Biomedical subjects

Nigam Shah

Publications and source records attributed to Nigam Shah.

4 recordsLinked to original sources

PubMed2005

Temporal evolution of the Arabidopsis oxidative stress response.

We have carried out a detailed analysis of the changes in gene expression levels in Arabidopsis thaliana ecotype Columbia (Col-0) plants during and for 6 h after exposure to ozone (O3) at 350 parts per billion (ppb) for 6 h. This O3 exposure is sufficient to induce a marked transcriptional response and an oxidative burst, but not to cause substantial tissue damage in Col-0 wild-type plants and is within the range encountered in some major metropolitan areas. We have developed analytical and visualization tools to automate the identification of expression profile groups with common gene ontology (GO) annotations based on the sub-cellular localization and function of the proteins encoded by the genes, as well as to automate promoter analysis for such gene groups. We describe application of these methods to identify stress-induced genes whose transcript abundance is likely to be controlled by common regulatory mechanisms and summarized our findings in a temporal model of the stress response.

Arabidopsis↗

PubMed2003

Characterizing the stress/defense transcriptome of Arabidopsis.

BACKGROUND: To understand the gene networks that underlie plant stress and defense responses, it is necessary to identify and characterize the genes that respond both initially and as the physiological response to the stress or pathogen develops. We used PCR-based suppression subtractive hybridization to identify Arabidopsis genes that are differentially expressed in response to ozone, bacterial and oomycete pathogens and the signaling molecules salicylic acid (SA) and jasmonic acid. RESULTS: We identified a total of 1,058 differentially expressed genes from eight stress cDNA libraries. Digital northern analysis revealed that 55% of the stress-inducible genes are rarely transcribed in unstressed plants and 17% of them were not previously represented in Arabidopsis expressed sequence tag databases. More than two-thirds of the genes in the stress cDNA collection have not been identified in previous studies as stress/defense response genes. Several stress-responsive cis-elements showed a statistically significant over-representation in the promoters of the genes in the stress cDNA collection. These include W- and G-boxes, the SA-inducible element, the abscisic acid response element and the TGA motif. CONCLUSIONS: The stress cDNA collection comprises a broad repertoire of stress-responsive genes encoding proteins that are involved in both the initial and subsequent stages of the physiological response to abiotic stress and pathogens. This set of stress-, pathogen- and hormone-modulated genes is an important resource for understanding the genetic interactions underlying stress signaling and responses and may contribute to the characterization of the stress transcriptome through the construction of standardized specialized arrays.

Arabidopsis↗

PubMed2003

Identification of a global gene expression signature of B-chronic lymphocytic leukemia.

B-chronic lymphocytic leukemia (B-CLL) is an adult-onset leukemia characterized by significant accumulation of apoptosis-resistant monoclonal B lymphocytes. In this study, we performed gene expression profiling on B cells obtained from 10 healthy age-matched individuals and CLL B cells from 38 B-CLL patients to identify key genetic differences between CLL and normal B cells. In addition, we leveraged recent independent studies to assess the reproducibility of our molecular B-CLL signature. We used a novel combination of several methods of data analysis including our own software and identified 70 previously unreported genes that differentiate leukemic cells from normal B cells, as well as confirmed recently reported B-CLL specific expression levels of an additional 10 genes. Importantly, many of these genes have previously been linked with other cancers, thus lending further support to their importance as candidate genes leading to B-CLL pathogenesis. We have also validated a subset of these genes using independent methodologies. Moreover, we show that our genes can be used to create a diagnostics signature that performs with perfect sensitivity and specificity in an independent cohort of 21 B-CLL and 20 normal subjects, thus strongly validating the informative nature of our set of genes. Finally, we identified a group of 31 genes that distinguish between low (Rai stage 0) and high (Rai stage 4) risk patients, suggesting that there may also be a gene expression signature that associates with disease progression.

ATP-Binding Cassette Transporters↗

PubMed2003

Can we identify cellular pathways implicated in cancer using gene expression data?

The cancer state of a cell is characterized by alterations of important cellular processes such as cell proliferation, apoptosis, DNA-damage repair, etc. The expression of genes associated with cancer related pathways, therefore, may exhibit differences between the normal and the cancerous states. We explore various means to find these differences. We analyze 6 different pathways (p53, Ras, Brca, DNA damage repair, NFkappab and beta-catenin) and 4 different types of cancer: colon, pancreas, prostate and kidney. Our results are found to be mostly consistent with existing knowledge of the involvement of these pathways in different cancers. Our analysis constitutes proof of principle that it may be possible to predict the involvement of a particular pathway in cancer or other diseases by using gene expression data. Such method would be particularly useful for the types of diseases where biology is poorly understood.

Biomarkers, Tumor↗