Epstein Barr virus causes linfectious mononucleosis and establishes lifelong infection associated with cancer and autoimmune disease.  To better understand immunity to EBV, we performed a prospective study of natural infection in healthy humans.  These anlyses were undertaken in order to determine what gene expression changes occur as the result of primary Epstein Barr virus infection.  Samples were taken both before and following acquisition of the virus for direct comparison of samples for single subjects.  These data provide an important first description of the response to natural herepesvirus infection in humans.

overall_design: PBMC were taken before acquisition of EBV, during acute infection, and during latency

first: Kristin

last: Hogquist


title: Expression data from Mst knockout embryoid bodies and wild type embryoid bodies

city: Hong Kong

first: Ping

last: Yuan

address: Prince Wales Hospital

department: Chemical Pathology

institute: The Chinese University of Hong Kong

summary:
Mst1/Mst2 are central components of Hippo pathway. We examined the role of Mst1/Mst2 in ES cell differentiation.
In this data set, we include expression data from day 4 and day 8 Mst1/Mst2 knockout ES cell formed embryoid bodies and wild type embryoid body controls.

overall_design: total 4 samples.

first: Peng

last: Li


title: Global transcriptional changes induced by rhinovirus infection in-vitro

city: Singapore

first: Ahmad Nazri

last: Mohamed Naim

summary: Cell lines B2B and 16HBE were infected in-vitro with rhinovirus 16 and comparisons were made to mock-infected cultures and cultures exposed to UV-irradiated rhinovirus. Total RNA were extracted and assessed by whole genome expression arrays.

overall_design: Rhinovirus in-vitro infected cell lines harvested at different time points (T hours) in biological triplicates. Total RNA extracted directly upon harvest.

first: Ahmad

last: Naim

first: Michelle

last: Wong

first: Thomas

last: Tolfvenstam

first: Martin

middle: L

last: Hibberd


title: Gene expression data from rat cochlear lateral wall after 3NP damage

status: Public on Nov 20 2013

city: Tokyo

first: Masato

last: Fujioka

address: 35 Shinanomachi Shinjuku

department: Otorhinolaryngology

institute: Keio University School of Med

summary:
A rat model of acute mitochondrial dysfunction in the cochlea is created by applying an irreversible mitochondrial complex II enzyme inhibitor, 3-NP, directly to the round window membrane. Treatment with 300 mM 3-NP results in temporary hearing loss (temporary threshold shift (TTS) model), whereas treatment with 500 mM 3-NP results in profound and permanent hearing loss (permanent threshold shift (PTS) model. Either treatment results with a primary histological change in the lateral wall spiral ligament. Because local ATP deprivation in the inner ear results from inhibition of inner ear mitochondrial function, this model replicates the etiology of inner ear energy failure caused by ATP deprivation due to inner ear ischemia.
We used microarrays to detail the global programme of gene expression in the damaged cochlear lateral wall by 3NP and identified distinct classes of up-regulated/ down-regulated genes during the process.

overall_design: One and three day after administrated either 300 mM of 3-NP (TTS-1d and TTS-3d, respectably) or saline (Ctrl-1d and Ctrl-3d, respectably), rat cochear lateral wall in the apical side of the basal turn was harvested for RNA extraction and hybridization on Affymetrix microarrays.

first: Matsunaga

last: Tatsuo


title: A systems biology-based approach to deciphering the etiology of steatosis employing patient-derived dermal fibroblasts and iPS cells

first: Justyna

last: Jozefczuk

address: Ihnestrasse 63

department: Vertebrate Genomics

institute: Max Planck Institute for Molecular Genetics

summary: We demonstrate how a multidisciplinary approach encompassing cellular reprogramming, transcriptomics, proteomics, metabolomics, modeling, network reconstruction and data management can be employed to unveil the mechanisms underlying the progression of steatosis. Proteomics revealed reduced AKT/mTOR signaling in fibroblasts derived from steatosis patients and further establishes that the insulin-resistant phenotype is present not only in insulin-metabolizing central organs, e.g. the liver, but is also manifested in skin fibroblasts. Transcriptome data enabled the generation of a regulatory network based on the transcription factor SREBF1, linked to a metabolic network of glycerolipid and fatty acid biosynthesis including the downstream transcriptional targets of SREBF1 which include LIPIN1 (LPIN) and low density lipoprotein receptor (LDLR). Glutathione metabolism was among the pathways enriched in steatosis patients in comparison to healthy controls. By using a model of the glutathione pathway we predict a significant increase in the flux through glutathione synthesis as both gamma-glutamylcysteine synthetase and glutathione synthetase have an increased flux.  The transcriptomes of dermal fibroblasts derived from two patients with steatosis (60 yr, male BMI 45.7 (H0008) and 33 yr, female, BMI 51.3 (H0007)) and control fibroblasts (19 yr, female, BMI 21, (H0002)) were analyzed.

overall_design: Total RNA obtained from dermal fibroblasts derived from two patients with steatosis (60 yr, male BMI 45.7 (H0008) and 33 yr, female, BMI 51.3 (H0007)) and control fibroblasts (19 yr, female, BMI 21, (H0002)).


title: Gene expression profile changes in HDAC6 knockdown HT1080 cells cells after TLR3 stimulation

first: Ganes

middle: C.

last: Sen

address: 9500 Euclid Avenue NE-20

institute: Cleveland Clinic

summary: TLR3 stimulation by extracellular dsRNA (e.g. polyIC) induces expression of numerous genes. The knockdown of HDAC6 prior to TLR3 stimulation leads to an ablation of expression of IRF-3-dependent genes.

overall_design: Total RNA extracted from HT1080 cells expressing control-shRNA or HDAC6-shRNA, after 6 h of treatment with dsRNA (polyIC), compared to untreated controls


title: Transcriptomic analysis of targets regulated by miR-146a in primary endothelial cells

status: Public on Dec 21 2013

city: Liege

first: Ingrid

last: Struman

address: Avenue de l'Hôpital, 1

department: BMGG

country: Belgium

institute: GIGA-R

summary: Human vein umbilical endothelial cells (HUVEC) were transfected with pre-miR control and pre-miR 146 (Ambion) in order to identify targets (direct and indirect) downregulated by miR-146a in endothelial cells. 164 transcripts were downregulated with a fold change ≥ 1.2.

overall_design: Total RNA was obtained from cells transfected in HUVEC with pre-miR control and pre-miR 146a. Three independent transfections were performed for each condition. 2 replicates for control re-control and 3 for pre-miR 146a were analyzed.

first: Julie

last: Halkein

first: Sébastien

last: Tabruyn


title: The relationship between DNA methylation, genetic and expression inter-individual variation in untransformed human fibroblasts [expression profiling]

status: Public on Dec 13 2013

city: Montreal

first: Stephan

last: Busche

state: Quebec

address: 740 Dr. Penfield Avenue

department: Human Genetics

institute: McGill University

summary:
Background:  DNA methylation has long been known to play an essential role in the epigenetic regulation of gene expression and other cellular functions, and has been in some cases linked to genetic variation. While its presence near the transcription start site of a gene has been associated with reduced expression, the variation in methylation levels across individuals, its environmental or genetic causes, and its association with gene expression remain poorly understood.
Results:  We report the joint analysis of sequence variants, gene expression and DNA methylation in primary fibroblast samples derived from a set of 62 unrelated individuals. Approximately 2% of the most variable CpG sites are mappable in cis to sequence variation, usually within 5kb. Via eQTL analysis with microarray data combined with mapping of allelic expression regions, we obtained a set of 2770 regions mappable in cis to sequence variation. In 9.5% of these expressed regions, an associated SNP was also a methylation QTL. Methylation and gene expression are often correlated without direct discernible involvement of sequence variation, but not always in the expected direction (negative for promoter CpGs, positive for gene body CpGs). Population-level correlation between methylation and expression is strongest in a subset of developmentally significant genes, including all four HOX clusters. The presence and sign of this correlation are best predicted using specific histone marks or DNase I hypersensitivity rather than position of the CpG site with respect to the gene, showing that other epigenetic markers are necessary to interpret downstream effects of individual methylation variants.
Conclusion:  Our results indicate a wide variety of relationships between gene expression, DNA methylation and sequence variation in untransformed adult human fibroblasts, with considerable involvement of chromatin features. We note particularly high levels of variation and correlation in DNA methylation and gene expression at key developmental loci, with little discernible involvement of sequence variation.

overall_design: Ref-8 Gene Expression Data for human primary fibroblast lines

first: James

last: Wagner

first: Tony

last: Kwan

first: Bing

last: Ge

first: Tomi

last: Pastinen

first: Mathieu

last: Blanchette


title: Transcription profile of colon biopsies from normal (NOR) donors, patients, underwent resection for CRC (M-CRC) and patients carriers of mutations predisposed to HNPCC (HNPC)

status: Public on Nov 30 2013

city: Torino

first: Raffaele

middle: A

last: Calogero

state: To

address: Via Nizza 52

department: Molecular Biotechnology Center

country: Italy

institute: University of Torino

summary: The challenge of preventing colorectal cancer (CRC) is the early identification of individuals whose apparently normal colorectal mucosa will develop cancer, because of inherited trait or environmental exposure. We sought to use genome-wide expression profiling of endoscopic biopsies to detect a signature of propensity for cancer. We performed oligonucleotide microarray analysis of normal appearing mucosa of the following cases: healthy individuals, disease-free carriers predisposed to HNPCC (hereditary non-polyposis CRC), disease-free patients who underwent curative large bowel resection for CRC 1 to 15 years earlier and patients with CRC.

overall_design: This profiling is based on the analysis of 4 donors who underwent curative large bowel resection for CRC from 1 to 19 years before (M-CRC samples), 4 disease-free carriers of mutations in the mismatch repair system genes, who are predisposed to develop HNPCC (HNPCC samples) and 4 endoscopy-negative, asymptomatic individuals (NOR samples)

first: Martina

last: Olivero

first: Giovanni

last: Galatola

first: Cristiana

last: Laudi

first: Stefania

last: Crispi

first: Daniela

last: Cantarella

first: Mario

last: Morino

first: MariaFlavia

last: Direnzo


title: Integrative DNA methylation and gene expression analysis in high-grade soft tissue sarcomas [methylation]

status: Public on Nov 16 2013

city: Heidelberg

first: Marcus

last: Renner

address: Im Neuenheimer Feld 224

department: General Pathology

institute: Institute of Pathology

summary: We used the Infinium HumanMethylation27 platform to profile DNA methylation in 80 primary, untreated high-grade soft tissue sarcomas, representing eight relevant subtypes, two non-neoplastic fat samples and 14 representative sarcoma cell lines.

overall_design: Marcus, Renner

first: Thomas

last: Wolf

first: Gunhild

last: Mechtersheimer


title: Enhancers of Polycomb 1 & 2 in normal and leukaemic haematopoiesis

status: Public on Oct 30 2013

city: Manchester

first: Tim

last: Somervaille

state: Lancashire

address: Wilmslow Road

institute: Cancer Research UK Manchester Institute

summary: A knockdown screen of chromatin regulatory genes in human THP1 MLL-AF9 AML cells identified EPC1 and EPC2 as required for cell survival. Normal myeloid progenitor cells did not require EPC1 or EPC2 for their function. To determine the transcriptional consequences of EPC knockdown, normal murine granulocyte-macrophage progenitor (GMP) cells, or murine MLL-AF9 AML GMP-like cells, were FACS purified from mice and infected with lentiviral vectors targeting EPC1 or EPC2 for knockdown, or a non-tageting control. 42 hours later knockdown or control cells were FACS purified and exon array analysis was performed on the sorted populations.

overall_design: For normal GMP cells, three biological replicates (three separate animals) each of control cells, EPC1 knockdown cells and EPC2 knockdown cells; for MLL-AF9 AML GMP-like cells cells, three biological replicates (three separate leukaemias) each of control cells, EPC1 knockdown cells and EPC2 knockdown cells.


title: Genome wide expression profiling of anterior tongue cancer with no history of tobacco and alcohol use

status: Public on Nov 05 2013

city: Trivandrum

first: Ramkumar

last: Hariharan

state: Kerala

address: Poojapura, Thycaud PO

department: Cancer Research Program

country: India

institute: Rajiv Gandhi Center for Biotechnology

summary: We employed high-throughput gene expression profiling to understand gene expression differences between habits-associated tongue cancers and non-habits tongue cancers. Expression data from 22 tumors were used to identify a set of 18 differentially expressed genes that can, with high precision, distinguish the two etiologically diverse oral tumors. Results from the study provide insights into molecular carcinogenesis of tongue cancers without a history of tobacco and alcohol use.

overall_design: We used RNA from 22 samples that included 10 tumor biopsies from habits-associated cancers and 12 from non-habits associated cancers.

first: Radhakrishna

middle: M

last: Pillai

first: Janki

last: Babu


title: Qualitative modeling identifies IL-11 as a novel regulator in maintaining self-renewal in human pluripotent stem cells

status: Public on Sep 26 2013

city: Berlin

first: Raed

last: Abu Dawud

address: Föhrertstr. 15

department: Immunology

institute: Berlin-Brandenburg Center for Regenerative Therapies

summary: A systems biology approach in which qualitative modeling based on combining boolean networks and in silico perturbation experiments were employed to identify 15 pluripotency regulating cytokines or cytokine related genes. IL-11 was validated as a novel factor capable of maintaing the undifferentiated state of human embryonic stem cells in the absence of exogenously added bFGF to the culture acting via a different mechanims than bFGF.

overall_design: Transcriptomic microarray data of eight overexpression and knock-down experiments were used for qualitative modeling based on boolean networks to predict novel factors - mainly cytokines - that maintain pluripotent human embryonic stem cells in the absence of bFGF in culture. The culture was maintained for at least 9 passages using and stained positive for alcaline phosphatase staining, OCT3/4, SOX2, NANOG, TRA1-60. Microarray based gene expression profiling showed that the IL-11 treatment occupies an intermediate state, between bFGF treatment and the negative control which is no cytokine treatment as judged by hierarchical clustering. Moreover, KEGG pathway analysis indicates common and additional distinct mechanisms of bFGF and IL-11 dependant pluripotency dependant mechanisms.

first: Hedi

last: Peterson

first: Abhishek

last: Garg

first: Ying

last: Wang

first: Jaak

last: Vilo

first: Ioannis

last: Xenarios

first: James

last: Adjaye


title: Genotype-by-diet interaction effects on transcriptome profiles in Drosophila melanogaster

status: Public on Sep 19 2013

city: Tuscaloosa

first: Laura

middle: Katie

last: Reed

state: AL

address: 300 Hackberry Ln.

department: Biological Sciences

institute: University of Alabama

summary: This study was performed by testing 21 wildtype genetic lines on four different diets to look at the transcriptomic, metabolomic, and gross phenotype variation.  The diets used were Normal Cornmeal-molasses symbolized N, high sugar symbolized 4, high fat F, and control C a low sugar diet.  Larvae were raised from hatching to 3rd instar on the respecitve diets at a density of 50 larvae per food vial.  Larvae were then collected for metabolomics, transcriptomic, and gross phenotype measurements (e.g. trehalose concentration, triglyceride concentration).  Samples for transcriptomic and metabolomic analyses were snap frozen in liquid nitrogen.

overall_design: 236 total samples were analyzed.  In most cases the are unique technical replicates except in the cases where the line, diet, and biological replicate characterists are identical.


title: Expression data from rat spinal cord injury and mesenchymal stromal cells (MSC) or olfactory ensheathing cells (OEC) transplantation

status: Public on Oct 16 2013

city: Bellaterra

first: Xavier

last: Navarro

address: Edif. M, Campus UAB

country: Spain

institute: Univarsitat Autònoma de Barcelona

summary: We analyzed the changes in the spinal cord transcriptome after a spinal cord contusion injury and MSC or OEC transplantation. The cells were injected immediately or 7 days after the injury. The mRNA of the spinal cord injured segment was extracted and analyzed by microarray at 2 and 7 days after cell grafting.

overall_design: 52 total samples were analyzed in 13 different groups. Each group include 4 samples and each one were analyzed as a biological replica. The intact animals were used as control of injury. The vehicle (VHC) groups were used as control of transplantation procedure. The MSC or OEC graft were injected at the day of injury (acute graft) or seven days after injury (delayed graft). The samples from engrafted animals were obtained at 2 or 7 days after cell transplantation. To determine the effects of MSC or OEC transplantation, the expression value of each engrafted sample were compared with correspondent VHC group.

first: Abel

last: Torres-Espín

first: Joaquim

last: Hernández


title: Limited effects of an eIF2αS51A allele on neurological impairments in the 5xFAD mouse model of Alzheimer’s disease

status: Public on Sep 10 2013

city: Bonn

first: Dan

last: Ehninger

state: NRW

address: Ludwig-Erhard-Allee 2

institute: German Center for Neurodegenerative Diseases (DZNE)

summary:
Transcriptome analysis of hippocampal RNA samples from wild-type, 5xFAD, 5xFAD;eIF2α+/S51A and eIF2α+/S51A mice
Our transcriptome analyses showed clear transcriptional alterations in hippocampi of 5xFAD compared to wild type mice that were not corrected by the eIF2αS51A allele.

overall_design:
Hemizygous 5xFAD mice, which were on a genetic background of B6/SJL, were crossed with eIF2α+/S51A mice (C57BL/6J background), to generate the offspring that was analyzed in the microarray.
Hippocampal samples of 12 mice (4 groups: wild-type, 5xFAD, 5xFAD;eIF2α+/S51A and eIF2α+/S51A) were processed using Affymetrix Mouse Exon 1.0 ST platform. Array data was processed by Affymetrix Exon Array Computational Tool. No technical replicates were performed.

first: Katharina

last: Paesler

first: Moritz

last: Hettich

first: Magdalena

last: Siwek

first: Devon

last: Ryan

first: Susanne

last: Schröder

first: Anna

last: Papazoglou

first: Karl

last: Broich

first: Ralf

last: Müller

first: Astrid

last: Becker

first: Alexander

last: Garthe

first: Gerd

last: Kempermann

first: Marco

last: Weiergräber


title: HIF1alpha drives early induction of pluripotency through reprogramming of glycolytic metabolism

status: Public on Oct 01 2013

first: Alessandro

last: Prigione

state: Berlin

address: Robert-Roessle-Str. 10

institute: Max Delbrueck Center for Molecular Medicine

summary: Gene expression analyis of two neonatal fibroblasts (BJ and HFF1), one adult dermal fibroblasts (NFH2), two BJ-derived human iPSCs (iB4 and iB5), two HFF1-derived iPSCs (iPS 2 and iPS4), four NFH2-derived iPSCs (OiPS3, OiPS6, OiPS8, OiPS16), one amniotic fluid cells and three derived iPSCs (lines 4, 5, 6, 10, and 41), two human ES cells (H1 and H9), neonatal fibroblasts transduced with the four retroviral factors (OKSM) after 24h, 48h, and 72h, neonatal fibroblasts treated with EDHB for 24h, 48h, and 72h, neonatal fibroblasts transduced with four factors and treated with EDHB for 24h, 48h, and 72h, neonatal fibroblasts knocked down for HIF1A (HIF1-KD) and for a scrambled sequence (SCR-KD)

overall_design: Total mRNA obtained from somatic cells (fibroblasts and amniotic fluid cells), pluripotent stem cells (iPSCs and hESCs), and somatic cells exposed to HIF1A activation or HIF1A suppsression in addition to the standard retroviral-based reprogramming.


title: The human cap-binding complex is functionally connected to the nuclear RNA exosome

status: Public on Nov 08 2013

city: Montpellier

first: Edouard

last: BERTRAND

address: 1919 Route de Mendes

institute: CNRS

summary: Nuclear processing and quality control of eukaryotic RNA is mediated by the multi-subunit RNA exosome, which utilizes accessory factors to regulate its enzymatic activity. However, the mechanism of exosome recruitment to its ribonucleoprotein (RNP) targets remains poorly understood. Here we disclose a physical link between the human nuclear RNA exosome and the cap-binding complex (CBC). The CBC associates with the ARS2 protein to form CBC-ARS2 (CBCA), and then further connects together with the uncharacterized ZC3H18/NHN1 protein to the nuclear exosome targeting (NEXT) complex, forming CBC-NEXT (CBCN). RNA immunoprecipitation analysis using CBCN factors as baits as well as the combinatorial depletion of CBCN and exosome components underscore the functional relevance of CBC-exosome bridging at the level of target RNA. Specifically, CBCA suppresses read-through transcription of several RNA families by promoting their transcriptional termination. We suggest that the RNP 5’cap links transcription termination to exosomal RNA degradation via CBCN.

overall_design:
In total 10 samples; 4 control IP HeLa, 2 Flag- Ars2 IP,  2 Flag-CBP20 IP; and 2 GFP-RBM7 Ips.
The signal intensity data was analyzed with the Affymetrix Tiling Analysis Software (v. 1.1) using parameters: one side upper, 90 bp bandwidth and perfect match only. Output txt files (i.e. result file).
TASParam* files include parameter settings and input file information for the TAS analysis for each result file.
The description of 'ProcessedDatas_TA.xls' file is provided in the 'README.txt'

first: Peter

middle: R

last: Andersen

first: Michal

last: Domanski

first: Maiken

middle: S

last: Kristiansen

first: Helena

last: Stirvall

first: Evgenia

last: Nitni

first: Céline

last: Verheggen

first: Jakob

last: Bunkerborg

first: Ina

last: Poser

first: Marie

last: Hallais

first: Rickard

last: Sandberg

first: Anthony

last: Hyman

first: John

last: LaCava

first: Michael

last: Rout

first: Jen

last: Bertrand

first: Torben

last: Jensen


title: Expression data of mammary epithelial cells during the epithelial-mesenchymal transition

status: Public on Sep 09 2013

city: Cambridge

first: Wai Leong

last: Tam

address: 9 Cambridge Center

country: USA

institute: Whitehead Institute

summary: The EMT program allows epithelial cells to become endowed with motility, invasiveness and stem cell traits. We investigated difference in signaling networks that are differentially utilized in EMTed and non-EMTed cells, thereby identifying therapeutic targets that are unique to EMT/cancer stem cells.

overall_design: We expressed the EMT transcription factors, Twist, Snail and Slug in HMLE human mammary epithelial cells, and compared their gene expression with parental cells. We identified kinases that are more differentially regulated between the epithelial and mesenchymal cell state.

first: Wai


title: Cytokine-induced changes in the gene expression profile of human cerebral microvascular endothelial cell-line, hCMEC/D3

status: Public on Sep 16 2013

city: La Jolla

first: Miguel

middle: Alejandro

last: Lopez-Ramirez

state: California/San Diego

address: 9500 Gilman Drive

department: School of Medicine

institute: University of California, San Diego

summary: In the current study, we aimed to investigate the gene expression pattern in hCMEC/D3 cells using mRNA microarray analysis and to establish wheather hCMEC/D3 cells are a suitable in vitro human BBB model of neuroinflammation.

overall_design: To identify the major molecular process involved in cytokine-induced changes in brain endothelial phenotypic characteristics and subsequently function, we analysed changes in mRNA expression profile after activation of hCMEC/D3 cells by TNFa and IFNg and results were contrasted to unstimulated cells. hCMEC/D3 cells were grown on collagen-coated six-well plates and treated with 10 ng/ml of TNFa and IFNg (R&D systems, Abingdon, Oxon, UK) for 24 h

first: Basil

last: Sharrack

first: David

middle: K

last: Male

first: Ignacio

last: Romero


title: Alterations in mRNA levels in the dentate gyrus in epileptic rats

status: Public on Aug 14 2013

city: Warsaw

first: Katarzyna

last: Lukasiuk

address: 3 Pasteur Street

department: Department of Molecular and Cellular Neurobiology

country: Poland

institute: Nencki Institute of Experimental Biology Polish Academy of Sciences

summary: Analysis of the dentate gyrus of amygdala electrical stimulation model of temporal lobe epilepsy. Results provide insight into the molecular mechanism underlying epileptogenesis.

overall_design: This study was designed to estimate changes in gene expression levels after 7 and 30 days after electrical stimulation of amygdala as a model of temporal lobe epilepsy. The advantage of this study is time matched control (sham operated animals sacrificed at the same age as stimulated animals).

first: Anna

last: Bot

first: Konrad

middle: J

last: Debski


title: Dentate gyrus in epileptic rats

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

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

overall_design: Refer to individual Series


title: Identification of neural stem cell gene expression signatures associated with disease progression in alveolar soft part sarcoma by integrated molecular profiling [aCGH]

status: Public on Jul 30 2013

city: Iowa City

first: Ramakrishna

last: Sompallae

state: IA

address: 285 Newton Road, 5292 CBRB

department: Iowa Institute of Human Genetics

institute: University of Iowa

summary: Alveolar soft part sarcoma (ASPS) is a soft tissue sarcoma with poor prognosis.  Apart from the recurrent, non-reciprocal t(X,17)(p11.2;q25) translocation, there is little molecular evidence for the origin, initiation and progression of this cancer. We analysed 16 primary and metastatic ASPS samples to elucidate candidate molecular pathways involved in tumor pathogenesis. FISH analysis identified the ASPL-TFE3 fusion in all cases. High-resolution aCGH revealed a higher number of numerical aberrations in metastatic tumors relative to primaries, but failed to identify any consistent alterations in either group. Gene expression analysis highlighted 1,063 genes which were differentially expressed between primary and metastatic tumors. Gene set enrichment analysis identified 16 enriched genesets (p < 0.1) associated with differentially expressed genes. Notable among these were several stem cell gene expression signatures and pathways related to differentiation.  In particular, the paired box transcription factor PAX6 was up-regulated in the primary tumors, along with several genes whose mouse orthologs have previously been implicated in Pax6-DNA binding during neural stem cell differentiation. In addition to suggesting a neural origin for ASPS, these results implicate transcriptional deregulation from fusion genes in the pathogenesis of ASPS, rather than extensive chromosomal instability.

overall_design: 15 different tumor and normal paired samples were analysed

first: Shamini

last: Selvarajah

first: Pyne

last: Saumyadipta

first: Eleanor

last: Chen

first: Azra

last: Ligon

first: Petur

last: Nielsen

first: Glenn

last: Dranoff

first: Edward

last: Stack

first: Massimo

last: Loda

first: Richard

last: Flavin


title: Methylation profiles of MCF-10A cells infected with MBD2 lentivirus

status: Public on Jun 13 2013

first: Moshe

last: Szyf

address: McIntyre Medical Building, 3655 Promenade Sir William Osler, Room 1309

department: Pharmacology

country: Canada

summary: Methylated DNA binding protein 2 (MBD2) has been shown to bind specific methylated promoters and suppress transcription. Here we systematically investigate MBD2 suppression by overexpressing MBD2 in MCF-10A cells and generating genome-wide promoter methylation profiles in order to identify methylation changes likely to affect gene expression levels.

overall_design: MCF-10A cells were infected with MBD2 lentivirus in order to increase MBD2 expression. DNA was extracted from both infected and non-infected cells and enriched for methylated DNA through the method of methylated DNA immunoprecipitation (MeDIP). Enriched and total DNA was hybridized in different channels to 244K custom microarrays (Agilent Technologies) that contained probes covering at 100bp-spacing all transcription start sites from -800bp to 200bp (human, Ensembl v44) and all microRNAs in miRBase from 250bp before to 250bp after the microRNA. Three technical replicates were hybridized for infected and non-infected cells.

first: Sebastian

last: Alvarado

first: Johanne

last: Wyglinski

first: Matthew

last: Suderman

first: Stephen

last: Andrews


title: Gene expression changes in breast epithelial cells surviving treatment with TRAIL (TNF-Related Apoptosis Inducing Ligand)

status: Public on Jul 15 2013

city: Boston

first: Deborah

last: Flusberg

state: MA

address: 200 Longwood Ave

department: Systems Biology

institute: Harvard University

summary: In this study, we subjected the phenomenon of fractional killing in a clonal population of TRAIL-sensitive cells to careful analysis. We asked whether cells that survive initial exposure to TRAIL are sensitive or resistant to subsequent treatment with TRAIL or other apoptosis-inducing agents.  We observed that TRAIL survivor cells were highly resistant to a subsequent treatment with TRAIL 24hr later but that this resistance disappeared following several days in culture. Resistance did not involve downregulation of TRAIL receptors and extended to death ligands that bind different classes of receptors: TRAIL survivors were transiently resistant to FasL and vice versa.  Gene expression analysis revealed that NF-kB-mediated inflammatory genes were activated in transiently resistant survivor cells leading to an inflammatory phenotype, but resistance was mediated by an independent mechanism related to changes in signaling at the DISC.  Periodic exposure to TRAIL sustained resistance, demonstrating a component of induced survival signaling leading to transient acquired resistance to TRAIL.  Based on these results we propose that TRAIL treatment leads to a transient adaptation in survivor cells that can be sustained in cells exposed to long-term TRAIL treatments, leading to acquired resistance.  Minimizing the impact of cell-to-cell variability on TRAIL-mediated killing will thus require appropriate spacing of stimuli as well as the use of additional agents that inhibit pro-survival pathways.

overall_design:
RNA was collected from Control (untreated) MCF10A cells, Survivors of TRAIL treatment (Day 1), Reset cells (survivors on Day 7), and Repeat cells (Survivors treated with TRAIL on 2 subsequent days).
RNA was also collected from Control and Survivor MCF10A cells expressing an IKB-super-repressor construct (Addgene, Plasmid 15291; Boehm et al., 2007), or treated with caspase inhibitors.
Three biological experiments were performed (on different days) with 1-2 replicates of each sample collected for each experiment.  The total number of samples was 31, on 4 IlluminaRef8 BeadChips (one sample was from an unrelated experiment and was not included).  The number of total replicates for each treatment is as follows: Control (7); Survivors (6); Reset (3); Repeat (3); Control-IKB-super-repressor (2); Survivors-IKB-super-repressor (2); Control-zVADinhibitor (2); Survivors-zVADinhibitor (2); Control-IETDinhibitor (2); Survivors-IETDinhibitor (2).

first: Oliver

last: Hofmann

first: Charlie

last: Whitaker

first: Peter

last: Sorger