title: Inflammation, adenoma and cancer: objective classification of colon biopsy specimens with gene expression signature

status: Public on Oct 31 2007

first: Balazs

last: Györffy

address: Bókay 53

institute: Hungarian Academy of Sciences

summary:
Background and Aims: Gene expression analysis of colon biopsies using high-density oligonucleotide microarray can contribute to the understanding of local pathophysiological alterations and to functional classification of precancerous adenoma, different stage colorectal carcinomas (CRC) and inflammatory bowel diseases (IBD).

Results: Significant overexpression of collagen IV, lipocalin-2, caveolin-1, calumenin genes, and significant dowregulation of aquaporin-8, amnionless homolog, prostaglandin D2 receptor genes were detected in CRC patients compared to normal. Adenoma samples were characterized by upregulated CD44 antigen, met proto-oncogene and downregulated chemokine ligand-12, ADAM-like decysin-1 and ATP-binding casette A8 discriminatory genes. In IBD samples significantly increased lipocalin-2, interferon induced transmembrane protein 1 and 3 mRNA levels, decreased zinc finger protein 91 and transient receptor potential cation channel M6 mRNA levels were found. Ulcerative colitis and Crohn’s disease can be distinguished  according to the top five genes: cyclin-G2; tripartite motif-containing-31; TNFR shedding aminopeptidase regulator-1; C-type lectin superfamily member-14 and AMICA. 88.3-97.8% of  the cases was correctly classified according to discriminatory genes.

Conclusions: Our whole genomic microarray analysis of biopsy samples provides discriminative signatures, and an insight into pathophysiological background of colonic diseases. The results afford a data warehouse which can be further mined for in-depth pathway analyses.
Keywords: Colon biopsy specimens in diseased and normal state

overall_design: Total RNA was extracted, amplified and biotinylated from frozen colonic biopsies of 15 patients with CRC, 15 with adenoma, 15 with IBD and 8 healthy normal controls. Genome-wide gene expression profile was evaluated by HGU133 Plus 2.0 microarrays. Gene expression was also measured by real-time PCR.


title: Murine Acute Lung Injury

status: Public on Feb 02 2008

city: Binghamton

first: Eric

middle: P

last: Hoffman

state: NY

address: PO Box 6000

department: Pharmaceutical Sciences

country: USA

institute: Binghamton University - SUNY

summary:
With advances in supportive therapy in the last two decades, mortality rates from ALI/ARDS have improved somewhat, but remain around 30 to 40% with significant morbidity in survivors. Several promising treatments are in various stages of evaluation, but many have failed to prove beneficial in large randomized clinical trials (RCT). The first definitive step forward in ALI therapeutics occurred recently as a result of a large RCT demonstrating a mortality decrease from 40 to 31% with the use of low-volume ventilation strategies. From this, it is clear that the opportunity for successful intervention in ALI exists. However, therapeutic advances remain frustrated by the lack of complete understanding of ALI pathophysiology. This stresses the importance of integrating basic and clinical research of the molecular pathogenesis of this disease. The conclusions of a recent National Heart, Lung, and Blood Institute (NHLBI) Working Group on ALI support this type of research as a priority for future investigations of ALI. One of the areas of research given priority by this ALI Working Group is the issue of ALI severity progression and the role of cells of innate immunity in this process. Currently, the processes that determine which ALI patients progress to ARDS and which do not are unclear. As with many phenotype differences, there is most likely a genetic component involved. The basis for this has been demonstrated. For example, a surfactant protein B (SP-B) polymorphism appears to increase a patient’s risk of developing ALI from pneumonia. Additionally, a polymorphism in the promoter region of the gene for interleukin-6 (IL-6) has been associated with a poor prognosis in patients with ARDS. Understanding the intracellular processes of these genes and the cells expressing them in ALI progression could lead to the identification of molecular markers of ALI severity and eventually to the development of targeted therapies. An examination of genetically uniform animals will provide a clearer insight into the interaction between immune cells in ALI progression as well as guide future human experiments.
Keywords: Time Series Design, ALI - acute lung injury, ARDS - acute respiratory distress syndrome, CLP - cecal ligation and puncture

overall_design: Specific Aim 1. We will prospectively collect and bank RNA from peripheral blood CD4+ T lymphocytes (Th1 and Th2 subsets) and platelets from cecal ligation and puncture-treated BALB/c mice using a negative selection technique. Specific Aim 2. Four mice will undergo whole blood sampling at each of 3 time points (t = 0, 24, and 48 hours). Time 0 represents the point of CLP. Specific Aim 3. The temporal series of 3 cell types pooled within each time point will be expression profiled (3 time points x 3 cell types x MOE430A array = 9 profiles) in order to generate a map of potential cell-cell interactions and a prioritization model for examining these further.

first: Robert

last: Freishtat


title: Expression data from wildtype and gas-1 mitochondrial mutant C. elegans

status: Public on Feb 14 2008

city: Philadelphia

first: Marni

middle: J

last: Falk

state: PA

address: 3615 Civic Center Blvd

department: Pediatrics/ Human Genetics

institute: CHOP

summary:
Utilizing C. elegans as a model of mitochondrial dysfunction provides insight into cellular adaptations which occur as a consequence of genetic alterations causative of human disease.  We characterized genome-wide expression profiles of hypomorhpic C. elegans mutants in nuclear-encoded subunits of respiratory chain complexes I, II and III.
Our goal was to detect concordant changes among clusters of genes that comprise defined metabolic pathways utilizing gene set enrichment analysis.
Keywords: Wildtype vs mutant comparison as a method for studying contributors to disease processes

overall_design: 5 biological replicates of wildtype and electron transport chain (ETC) mutant C. elegans were used as sources of total RNA, each for hybridization to a single Affymetrix whole-genome microarray.  Comparison of the data was intended to reveal metabolic pathways downstream of the mutation.

first: Zhe

last: Zhang


title: VSartorelli SMC Calorie Restriction

status: Public on Dec 07 2007

summary:
The integration of positive and negative intra- and extra-cellular signals dictates whether a cell will proliferate or differentiate. While it is intuitive to speculate that nutrients availability may influence this alternative, a comprehensive complement of the molecular determinants involved in this process has not been elucidated yet. In this study, we will investigate how nutrients (glucose) affect skeletal myogenesis. C2C12 cells will be cultured in high glucose and low glucose conditions, and their differenciation will be studied.
Keywords: Differential Design, Differentiation Medium (DM), Growth Medium (GM)

overall_design: We hypothesize that calorie restriction may have an effect on appropriate differentiation of skeletal myoblasts and this effect can be demonstrated by expression profiling.

first: Vittorio

last: Sartorelli


title: FSHD Muscle Profiles

status: Public on Oct 23 2007

summary:
Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal dominant disorder linked to contractions of the D4Z4 repeat array in the subtelomeric region of chromosome 4q. By comparing genome-wide gene expression data from muscle biopsies of patients with FSHD to those of 11 other neuromuscular disorders, we intend to identify disease-specific changes which are more likely to be involved in the early stages of the disease progression.  The data will help to identify pathological mechanisms involved in FSHD.
Keywords: Differentiation design

overall_design: Comparison of the profiles of FSHD to 13 other conditions for disease-specific changes.  The 13 conditions are NHM (Normal healthy muscle) n=15; JDM (Juvenile dermatomyositis) n=25; HSP (Human spastic paraplegia) n=4; FSHD (facioscapulohumeral dystrophy) unaffected n=5, affected n=9; FKRP (Fukutin related protein deficiency) n=7; ED-L (Emery-Dreifuss muscular dystrophy, lamin A/C deficiency) n=4; ED-E (Emery-Dreifuss muscular dystrophy, emerin deficiency) n=4; DYSF (dysferlinopathy) n=10; DMD (Duchenne Muscular Dystrophy) n=10; CALP (Calpain-3 deficiency) n=10; BMD (Becker Muscular Dystrophy) n=5; AQM (Acute quadriplegic myopathy) n=5; ALS (Amyotrophic lateral sclerosis) n=9.

first: YiWen

last: Chen


title: Expression data in native lipoprotein-stimulated human THP-1 macrophages

status: Public on Sep 19 2007

city: COPENHAGEN

first: Silvio

last: Zaina

address: Blegdamsvej 9

department: Clinical Biochemistry

country: Denmark

institute: Rigshospitalet

summary:
We previously found that a native lipoprotein mix with a high VLDL+LDL/HDL ratio causes a global de novoDNA methylation in THP-1 macrophages. In the present experiment we assessed the consequences of global lipoprotein-induced de novo DNA methylation on global gene expression in the same cells. Moreover, we sought to use gene expression array data to measure RNA expression levels for candidate factors mediating the epigenetic effects of lipoproteins.
Keywords: comparison treated vs. control

overall_design: Human native VLDL, LDL and HDL lipoproteins were isolated from buffy coats, fractionated by ultracentrifugation, stored at -80deg., desalted to PBS before usage and kept at 4deg. for a maximum of 7d. THP-1 monocytes were differentiated to macrophages, stimulated for 24h with a mix of 68.8mg/ml VLDL, 32.1mg/ml LDL, 91.1mg/ml HDL or unstimulated (control), in serum-free medium with 2% BSA.  Three independently isolated lipoprotein samples were used in triplicate.

first: Charlotte

last: Schjering

first: Susanne

last: Smed


title: Transcriptional pathways associated with skeletal muscle disuse atrophy in humans

status: Public on Aug 28 2007

summary:
Disuse atrophy is a common clinical phenomenon which significantly impacts muscle function and activities of daily living. In this study, we did expression profiling to identify transcriptional pathways associated with muscle remodeling in a clinical model of disuse.
Keywords: Differentiation design

overall_design: 28 Skeletal muscle biopsies from the medial gastrocnemius in patients with an ankle fracture (4 patients, 8 profiles) and from healthy volunteers (2 subjects, 4 profiles) subjected to 4-11 days of mobilization, as well as from the non-immobilized contralateral legs (16 profiles).

first: Chen

last: Yiwen


title: Unique MicroRNA Expression Signature Predicts Survival, Metastases and Recurrence of HCC

status: Public on Jan 14 2008

city: Bethesda

first: Xin

middle: Wei

last: Wang

state: MD

address: 37 Convent Drive

department: Laboratory of Human Carcinogenesis

institute: National Cancer Institute

summary:
In this study we investigated the miRNA expression profile of Hepatocellular carcinoma (HCC) specimens from radical resection. We developed a unique 20 miRNA signature that could significantly distinguish HCC venous metastasis from metastasis-free HCC. In contrast to HCC staging systems, this signature was capable of predicting survival and recurrence of HCC patients with multinodular or solitary tumors, including those with early-stage disease. Moreover, the signature was an independent and significant predictor of patient prognosis and relapse when compared to other available clinical parameters. Our study suggests that these 20 miRNAs can enable HCC prognosis and may have clinical utility for the advance identification of HCC patients with a propensity towards metastasis/recurrence.
Keywords: disease state design

platform_organism:
Homo sapiens
Mus musculus

overall_design: Gene expression profiles were conducted in primary HCC and corresponding noncancerous hepatic tissues from 244 Chinese HCC patients. A total of 134 well-defined cases were used as a training group. Among them, 30 had primary HCC lesions accompanied by tumor emboli and 104 had solitary HCC with no metastasis/recurrence found at follow-up (3 yr). We used a testing group of 110 independent cases. The testing cases included 43 multinodular and 67 solitary HCC. In addition, eight normal liver tissues from disease-free patients were included as normal controls. In the analysis of the 244 HCC cases, RNA was isolated in a pairwise fashion from tumor or non-tumor tissue and samples were selected in random order for miRNA analysis to avoid grouping bias.


title: Myogenesis MyoD

status: Public on Dec 13 2006

summary:
The transcription factor MyoD can coax na?e fibroblasts or otherwise committed cells to adopt the skeletal muscle phenotype by activating the muscle gene expression program. Activation of muscle gene expression occurs in quantal steps with not all the target genes of MyoD being activated at the same time. Some genes are induced in the initial phases, others at later stages despite the fact that MyoD is present throughout the differentiation process. MyoD is post-translationally modified by phosphorylation, ubiquitination, and acetylation. Here, we have employed a model system in which MyoD and its non-acetylatable version were inducibly expressed in mouse embryonic fibroblasts derived from mice to investigate how MyoD acetylation may contribute to differential gene activation.
Keywords: Time-Series

overall_design: Mouse embryos fibroblasts (MEFs) obtained from MyoD-/-/Myf5-/- animals will be transduced with retroviruses expressing a estrogen receptor hormone binding domain fused to either mouse MyoD wild type (ER-MyoD wt) or MyoD bearing three point mutations at lysine residues 99, 102, and 104 that render it no longer acetylatable ( ER-MyoD RRR). A retrovirus without the ER-MyoD insert was also employed as negative control.</p> Aim 2. We will compare genome-wide expression profiling of MEFs transduced with either ER-MyoD wt or ER-MyoD RRR cultured in the presence of a medium that promotes skeletal muscle differentiation (DM) supplemented with beta-estradiol for 0, 6, 12, and 24 hours, respectively.

first: Sartorelli

last: Vittorio


title: Effects of methoxychlor (MXC) in male largemouth bass

status: Public on Sep 08 2008

city: Gainesville

first: Christopher

middle: Joseph

last: Martyniuk

state: FL

address: CEHT Mowry Road

department: Physiological Sciences

institute: UF

summary:
Male largemouth bass were injected with 25 mg/kg MXC and sacrificed after 48 hours; liver dissected and used for total RNA extraction

Keywords: Methoxychlor injection; single injection and time point

The organochlorine pesticide methoxychlor (MXC) (1,1,1-trichloro-2,2-bis(p-methoxyphenyl)ethane) has been used increasingly as an insecticide since the banning of DDT, the primary advantage being that MXC is rapidly metabolized and does not show high levels of bioaccumulation in non-target organisms.  However, studies have shown that MXC can be metabolized into additional metabolites, such as mono-demethylated 2-(p-hydroxyphenyl)-2-(p-methoxyphenyl)-1,1,1-trichloroethane (OH-MXC) and bis-demethylated 2,2-bis(p-hydroxyphenyl)-1,1,1-trichloroethane (HPTE), both of which are estrogenic in mammals. In addition, there is increased potential for disruptions to normal hepatic physiology (Schlenk et al., 1998; Stuchal et al., 2006).  The objectives of the present study were to study the hepatic genomic response in male largemouth bass to an i.p. injection of MXC.  We performed a microarray analysis on 25 mg/kg MXC 48 hour injection because there was a significant induction of ERα and ERβb mRNA in the liver which was comparable to a 48 hour 1 mg/kg injection of E2 (previous work done by Blum et al., 2008; Aquat Toxicol. 86(4), 459-469).  We chose the liver because of the significant role this tissue plays in detoxification of contaminants and due to the high capacity to produce vitellogenin in response to estrogenic chemicals.  We were also interested in comparing the genomic response of MXC to estradiol alone to identify putative candidate genes and pathways that may be specific to MXC and not due to direct estrogenic effects mediated via E2 receptors.

overall_design: Largemouth bass injected with single i.p. with 25 mg/kg methoxychlor; sacrificed 48 days later,liver tissue studied. 4 individual liver samples (control and treatment)

first: Dan

last: Spade

first: Jason

last: Blum

first: Nancy

middle: D

last: Denslow


title: Acute molecular responses to lengthening vs shortening muscle contractions

status: Public on Mar 27 2007

summary:
To help elucidate mechanistic differences between lengthening and shortening muscle contractions we compared changes in gene expression within 24 h of an acute bout of each type of contraction in the quadriceps. Three healthy young men performed shortening contractions with one leg while the contralateral leg performed lengthening contractions. Biopsies were taken from both legs before exercise, 3, 6, and 24 h afterwards. Expression profiling was performed using a custom-made Affymetrix MuscleChip containing probesets of approximately 3,300 known genes and ESTs expressed in skeletal muscle. We identified 49 genes differentially regulated between the lengthening and shortening contractions. Using unsupervised hierarchical clustering, we identified four distinct clusters, three of which corresponded to unique functional categories (protein synthesis, stress response/early growth, and sarcolemmal structure). The results suggest distinct molecular pathways as early as 3 h post exercise. The molecular differences might contribute to mechanisms underlying the physiological adaptations seen with training using the two modes of exercise.
Keywords: Time Series Design

overall_design: The hypothesis of the current study was that genes involved in hypertrophy will be differentially regulated between the two types of contractions.

first: Yiwen


title: Circadian regulation in rat skeletal muscle

status: Public on Sep 11 2007

first: Eric

summary:
In intact animals, time of drug administration may be an important factor influencing drug response. Our general goal seeks to incorporate circadian time into the study of corticosteroid regulated gene expression. This study is designed to examine fluctuations in gene expression in skeletal muscle within the 24 hour circadian cycle in normal animals. Circadian time is relevant to designing optimal corticosteroid dosing regimens. Since levels of endogenous steroid exhibit circadian fluctuations, it is our hypothesis that the expression of genes controlled by corticosteroids either directly or indirectly will also exhibit a circadian pattern in normal animals.
Keywords: time series design

overall_design: Our previous studies examined changes in gene expression in response to corticosteroid treatment in adrenalectomized animals, where endogenous glucocorticoids are absent. This study is designed to examine baseline patterns of gene expression in normal animals within a 24 hour cycle. This data will be used in conjunction with future studies involving treatment of animals with corticosteroids at defined times within the circadian cycle. Fifty-four male normal Wistar rats (250-350 g body weight) were housed in a strictly controlled stress free environment with light:dark cycles of 12 hr:12hr. Three animals were sacrificed at each of 18 selected time points within the 24 hour cycle. RNA was prepared from gastrocnemius muscles for gene arrays. Time point designations reflect time after lights on in hours.

first: Richard

last: Almon


title: Myositis

status: Public on Jul 21 2006

last: Hoffman

summary:
Idiopathic inflammatory myopathies (polymyositis and dermatomyositis) are heterogeneous group of muscle disorders of unknown etiology.The pathogenic pathways responsible for muscle fiber damage and dysfunction in myositis are not currently well defined. Identification of such pathways may help to design novel therapeutic interventions and also help to develop diagnostic tests.
Keywords: Development or differentiation design

overall_design: Muscle biopsies from a separate group of 5 adult untreated female dermatomyositis (PHM-DM samples) patients were profiled and compared to muscle tissue of normal human healthy volunteers (FSH-NHM samples) to define  molecular pathways in muscle of myositis patients. Confirm and map key pathway members to specific cell types in the muscle tissue of patients and controls using RT-PCR, Western blotting and Immunolocalization.

first: Nagaraju

last: Kanneboyina


title: Recovery of biological information under heterogeneous experimental conditions using subgroup standardization.

status: Public on Oct 20 2007

city: Taipei

first: Hsin-Chieh

last: Yao

address: 1,  Rd. Roosevelt,  Sec. 4

department: CHE

country: Taiwan

institute: National Taiwan University

summary:
Recovery of biological information (i.e. Breast tumor versus non-tumor part of breast) from microarray data under heterogeneous experimental conditions (Buffer1 versus Buffer2) using subgroup standardization.
Microarray is a useful tool for gene expression analysis and prediction. For a given disease, a microarray database may come from various sources   with different experimental setups, collected over time. This heterogeneity provides unnecessary complication in data analysis and, even worse,   given false classification in clustering. Therefore, it is practically important to provide a standard data treatment for microarray data from   heterogeneous experimental conditions. In this work, “subgroup standardization” is proposed to compensate technical heterogeneities (e.g., buffers,   time, machines etc.) in microarray experimental conditions. Provided with repetitive microarray experiments, over time and buffers, the results   indicate that the proposed approach can extract correct biological information in the presence of technical irregularities. Hierarchical clustering is   used to validate the effectiveness of the proposed approach.
Keywords: disease state study

overall_design: 98 of breast cancer specimens and 8 of non-tumor part of breast specimens were applied in the study.  All the signals from the mRNA profile of each sample in the microarrays were normalized using the internal control RNA- Stratagene's human common reference RNA.

first: Hsin

middle: C

first: Rajani

middle: K

last: Mudi

first: Cheng

last: Yu

first: Hsueh

middle: F

last: Juan

first: Hsiao

middle: W

first: Fon

last: Hsieh

first: Li

middle: Y

last: Chang

middle: L

last: Hwa

first: Wen

middle: H

last: Kuo

first: King

first: Yi

middle: S

last: Lin


title: Murine Spleen

status: Public on Jul 13 2006

summary:
This project investigates immune response differences in male and female during puberty.
Keywords: Time-Series

overall_design: The specific aim is to expression profile of mouse male and femail spleens at pre-puberty (3-4 week old), puberty (6-9 week old), and post-puberty (24-28 week old).


title: p68 SMC differentiation

summary:
This project investigates the function of p68/p72 in muscle gene expression and skeletal C2C12 cell differentiation. p68/p72 in C2C12 cells cultured in either growth medium (GM) or differentiation medium (DM) was knocked down using shRNA p68/p72 retrovirus, and globle gene expression was profiled using Affymetrix MOE 430A and 430B GeneChip.
Keywords: Time-Series

overall_design: The specific aim is to study muscle gene expression changes and skeletal muscle differenciation using RNA interference of p68/p72 in C2C12 cells.

first: Vittorio

last: Sartorelli


title: Spinal Cord Injury Murine Model

status: Public on Jul 12 2006

summary:
Traumatic spinal cord injury (SCI) initiates a complex series of pathophysiological secondary responses that lead to tissue loss and functional deficits.This study represents a comprehensive database of temporal changes in gene expression that underlie the secondary injury response that occurs in a well-defined mouse model of contusion injury.
Keywords: Time-Series

overall_design: Global changes in gene expression that contribute to secondary injury in a C57BL6 mouse model of contusion injury were evaluated using Affymetrix Mouse Genome 430 2.0 arrays.Mice were subjected to a moderate injury at the T8 spinal segment under isoflurane anesthesia.Sections of cord (0.4 cm in length) were analyzed from the site of impact and from the immediately adjacent rostral and caudal regions at 0.5, 4, 24, 72 h and 7 and 28 days after injury (n=3/per group), sham-injury (n=2 per group), or from naïve mice (n=2). Four mice were pooled for each individual n, for a total of 12 mice for each injury time point.

first: Alan

last: Faden


title: Murine EDMD

summary:
Study muscle regeneration in Emerin and Lamin AC KO mice. Gastrocnemius muscles were injected with cardiotoxin. Muscles were isolated at different time points.
Keywords: Time-Series

overall_design: The specific aim is to generate staged muscle degeneration/regeneration of Emerin deficient and Lamin A/C deficient mice. Muscles will then be express profiled using Affymetrix arrays.

first: Colin

last: Stewart


title: Gastric Bypass Human Obese Muscle

status: Public on Jun 20 2006

first: Eric

summary:
Obesity results from a chronic imbalance between energy intake and energy expenditure, with excess calories stored as fat. As such, weight loss has long been considered as a primary goal of treatment for obesity. A surgical treatment of severe obesity such as gastric bypass provides the most dramatic reductions in body weight, and a well-known effect of weight loss is an improvement in insulin sensitivity. However, the molecular mechanism underlying this association remains unclear. Thus, we profiled skeletal muscle of morbidly obese patients before and after gastric bypass surgery. Results from this project will provide global patterns of gene expression with weight loss, which help to understand the pathogenesis of obesity at the molecular level.
Keywords: Time-Series

overall_design: To identify responsive genes to weight loss.

first: Joseph

last: Houmard


title: 48h Immobilization in human

summary:
Our results suggest that 48h of immobilization increases expression of mRNA for components of the UPP and MT function while decreasing mRNA and protein for components involved in ECM integrity. We hypothesized that 48h of immobilization would increase gene expression and respective protein products for components of the ubiquitin proteasome pathway (UPP).
Keywords: stimulus or stress design

overall_design: To identify novel pathways involved in the atrophy program activated in response to 48h of limb immobilization in humans.

first: Priscilla

last: Clarkson


title: Similarities and differences in the transcriptome of human atherosclerotic and non-atherosclerotic macrophages

status: Public on May 31 2007

city: Amsterdam

first: Oscar

middle: Leonard

last: Volger

state: Noor Holland

address: Meibergdreef 15

department: Cardiology

country: Netherlands

institute: Academic Medical Center

summary:
Phenotypic and functional diversity between macrophage subpopulations reflects their plasticity to respond to microenvironmental signals. Apart from detecting differences in expression profiles, the comparison of the transcriptomes of different macrophage populations may also allow the definition of molecular similarities between these subsets.

Transcriptome analysis of human Kuppfer cells, alveolar, splenic and atherosclerotic plaque residing macrophages using microarrays, identified 42 genes that are specifically expressed in atherosclerotic plaque macrophages.

We also focus on the similarities in the transcriptome of human Kupffer cells, alveolar, splenic and atherosclerotic plaque residing macrophages. We hypothesized that these macrophages share a common expression signature. We performed microarray analysis on mRNA from these macrophage subsets (n = 4 patients) and developed a novel statistical method to identify genes with significantly similar expression levels. This method calculates the maximum difference in expression level of a gene, based on the estimated confidence interval on that genes expression variance. We listed the genes by equivalence ranking relative to their expression level. False Discovery Rate (FDR) estimation was used to determine significance. We identified 500 genes that had significantly equivalent expression levels in the macrophage subsets at an 5.5% FDR using a 90% confidence interval.  Equivalently expressed genes, identified by this newly developed method, may not only help to dissect common molecular mechanisms, but also to identify cell or condition specific sets of marker genes that can be used for drug targeting and molecular imaging.

overall_design:
Macrophages were isolated from N=4 tissues, being atherosclerotic plaques from carotid artery (CA), and from three none-atherosclerotic tissues, being lung (LU), spleen (SP), and liver (LI). This was done within four individual patients, defined as 275, 282, 288 and 289.
Each of the N=16 biological samples was hybridized in duplicate against a common reference RNA, resulting in a total of N=16 microarray hybridizations.

first: Wouter

last: Eijgelaar

first: Wanwisa

last: vD. Jamnongluk

first: Natasja

last: Kisters

first: Joost

middle: O

last: Fledderus

first: Erwin

last: Wijnands

first: Kitty

middle: B

last: Cleutjens

first: Johan

last: Kuiper

first: Anton

last: Horrevoets

first: Wim

last: Verhaegh

first: Ann-Pascale

last: Bijnens

first: Mat

last: Daemen


title: Response of multiple genes to a chronic dose of corticosteroids in rat muscles

status: Public on Jun 19 2006

last: Hoffman

summary:
Synthetic glucocorticoids are used therapeutically for a variety of conditions. Both the efficacy and toxicity of corticosteroids arise from their pharmacologically exaggerated effects on target and non-target tissues. For example, beneficial effects deriving from inhibition of the immune system are accompanied by toxic side effects that include hyperglycemia, dyslipidaemia, muscle wasting, fatty liver, and an increased risk of atherosclerosis. Our previous time series analyzing the gene expression responses following a single bolus dose of methylprednisolone (MPL) provided interesting insight into the genomic responses of liver, skeletal muscle and kidney to corticosteroids. One objective with such extensive gene array time series data is to cluster genes into groups with common mechanisms of regulation. These clusters can be used to construct biologically rational models of the cascade of events that result in broad systemic phenomena such as diabetes, with the ultimate aim of therapeutic intervention at specific steps within the cascade
Keywords: Time-Series

overall_design: We analyze the two time series profiles with the intent of seeking ways to use the two profiles in tandem for clustering. The acute profiles were generated by sacrificing animals following a single acute dose of MP [7]. The time points were: 0.25, 0.5, 0.75, 1, 2, 4, 5, 5.5, 6, 7, 8, 12, 18, 30, 48 and, 72 hours after dosing. The chronic profiles were generated by implanting Alzet mini-osmotic pumps with a constant flow rate [8, 9]. Animals were sacrificed at 6, 10, 13, 18, 24, 36, 48, 72, 96 and 168 hr following implantation.

first: Richard

last: Almon


title: Human breast tumor

status: Public on Jun 28 2006

city: Seattle

first: Chang-Kyu

last: Lee

state: WA

address: 401 Terry Ave N.

department: Informatics

institute: Rosetta Inpharmatics

summary:
subpopulation of breat cancer using gene expression data and clinical data
Keywords: breast cancer survival and metastasis analysis

overall_design: 311 dual channel gene expression data


title: Comparative profiling in 13 muscle disease groups

status: Public on Oct 14 2005

first: Eric

summary:
Summary:   Genetic disorders of muscle cause muscular dystrophy, and are some of the most common inborn errors of metabolism. Muscle also rapidly remodels in response to training and innervation. Muscle weakness and wasting is important in such conditions as aging, critical care medicine, space flight, and diabetes. Finally, muscle can also be used to investigate systemic defects, and the compensatory mechansisms invoked by cells to overcome biochemical and genetic abnormalities. Here, we provide a 13 group data set for comparative profiling of human skeletal muscle. Groups studied are: Normal human skeletal muscle, Acute quadriplegic myopathy (AQM; critical care myopathy), Juvenile dermatomyositis (JDM), Amyotophic lateral sclerosis (ALS), spastic paraplegia (SPG4; spastin), Fascioscapulohumeral muscular dystrophy (FSHD), Emery Dreifuss muscular dystrophy (both X linked recessive emerin form; autosomal dominant Lamin A/C form), Becker muscular dystrophy (partial loss of dystrophin), Duchenne muscular dystrophy (complete loss of dystrophin), Calpain 3 (LGMD2A), dysferlin (LGMD2B), FKRP (glycosylation defect; homozygous for a missense mutation). U133A and U133B microarrays are both available.
Hypothesis:   This data set is able to define biochemical pathways that are either specific for a disease group, or shared between disease groups. For example, this data set has been used to determine the biochemical pathway perturbations that are shared between the two different types of Emery Dreifuss muscular dystrophy (lamin A/C, and emerin).

Specific Aim:   The specific aim of this study is to determine the disease-specific transcriptional profiles of these 13 patient groups, and to determine if these expression fingerprints provide either pathophysiology or diagnostic information for these diseases. Some of the groups in this large data set have been reported previously using U95A microarrays, as follows:

Juvenile dermatomyositis (JDM): Tezak Z, Hoffman EP, Lutz JL, Fedczyna TO, Stephan D, Bremer EG, Krasnoselska-Riz I, Kumar A, Pachman LM. Gene expression profiling in DQA1*0501+ children with untreated dermatomyositis: a novel model of pathogenesis. J Immunol. 2002 Apr 15;168(8):4154-63.
PMID: 11937576

Duchenne muscular dystrophy (DMD) Chen YW, Zhao P, Borup R, Hoffman EP. Expression profiling in the muscular dystrophies: identification of novel aspects of molecular pathophysiology. J Cell Biol. 2000 Dec 11;151(6):1321-36. PMID: 11121445

Spastic paraplegia (SPG4, spastin): Molon A, Di Giovanni S, Chen YW, Clarkson PM, Angelini C, Pegoraro E, Hoffman EP. Large-scale disruption of microtubule pathways in morphologically normal human spastin muscle. Neurology. 2004 Apr 13;62(7):1097-104. PMID: 15079007

Acute quadriplegic myopathy (AQM): Di Giovanni S, Molon A, Broccolini A, Melcon G, Mirabella M, Hoffman EP, Servidei S. Constitutive activation of MAPK cascade in acute quadriplegic myopathy.
Ann Neurol. 2004 Feb;55(2):195-206. PMID: 14755723

Fascioscapulohumeral muscular dystrophy (FSHD): Winokur ST, Chen YW, Masny PS, Martin JH, Ehmsen JT, Tapscott SJ, van der Maarel SM, Hayashi Y, Flanigan KM. Expression profiling of FSHD muscle supports a defect in specific stages of myogenic differentiation. Hum Mol Genet. 2003 Nov 15;12(22):2895-907. Epub 2003 Sep 30. PMID: 14519683
Keywords: muscle disease comparison


title: Human Glioblastoma

status: Public on Aug 24 2005

summary:
Summary: Astrocytomas can be categorized as either low grade or high grade (glioblastoma). Low grade astrocytomas are not generally aggressive tumors whereas glioblastomas are and in turn have a high mortality rate. The purpose of this experiment is to identify genetic differences between the two types.

Hypothesis: There will be a difference in RNA expression between high grade and low grade tumors.

Specific Aim: To identify genes which make a tumor high grade or low grade
Keywords: disease, cancer grade

overall_design: Comparison of 8 high grade and 12 low grade tumors

first: Tobey

last: MacDonald


title: An integrated strategy for analyzing the unique developmental program of different myoblast subtypes

status: Public on Jan 01 2006

city: Brookline

first: Sung

middle: Eun

last: Choe

state: MA

address: 258 Harvard St #164

institute: Wyeth Research

summary:
An important but largely unmet challenge in understanding the mechanisms that govern formation of specific organs is to decipher the complex and dynamic genetic programs exhibited by the diversity of cell types within the tissue of interest.  Here, we use an integrated genetic, genomic and computational strategy to comprehensively determine the molecular identities of distinct myoblast subpopulations within the Drosophila embryonic mesoderm at the time that cell fates are initially specified.  A compendium of gene expression profiles was generated for primary mesodermal cells purified by flow cytometry from appropriately staged wild-type embryos and from twelve genotypes in which myogenesis was selectively and predictably perturbed.  A statistical meta-analysis of these pooled datasets—based on expected trends in gene expression and on the relative contribution of each genotype to the detection of known muscle genes—provisionally assigned hundreds of differentially expressed genes to particular myoblast subtypes.  Whole embryo in situ hybridizations were then used to validate the majority of these predictions, thereby enabling true positive detection rates to be estimated for the microarray data.  This combined analysis reveals that myoblasts exhibit much greater gene expression heterogeneity and overall complexity than was previously appreciated.  Moreover, it implicates the involvement of large numbers of uncharacterized, differentially expressed genes in myogenic specification and subsequent morphogenesis.  These findings also underscore a requirement for considerable regulatory specificity for generating diverse myoblast identities.  Finally, to illustrate how the developmental functions of newly identified myoblast genes can be efficiently surveyed, a rapid RNA interference assay that can be scored in living embryos was developed and applied to selected genes.  This integrated strategy for examining embryonic gene expression and function provides a substantially expanded framework for further studies of this model developmental system.
Keywords: repeat

overall_design: mesodermal cells were profiled in wild type and mutant embryos

first: Beatriz

last: Estrada

middle: E

first: Stephen

last: Gisselbrecht

first: Sebastien

last: Michaud

first: Lakshmi

last: Raj

first: Brian

last: Busser

first: Marc

last: Halfon

first: George

middle: M

last: Church

first: Alan

last: Michelson


title: Murine Airway Hyperresponsiveness

middle: P

summary:
This project investigates the mechanisms that underlie asthma-related phenotypes associated with allergen exposure. See http://www.hopkins-genomics.org/asthma/asthma006/index.html

The goal of the experiment was to identify genes that change their levels of expression as a consequence of challenge with allergen. The experiments utilized a murine model of human asthma that employed BALB/CJ mice. In this particular sensitization-challenge protocol, the response produced by BALB/CJ mice is representative of a majority of the mouse strains tested. The antigen complex used to sensitize and challenge the mice was ragweed pollen an allergen that is highly relevant to human disease.
Keywords: time series, allergen

overall_design: 40 samples: 2 time points, 2 strains, allergen and PBS control

first: Marsha

last: Wills-Karp


title: Human Airway Hyperresponsiveness

summary:
The purpose of this project is to gain a better understanding of the early cytokine-mediated mechanisms that lead to asthma.
Keywords: time series, IL13

overall_design: 15 samples, 4 time points, 2 conditions.

last: Scott


title: acute genes during CNS injury and their expression in cultured astrocytes

status: Public on Jul 01 2005

city: Memphis

first: Eldon

last: Geisert

state: TN

address: 855 Monroe Avenue

department: Ophthalmology

institute: University of Tennesse

summary:
A robust set of CNS transcript changes was defined by comparing microarray data that describe the injury response of the rat retina [Vazquez-Chona et al., IOVS 2004; GSE1001], brain [Matzilevich et al., J Neurosci Res 2002; GSE1911], and spinal cord [Di Giovanni et al., Ann Neurol 2003; GDS63]. We determined the CNS injury genes that were expressed in cultured astrocytes from rat cortex [GSM34300] and from human optic nerve head [Yang et al., Physiol Genomics 2004; GDS532].
Keywords: other

sample_organism:
Homo sapiens
Rattus norvegicus

platform_organism:
Homo sapiens
Rattus norvegicus

first: Ping

last: Yang

first: Olga

last: Agapova

first: Amy

last: Parker

first: William

last: Shannon

first: Paula

last: Pecen

first: Jill

last: Duncan

first: Mercedes

last: Salvador-Silva

first: M

middle: R

last: Hernandez

first: Alen

last: Faden

first: Felix

last: Vazquez-Chona

first: Anthony

middle: N

last: Moore

first: Pramod

last: Dash


title: Neuromuscular Junction

status: Public on Mar 10 2005

first: Eric

last: Hoffman

summary:
NMJ Junction various time points normal C57BL10 LCM mRNA
Keywords: other


title: Murine Rat Brain Injury

summary:
Summary: Brain trauma is a major cause of morbidity and mortality, both in adult and pediatric populations. Much of the functional deficit derives from delayed cell death resulting from induction of neurotoxic factors that overwhelm endogenous neuroprotective responses.
Hypothesis: Gene expression profiling across species and models may help identify candidate molecular pathways induced by brain injury, some of which may provide novel targets for therapeutic intervention.
Specific Aim: To identify the potential molecular mechanisms underlying such delayed responses, we compared gene expression patterns using high-density oligonucleotide arrays at 4, 8, 24 and 72 hours after moderate levels of lateral fluid percussion-induced brain injury in rats and lateral controlled cortical impact injury in mice.

Keywords: other

sample_organism:
Mus musculus
Rattus norvegicus

platform_organism:
Mus musculus
Rattus norvegicus

first: JoAnne

last: Natale


title: Human Cystic Fibrosis

summary:
Summary: CF patients homozygous for the DF08 DF08 genotype present a full range of phenotypic manifestations that exist within the pulmonary system. This project aims to identify candidate genes that influence the severity of pulmonary disease
Hypothesis: The goal is to find genes predictive of progression in CF. More information can be found at http://www.hopkins-genomics.org/cf/cf001/index.html

Keywords: other

first: Mike

last: Boyle


title: Murine Spastic Spinal Cord

status: Public on Sep 28 2004

summary:
Summary:
We build a model for the molecular and cellular events underlying phenotypic discordance in glycine receptor defects (beta subunit). Some mice progress and die, while their littermates recover and get better, despite the same mutation on an inbred genetic background. We find evidence for glycine neurotransmitter toxicity and loss of glycinergic interneurons early in the disease, but some mice are able to keep things going until they can over-express homomeric alpha1 channels, whereupon they recover. In the mice progressing towards lethality, neurotransmitter toxicity too quickly extends to GABAergic interneurons and motorneurons, and they lose their window of time to upregulate the alpha1 glycine receptor, and they crash and burn. Importantly, human patients with glycine receptor defects typically show a resolution of their phenotype with age, and we propose that the same remodeling events are occuring in human patients.

Hypothesis:
Our data suggests that functional recovery of GlyRb mutant mice is likely due to expression of homomeric glycine receptors, rescue from excitotoxicity, and subsequent neuronal remodeling. We propose that human patients with hyperekplexia (mutations of glycine receptors) show remodeling similar to that of the recovering spastic mice, as human patients also show a lessening of symptoms as a function of age.

Specific Aim:
Murine models for human Startle Disease show clinical variability between littermates. Here, we determined the molecular remodeling of spastic GlyRb mutant spinal cord through the course of the disease, and develop a model for clinical disparity between littermates. At young ages, all animals were spastic, showed loss of glycine receptors, increased expression of vesicular glycine/GABA transporter and NMDA receptors, induction of activated caspase3, and preferential loss of glycinergic interneurons consistent with neurotransmitter toxicity model. Those littermates that recovered from symptoms showed strong over-expression of the GlyRa1 subunit, and increased myelination and synaptic plasticity. Littermates that showed a deteriorating clinical course failed to over-express GlyRa1, and also showed relative loss of gephyrin. These molecular changes were associated with preferential loss of GABAergic interneurons, and extensive motorneuron loss.
Keywords: other


title: SHR and WKY rat adrenal glands

status: Public on Nov 02 2004

city: La Jolla

first: Ryan

last: Friese

state: CA

institute: University of California San Diego

summary:
We measured gene expression in the adrenal glands of the Spontaneously Hypertensive Rat (SHR) and Wistar-Kyoto rat (WKY) using Affymetrix RG-U34A GeneChips. All rats were aged-matched at 4-weeks. The rats were obtained from the colonies at the Univeristy of California San Diego, La Jolla, CA.
Keywords: other

first: Payam

last: Mahboubi

first: Nitish

last: Mahapatra

first: Sushil

last: Mahata

first: Morton

last: Printz

first: Nicholas

middle: J

last: Schork

first: Geert

last: Schmid-Schonbein

first: Daniel

middle: T

last: O'Connor


title: Macular Degeneration

status: Public on Sep 02 2004

summary:
Age-related macular degeneration has a strong epidemiological association with cardiovascular disease. One pathogenic hypothesis that applies to both diseases is the concept of an abnormal cellular response to injury resulting in a disease phenotype. It has been hypothesized that this phenotype is also present in dermal fibroblasts. This study tests this hypothesis by examination of the expression profiles of fibroblasts obtained from diseased patients and subjected to sublethal cell injury.
Keywords: other

first: K

last: Csaky


title: Skeletal muscle cell differentiation

status: Public on Nov 18 2004

summary:
Skeletal muscle C2C12 cells were treated with or without trichostatin A (TSA), which induces differentiation. Total RNA was extracted and profiled at 5 time points after induction of differentiation (0, 4h, 12h, 24h, 48h).
Keywords: other

first: Vittorio

last: Sartorelli


title: Spinal Cord Trauma Supraspinal Tracts

status: Public on Feb 11 2005

summary:
Summary: Spinal cord injury (SCI) is a damage to the spinal cord induced by trauma or disease resulting in a loss of mobility or feeling. SCI is characterized by a primary mechanical injury followed by a secondary injury in which several molecular events are altered in the spinal cord often resulting in loss of neuronal function. Analysis of the areas directly (spinal cord) and indirectly (raphe and sensorimotor cortex) affected by injury will help understanding mechanisms of SCI.

Hypothesis: Areas of the brain primarily affected by spinal cord injury are the Raphe and the Sensorimotor cortex thus gene expression profiling these two areas might contribute understanding the mechanisms of spinal cord injury.

Specific Aim: The project aims at finding significantly altered genes in the Raphe and Sensorimotor cortex following an induced moderate spinal cord injury in T9.
Keywords: other

first: Alan

last: Faden


title: PGA Murine Lung Estrogen

status: Public on Apr 14 2004

summary:
Estrogen rescues the loss of gas exchange units in ovariectomized mice. This project studies the mechanisms of this rescue in ovariectomized mice treated with or without estrogen.
Keywords: other

first: Donald

last: Massaro


title: Hereditary Spastic Paraparesis

summary:
The goal of this project is to study differentially expressed genes in patients affected by Hereditary Spastic Paraplegia (HSP) linked to mutations of the gene encoding spastin an ubiquitously expressed protein that has recently been shown to be involved in microtubule regulation and vesicle trafficking by cell culture studies. Gene profiling was done with Affymetrix U95Av2 GeneChips using the total RNA extracted from muscle biopsies of 3 SPG4-linked HSP patients.
Keywords: other


title: Rat Kidney Methylprednisolone

summary:
Summary: To identify distinct temporal patterns of mRNA expression in the kidney of rats following a bolus dose of the corticosteroid methylprednisolone.
Hypothesis: That prednisone pharmacodynamics can be derived from expression profiling data.
Keywords: other

first: Richard

last: Almon


title: Murine Neurofibromatosis

status: Public on Jun 17 2004

summary:
Neurofibromatosis 1 (NF1) is a genetic, neurocutaneous syndrome caused by a mutation in the gene encoding neurofibromin. Individuals with NF1 develop growths that define the NF1 phenotype, including Lisch nodules, cafe-au-lait spots, and neurofibromas. However, more than 50% of individuals with NF1 have cognitive deficits, such as learning disorders and attention deficit/hyperactive disorder that are neuroanatomically unrelated to the neurofibromas.

The purpose of this study is to determine the molecular basis of the neurodevelopmental changes that result from the primary gene mutation using a mouse model of NF. These mice are heterozygous for the Nf1 gene (NF+/-), and develop learning and memory difficulties that mimic humans, but do not develop tumors.

By applying the technique of gene expression profiling to both NF+/- and control mice, we expect get a "genetic fingerprint" of 12,000 RNA molecules expressed in different parts of the brain during development. Comparison of the "genetic fingerprints" in these mice during development may help us identify key molecular changes that eventually result in cognitive deficits. Such an understanding of the molecular changes triggered by the primary gene mutation may eventually lead to treatments that prevent the cognitive deficits in NF1.
Keywords: other

first: D

last: Stephan


title: PGA Murine IL-13 Asthma

first: Eric

last: Hoffman

summary:
The IL-13 is a central mediator of allergic asthma. This project investigates the mechanisms by which IL-13 elicits the symptoms of asthma.
Keywords: other

first: Marsha

last: Wills-Karp


title: Gene expression profiling in DQA1*0501+ children with untreated dermatomyositis

status: Public on Jul 16 2003

summary:
Juvenile dermatomyositis (JDM), the most common pediatric inflammatory myopathy, is a systemic vasculopathy affecting young children. Epidemiology studies documenting an antecedent illness in the 3 mo before the first definite symptom (rash and/or weakness) of JDM are supported by immunologic data that suggest that the disease pathophysiology is Ag driven. The purpose of this study was to compare the gene expression profiles in muscle biopsies of four untreated DQA1*0501(+) JDM children with profiles from children with a known necrotizing myopathy (Duchenne muscular dystrophy), as well as an in vitro antiviral model (NF90), and healthy pediatric controls. Nearly half (47%) of the dysregulated genes in JDM were associated with the immune response. In particular, increased expression of IFN-alphabeta-inducible genes 6-16, myxovirus resistance protein p78, latent cytosolic transcription factor, LMP2, and TAP1 was observed. This profile is consistent with an IFN-alphabeta transcription cascade seen in the in vitro viral resistance model. The IFN-alphabeta-inducible profile was superimposed on transcription profiles reflective of myofiber necrosis and regeneration shared with Duchenne muscular dystrophy. Expressed genes were confirmed by quantitative real-time PCR (6-16), immunofluorescence (thrombospondin 4), and immunolocalization (IFN-gamma, p21).
Keywords: other

first: Z

last: Tezak

first: E

first: J

last: Lutz

first: T

last: Fedczyna

middle: G

last: Bremer

first: I

last: Krasnoselska-Riz

first: A

last: Kumar

first: L

last: Pachman


title: NINDS Rat Hippocampus Seizures

status: Public on Mar 29 2004

summary:
This study aims to investigate age-specific, time-dependent changes in gene expression that may underlie the priming effect of early-life seizures by looking at the sequence of gene expression patterns in the hippocampus at various times following Kainate induced seizures at postnatal day (P) 15.
Keywords: other

first: Sooky

last: Koh


title: NINDS Rat Neuron Parkinsons

summary:
The cardinal clinical features of Parkinson's disease result from selective loss of midbrain dopaminergic neurons.  The goal of this experiment is to determine the gene expression profiles of these neurons by studying untreated rat substantia nigra pars compacta (SNc) and ventral tegmental area (VTA) dopaminergic neurons using laser capture microscopy to obtain region-specific neuronal mRNA.

WARNING: These data are identical to those represented in GEO Series GSE1837.

first: Jim

last: Greene


title: NINDS Rat Epilepsy Diet

summary:
The ketogenic diet (KD) is an anticonvulsant treatment that has been used to manage medically-intractable epilepsies.  The KD requires 10-12 days to become maximally effective, suggesting that changes in gene expression are involved in its anticonvulsant action.  Using the Affymetrix rat arrays (RAE230A), 6 control samples and 5 KD samples were run.
Keywords: other

first: Ray

last: Dingledine


title: Hyperoxic lung injury

summary:
Nrf2 is a transcription factor that binds to antioxidant response elements of the regulatory region of a number of antioxidant genes.  A mutation in the Nrf2 gene increases susceptibility to hyperoxic lung injury.  This project examines expression differences between wild type and Nrf2 knock out mice with the hope of providing insight to the downstream effector genes regulated by Nrf2.
Keywords: other

first: Stephan

last: Kleeberger


title: Effect of prostaglandin analogs on aqueous humor outflow

summary:
The purpose of this study is to discover genes that might increase aqueous humor outflow when human ciliary muscle or human trabecular meshwork cells are treated with the prostaglandin analogues latanoprost free acid or prostaglandin F2alpha. Five tissue donors were pooled on each chip.
Keywords: other

first: Paul

last: Russell


title: Effect of formula feeding and hypoxia on Necrotizing Enterocolitis (NEC) development

summary:
Necrotizing Enterocolitis (NEC) is an inflammation causing injury to the bowel in newborns. This project uses a rodent model that mimics the intestinal pathological changes seen in NEC to study the effect of formula feeding and hypoxia on NEC development
Keywords: time series, diet, hypoxia

first: Jeffrey

last: Upperman


title: Acute Quadriplegic Myopathy

status: Public on Feb 06 2004

summary:
AQM shows acute muscle wasting and weakness. Key aspects of AQM include muscle atrophy and myofilament loss. Gene expression profiling, using muscle biopsies from AQM, neurogenic atrophy and normal controls, showed that both myogenic and neurogenic atrophy share induction of myofiber-specific ubiquitin/proteosome pathways while only the AQM shows a specific strong induction of transforming growth factor (TGF)-beta/MAPK pathways.
Keywords: other


title: PGA Rat Liver Methylprednisolone

summary:
Summary: The liver is the major site of gluconeogenesis, fat processing and distribution, as well as drug and xenobiotic metabolism. Altered gene expression in the liver is centrally invovled in both the immuosuppressive and the energetic actions of corticosteroids.

Hypothesis: That pharmacodynamics can be derived from expression profiling data.

Specific Aim: The aim of this project is to identify distinct temporal patters of RNA expression in the liver of rats following a bolus dose of the corticosteroid methylprednisolone. 47 RG_U34A chips were used for 17 time points.

first: Richard

last: Almon


title: Lung ventilation

summary:
This project focuses both on the separate and combined effects of large tidal volume ventilation and hyperoxia on gene expression in the lungs of anesthetized rats.  Rats were either mechanically or spontaneously ventilated at either 21 or 100% oxygen and expression levels were evaluated on RG_U34 GeneChips.
Keywords: other

first: Skip

last: Pearse


title: Pharmacogenomic effect of corticosteroid in skeletal muscle

first: Eric

last: Hoffman

summary:
The aim of this project is to identify distinct temporal patterns of RNA expression in the skeletal muscle of rats following a bolus dose of the corticosteroid methylprednisolone.  51 RG_U34A chips were used over 17 time points.
Keywords: other


title: Sex differences in immune response

summary:
In the field, adult male rodents are more frequently infected with hantaviruses than females.  Early data suggests that sex steroid hormones modulate sex differences in host immune response.  This project focuses on elucidating sex differences in gene expression in the lungs of infected males 15 and 40 days post infection with Seoul virus (naturally occurring hantavirus in Norway rats) relative to infected females 15 and 40 days post infection on 12 RG_U34 GeneChips.
Keywords: other

first: Greg

last: Glass


title: Vascular remodeling following pulmonary hypertension

summary:
Hypoxia can induce vasoconstriction followed by vascular remodeling including hypertrophy and hyperplasia of pulmonary vascular smooth muscle and proliferation of endothelial cells.  The goal of this project is to elucidate the genes involved in vascular remodeling following pulmonary hypertension.  Total RNA was isolated from lungs of normoxic  and hypoxic treated animals.
Keywords: other

first: Dechun

last: Li


title: Sleep apnea and glucose metabolism

summary:
This study examines the relationship between sleep apnea and glucose metabolism.  Physiological studies have demonstrated that 5 days of exposure to intermittent hypoxia (similar to what occurs with sleep apnea) leads to significant improvements in glucose tolerance. Therefore, this study investigates the hypothesis that intermittent hypoxia may lead to upregulation of some novel peptide(s) that have a powerful glucose lowering action.
Keywords: other

first: Christopher

last: O'Donnell


title: Allergen-induced goblet cells

summary:
High numbers of goblet cells in airways contribute to the mucus obstruction characteristic of asthmatic airways.  Allergen challenged mice exhibit robust expression of goblet cells within airway surface epithelium.  This study looks at the temporal analysis of IL-13 exposed murine airways to elucidate pathways that result in differentiation of airway epithelial cells to goblet cells.
Keywords: other

first: Mary

last: Rose


title: Non-union skeletal fractures

summary:
Non-union skeletal fractures are characterized by their inability to heal six months after injury.  Left untreated, the non-union fracture may cause advanced arthritis or loss of function in the affected limb.  Arrays were used to identify the mechanisms that lead to lack of skeletal repair in non-unions.  These profiles are the non-union callous samples pooled from five individuals
Keywords: other

first: Dietrich

last: Stephan


title: STRRIDE Study

status: Public on Apr 08 2004

summary:
STRRIDE is an exercise intervention study of different doses and intensities in overweight women and men with the metabolic syndrome. We profiled biopsies from 3 female and 3 male STRRIDE subjects in the “high” exercise group (2,200 kCal/wk). Muscle biopsies were profiled at entry (0h), and after 9 months of aerobic training (24 hrs post-last bout, 96 hrs post last bout, and 336h (14 days) de-training). Included also are pilot expression data from 3 male subjects.
Keywords: other

first: William

last: Kraus


title: Alveolar septation

summary:
The Mg-delta strain of fibrillin-1 deficient mice display an early defect in alveolar septation.  This study attempts to identify expression patterns in the mutant mouse lung compared to their wild-type littermates that suggest pathways that are critical for normal septation.  This experiment focuses on postnatal days 1 and 5.  Other time points will be added at a later date.
Keywords: other

first: Enid

last: Neptune


title: Allergic response to ragweed in lung

summary:
An important feature of human asthma and animal models of asthma is airway hyperresponsiveness. The symptoms of asthma are a narrowing of the airways caused by edema and the influx of inflammatory cells. The aim of this project is to determine the temporal relationship between gene expression and airway allergen challenge. 4 weeks old BALB/CJ mice were challenged on days 0,3,10 and 17 with PBS and ragweed pollen protein plus Alum.
Keywords: time series, allergen

first: Marsha

last: Wills-Karp


title: Alveoli septation inhibition and protection

summary:
It has been shown that dexamethasone (Dex) impairs the normal lung septation that occurs in the early postnatal period. Treatment with retinoic acid (ATRA) abrogates the effects of Dex. To understand the molecular basis for the Dex indiced inhibition of the formation of the alveoli and the ability of ATRA to prevent the inhibition of septation, gene expression was analyzed in 4-day old mice treated with diluent (control), Dex-treated and ATRA+Dex-treated.
Keywords: other

first: Linda

last: Clerch


title: Chronic obstructive pulmonary disease

summary:
Diaphragm muscles in Chronic Obstructive Pulmonary Disease (COPD) patients undergo an adaptive fast to slow transformation that includes cellular adaptations. This project studies the signaling mechanisms responsible for this transformation.
Keywords: other

first: N

middle: A

last: Rubinstein


title: Ozone effect on airways hyperpermability

summary:
Ozone is a very common environmental pollutant and has been associated with the exacerbation of cardiopulmonary diseases like asthma. In this study the molecular mechanisms underlying the effect of ozone on airways hyperpermability were investigated. Two strains of mice, HeJ (Tlr4 mutant) and OuJ (wildtype) were exposed continuously to air or 0.3ppm of ozone. Lungs were removed and RNA was collected to generate expression profiles.
Keywords: other


title: Alveoli loss during caloric restriction time course

summary:
Pulmonary alveoli are complex architectural units thought to undergo endogenous or pharmacologically induced programs of regeneration and degeneration. To study the molecular mechanism of alveoli loss mice were calorie restricted at different timepoints. Lungs were harvested and processed for RNA extraction.
Keywords: other

first: Gloria

middle: D

last: Massaro

first: Donald


title: Obesity and fatty acid oxidation

summary:
It has been found that fat oxidation is reduced in the skeletal muscle of obese humans.  This study aims to identify the mRNA of proteins involved in fat oxidation that may be reduced in obese and morbidly obese individuals.  Information gathered will help in understanding how obesity contributes to cardiovascular disease via insulin resistance.
Keywords: other

first: J

last: Houmard


title: Congestive heart failure in dog

summary:
Canine tachycardia-induced cardiomyopathy caused by several weeks of rapid ventricular pacing is a well-established animal model of congestive heart failure.  However, little is known about the underlying changes in gene expression that occur in the canine myocardium after the induction of heart failure.  This project aims to compare expression profiles in left ventricular free wall samples from control dogs and dogs with pacing-induced heart failure on the custom MuscleChip.
Keywords: other

first: T

last: Cappola

last: Hare


title: Alternatively activated macrophages

summary:
Similar to asthma, nematode infections are commonly associated with production of Th2 cytokines and hyporesponsive T cells.  This T cell phenotype has been reported to be induced by IL-4 dependent macrophages termed alternatively activated macrophages (AAM).  Additionally, AAM have been implicated in several pulmonary diseases, including allergic asthma.  This study examines the potential importance of AAM as immune regulatory cells in both infectious and noninfectious disease contexts. http://www.hopkins-genomics.org/asthma/asthma006/index.html
Keywords: other

first: Alan

last: Scott


title: Expression profiling of extraocular muscles

summary:
The extraocular muscles (EOM) are anatomically and physiologically distinct from other skeletal muscles. EOM are preferentially affected in mitochondrial myopathies, but spared in Duchenne's muscular dystrophy. The anatomical and pathophysiological properties of EOM have been attributed to their unique molecular makeup: an allotype. We used expression profiling to define molecular features of the EOM allotype. We found 346 differentially expressed genes in rat EOM compared with tibialis anterior, based on a twofold difference cutoff. Genes required for efficient, fatigue-resistant, oxidative metabolism were increased in EOM, whereas genes for glycogen metabolism were decreased. EOM also showed increased expression of genes related to structural components of EOM such as vessels, nerves, mitochondria, and neuromuscular junctions. Additionally, genes related to specialized functional roles of EOM such as the embryonic and EOM-specific myosin heavy chains and genes for muscle growth, development, and/or regeneration were increased. The EOM expression profile was validated using biochemical, structural, and molecular methods. Characterization of the EOM expression profile begins to define gene transcription patterns associated with the unique anatomical, metabolic, and pathophysiological properties of EOM.
Keywords: other

first: M

last: Fischer

last: Gorospe

first: E

last: Felder

first: S

last: Bogdanovich

first: F

last: Pedrosa-Domellof

first: R

last: Ahima

last: Khurana


title: Expression profiling of medulloblastoma

first: Eric

last: Hoffman

summary:
Little is known about the genetic regulation of medulloblastoma dissemination, but metastatic medulloblastoma is highly associated with poor outcome. We obtained expression profiles of 23 primary medulloblastomas clinically designated as either metastatic (M+) or non-metastatic (M0) and identified 85 genes whose expression differed significantly between classes. Using a class prediction algorithm based on these genes and a leave-one-out approach, we assigned sample class to these tumors (M+ or M0) with 72% accuracy and to four additional independent tumors with 100% accuracy. We also assigned the metastatic medulloblastoma cell line Daoy to the metastatic class. Notably, platelet-derived growth factor receptor alpha (PDGFRA) and members of the downstream RAS/mitogen-activated protein kinase (MAPK) signal transduction pathway are upregulated in M+ tumors. Immunohistochemical validation on an independent set of tumors shows significant overexpression of PDGFRA in M+ tumors compared to M0 tumors. Using in vitro assays, we show that platelet-derived growth factor alpha (PDGFA) enhances medulloblastoma migration and increases downstream MAP2K1 (MEK1), MAP2K2 (MEK2), MAPK1 (p42 MAPK) and MAPK3 (p44 MAPK) phosphorylation in a dose-dependent manner. Neutralizing antibodies to PDGFRA blocks MAP2K1, MAP2K2 and MAPK1/3 phosphorylation, whereas U0126, a highly specific inhibitor of MAP2K1 and MAP2K2, also blocks MAPK1/3. Both inhibit migration and prevent PDGFA-stimulated migration. These results provide the first insight into the genetic regulation of medulloblastoma metastasis and are the first to suggest a role for PDGFRA and the RAS/MAPK signaling pathway in medulloblastoma metastasis. Inhibitors of PDGFRA and RAS proteins should therefore be considered for investigation as possible novel therapeutic strategies against medulloblastoma.
Keywords: other

last: MacDonald

first: K

last: Brown

first: B

last: LaFleur

last: Peterson

first: C

last: Lawlor

first: Y

last: Chen

last: Packer

first: P

last: Cogen

first: D

last: Stephan


title: Genetic basis of sensitivity to pulmonary fibrosis

summary:
The murine pulmonary response is strain specific.  Susceptible strains such as C57BL6/J experience an inflammatory response followed by progressive lung disease.  Resistant strains such as Balb/c do not experience significant degrees of inflammation or fibrosis.  This study aims to determine the genetic basis of sensitivity differences between strains
Keywords: other

middle: W

first: David

last: Moller


title: Response of rat muscle to acute resistance exercise

summary:
To further understand molecular mechanisms underlying skeletal muscle hypertrophy, expression profiles of translationally and transcriptionally regulated genes were characterized following an acute bout of maximally activated eccentric contractions. Experiments demonstrated that translational mechanisms contribute to acute gene expression changes following high resistance contractions with two candidate mRNAs, basic fibroblast growth factor (bFGF) and elongation factor-1 alpha (EF1alpha), targeted to the heavier polysomal fractions after a bout of contractions. Gene profiling was performed using Affymetrix Rat U34A GeneChips with either total RNA or polysomal RNA at one and six hours following contractions. There were 18 genes that changed expression at one hour and 70 genes that were different (60 genes increased:10 genes decreased)at six hours after contractions. The model from this profiling suggests that following high resistance contractions skeletal muscle shares a common growth profile with proliferating cells exposed to serum. This cluster of genes can be classified as "growth" genes and is commonly associated with progression of the cell cycle. However, a unique aspect was that there was induction of a cluster of tumour suppressor or antigrowth genes. We propose that this cluster of "antigrowth" genes is induced by the stress of contractile activity and may act to maintain skeletal muscle in the differentiated state. From the profiling results, further experiments determined that p53 levels increased in skeletal muscle at 6 h following contractions. This novel finding of p53 induction following exercise also demonstrates the power of expression profiling for identification of novel pathways involved in the response to muscle contraction.
Keywords: other

first: G

last: Nader

last: Baar

last: Fedele

last: Esser


title: Expression profiling in the muscular dystrophies

summary:
This is a large series human Duchenne muscular dystrophy patient muscle biopsies, in specific age groups, using all available Affymetrix arrays (including a custom MuscleChip produced by the Hoffman lab). Both mixed groups of patients (5 patient biopsies per group) and individual biopsies were done.

Hypothesis: That the progression of DMD can be understood in terms of muscle molecular remodeling.
Keywords: other

last: Zhao

last: Borup


title: PGA Human CD4+ Lymphocytes

last: Hoffman

summary:
This project is based on the hygiene hypothesis that exposure to TB provides a protective mechanism against asthma through specific cytokines and the balance of Th1, Th2 cells.  Additionally, expression changes are examined in patients with and without atopy in combination with asthma and PPD status.  Expression levels were evaluated in CD4+ cells isolated from peripheral blood of 30 patients.  Each patient was evaluated on the entire U133 Affymetrix GeneChip set.
Hypothesis: That CD4+ cells have specific diagnostic profiles based upon atopy and asthma state. Further information at http://www.hopkins-genomics.org/asthma/asthma001/index.html
Specific Aim: To define diagnostic genes from purified CD4+ blood cells have specific diagnostic profiles based upon atopy and asthma state. Further information at http://www.hopkins-genomics.org/asthma/asthma001/index.html
Keywords: other

last: Diette


title: Asthma exacerbatory factors

summary:
The exacerbation of disease in asthmatics has been linked to both exposure to environmental agents as well as to the presence of virus in airways, particularly rhinovirus.  The hypothesis tested in these experiments is that differences in gene expression profiles in epithelial cells derived from asthmatic and normal airways can be linked to enhanced responsiveness of the epithelium in its pro-inflammatory, immulogic or other activities that may lead to the exacerbation of disease.
Keywords: other

first: W

last: Spannhake


title: mRNA expression in regenerated mdx mouse skeletal muscle

summary:
Despite over 3,000 articles published on dystrophin in the last 15 years, the reasons underlying the progression of the human disease, differential muscle involvement, and disparate phenotypes in different species are not understood. The present experiment employed a screen of 12,488 mRNAs in 16-wk-old mouse mdx muscle at a time when the skeletal muscle is avoiding severe dystrophic pathophysiology, despite the absence of a functional dystrophin protein. A number of transcripts whose levels differed between the mdx and human Duchenne muscular dystrophy were noted. A fourfold decrease in myostatin mRNA in the mdx muscle was noted. Differential upregulation of actin-related protein 2/3 (subunit 4), beta-thymosin, calponin, mast cell chymase, and guanidinoacetate methyltransferase mRNA in the more benign mdx was also observed. Transcripts for oxidative and glycolytic enzymes in mdx muscle were not downregulated. These discrepancies could provide candidates for salvage pathways that maintain skeletal muscle integrity in the absence of a functional dystrophin protein in mdx skeletal muscle.
Keywords: other

last: Tseng

first: J

last: Pattison

last: Gordon

last: Granchelli

last: Madsen

first: L

middle: C

last: Folk

last: Booth


title: Temporal profiling in muscle regeneration.

summary:
Temporal expression profiling was utilized to define transcriptional regulatory pathways in vivo in a mouse muscle regeneration model. Potential downstream targets of MyoD were identified by temporal expression, promoter data base mining, and gel shift assays; Slug and calpain 6 were identified as novel MyoD targets. Slug, a member of the snail/slug family of zinc finger transcriptional repressors critical for mesoderm/ectoderm development, was further shown to be a downstream target by using promoter/reporter constructs and demonstration of defective muscle regeneration in Slug null mice.
Keywords: other

last: Iezzi

last: Carver

last: Dressman

first: T

last: Gridley

first: V

last: Sartorelli


title: CNS Regeneration

summary:
Summary:  	Spinal cord injury (SCI) is a damage to the spinal cord induced by trauma or desease resulting in a loss of mobility or feeling. SCI is characterized by a primary mechanical injury followed by a secondary injury in which several molecular events are altered in the spinal cord often resulting in loss of neuronal function.

Hypothesis: 	Spinal cord injury (SCI) induces a cascade of molecular events including the activation of genes associated with transcription factors, inflammation, oxidative stress, ionic imbalance, apoptosis and neuroregeneration which suggests the existance of endogenous reparative attempts. However, not all mechanisms following SCI are well known.

Specific Aim: 	The goal of this project is to analyze the molecular events following spinal cord injury 1 cm above, below, and at the site of injury (T9), aiming at finding potential new targets to improve recovery and therapy.
Keywords: other

first: S

last: Di Giovanni

last: Knoblach

last: Brandoli

last: Aden

first: E

first: A

middle: I

last: Faden