Browsing by Author "Bavarva, Jasmin H."
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- Characterizing the Genetic Basis for Nicotine Induced Cancer Development: A Transcriptome Sequencing StudyBavarva, Jasmin H.; Tae, Hongseok; Settlage, Robert E.; Garner, Harold R. (PLOS, 2013-06-18)Nicotine is a known risk factor for cancer development and has been shown to alter gene expression in cells and tissue upon exposure. We used Illumina® Next Generation Sequencing (NGS) technology to gain unbiased biological insight into the transcriptome of normal epithelial cells (MCF-10A) to nicotine exposure. We generated expression data from 54,699 transcripts using triplicates of control and nicotine stressed cells. As a result, we identified 138 differentially expressed transcripts, including 39 uncharacterized genes. Additionally, 173 transcripts that are primarily associated with DNA replication, recombination, and repair showed evidence for alternative splicing. We discovered the greatest nicotine stress response by HPCAL4 (up-regulated by 4.71 fold) and NPAS3 (down-regulated by -2.73 fold); both are genes that have not been previously implicated in nicotine exposure but are linked to cancer. We also discovered significant down-regulation (-2.3 fold) and alternative splicing of NEAT1 (lncRNA) that may have an important, yet undiscovered regulatory role. Gene ontology analysis revealed nicotine exposure influenced genes involved in cellular and metabolic processes. This study reveals previously unknown consequences of nicotine stress on the transcriptome of normal breast epithelial cells and provides insight into the underlying biological influence of nicotine on normal cells, marking the foundation for future studies.
- 'Cut from the same cloth': Shared microsatellite variants among cancers link to ectodermal tissues-neural tube and crest cellsKarunasena, Enusha; McIver, Lauren J.; Bavarva, Jasmin H.; Wu, Xiaowei; Zhu, Hongxiao; Garner, Harold R. (Impact Journals, 2015-09-08)
- Gene Expression Profiling of Human Vaginal Cells In Vitro Discriminates Compounds with Pro-Inflammatory and Mucosa-Altering Properties: Novel Biomarkers for Preclinical Testing of HIV Microbicide CandidatesZalenskaya, Irina A.; Joseph, Theresa; Bavarva, Jasmin H.; Yousefieh, Nazita; Jackson, Suzanne S.; Fashemi, Titilayo; Yamamoto, Hidemi S.; Settlage, Robert E.; Fichorova, Raina N.; Doncel, Gustavo F. (PLOS, 2015-06-08)Background Inflammation and immune activation of the cervicovaginal mucosa are considered factors that increase susceptibility to HIV infection. Therefore, it is essential to screen candidate anti-HIV microbicides for potential mucosal immunomodulatory/inflammatory effects prior to further clinical development. The goal of this study was to develop an in vitro method for preclinical evaluation of the inflammatory potential of new candidate microbicides using a microarray gene expression profiling strategy. Methods To this end, we compared transcriptomes of human vaginal cells (Vk2/E6E7) treated with well-characterized pro-inflammatory (PIC) and non-inflammatory (NIC) compounds. PICs included compounds with different mechanisms of action. Gene expression was analyzed using Affymetrix U133 Plus 2 arrays. Data processing was performed using GeneSpring 11.5 (Agilent Technologies, Santa Clara, CA). Results Microarraray comparative analysis allowed us to generate a panel of 20 genes that were consistently deregulated by PICs compared to NICs, thus distinguishing between these two groups. Functional analysis mapped 14 of these genes to immune and inflammatory responses. This was confirmed by the fact that PICs induced NFkB pathway activation in Vk2 cells. By testing microbicide candidates previously characterized in clinical trials we demonstrated that the selected PIC-associated genes properly identified compounds with mucosa-altering effects. The discriminatory power of these genes was further demonstrated after culturing vaginal cells with vaginal bacteria. Prevotella bivia, prevalent bacteria in the disturbed microbiota of bacterial vaginosis, induced strong upregulation of seven selected PIC-associated genes, while a commensal Lactobacillus gasseri associated to vaginal health did not cause any changes. Conclusions In vitro evaluation of the immunoinflammatory potential of microbicides using the PIC-associated genes defined in this study could help in the initial screening of candidates prior to entering clinical trials. Additional characterization of these genes can provide further insight into the cervicovaginal immunoinflammatory and mucosal-altering processes that facilitate or limit HIV transmission with implications for the design of prevention strategies.
- Somatic intronic microsatellite loci differentiate glioblastoma from lower-grade gliomasKarunasena, Enusha; McIver, Lauren J.; Rood, Brian R.; Wu, Xiaowei; Zhu, Hongxiao; Bavarva, Jasmin H.; Garner, Harold R. (Impact Journals, 2014-08-15)
- Updating microbial genomic sequences: improving accuracy & innovationTae, Hongseok; Karunasena, Enusha; Bavarva, Jasmin H.; Garner, Harold R. (2014-11-07)Background Many bacterial genome sequences completed using the Sanger method may contain assembly errors due in-part to low sequence coverage driven by cost. Findings To illustrate the need for re-sequencing of pre-nextgen genomes and to validate sequenced genomes, we conducted a series of experiments, using high coverage sequencing data generated by a Illumina Miseq sequencer to sequence genomic DNAs of Bacteroides fragilis NCTC 9343, Salmonella enterica subsp. enterica serovar Paratyphi A str. ATCC 9150, Vibrio cholerae O1 biovar El Tor str. N16961, Bacillus halodurans C-125 and Caulobacter crescentus CB15, which had previously been sequenced by the Sanger method during the early 2000’s. Conclusions This study revealed a number of discrepancies between the published assemblies and sequence read alignments for all five bacterial species, suggesting that the continued use of these error-containing genomes and their genetic information may contribute to false conclusions and/or incorrect future discoveries when they are used.