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Search Results: 1 - 10 of 418522 matches for " Kim M. Lonergan "
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Effect of active smoking on the human bronchial epithelium transcriptome
Raj Chari, Kim M Lonergan, Raymond T Ng, Calum MacAulay, Wan L Lam, Stephen Lam
BMC Genomics , 2007, DOI: 10.1186/1471-2164-8-297
Abstract: Twenty-four SAGE profiles of the bronchial epithelium of eight current, twelve former and four never smokers were generated and analyzed. In total, 3,111,471 SAGE tags representing over 110 thousand potentially unique transcripts were generated, comprising the largest human SAGE study to date. We identified 1,733 constitutively expressed genes in current, former and never smoker transcriptomes. We have also identified both reversible and irreversible gene expression changes upon cessation of smoking; reversible changes were frequently associated with either xenobiotic metabolism, nucleotide metabolism or mucus secretion. Increased expression of TFF3, CABYR, and ENTPD8 were found to be reversible upon smoking cessation. Expression of GSK3B, which regulates COX2 expression, was irreversibly decreased. MUC5AC expression was only partially reversed. Validation of select genes was performed using quantitative RT-PCR on a secondary cohort of nine current smokers, seven former smokers and six never smokers.Expression levels of some of the genes related to tobacco smoking return to levels similar to never smokers upon cessation of smoking, while expression of others appears to be permanently altered despite prolonged smoking cessation. These irreversible changes may account for the persistent lung cancer risk despite smoking cessation.Lung cancer has the highest mortality rate among all types of malignancies, accounting for approximately 29% of all cancer-related deaths in the United States [1]. It has been estimated that in 2006 alone, the number of new lung cancer cases will exceed 174,000 and approximately 163,000 people will die of this disease [1]. Tobacco smoking accounts for 85% of the lung cancers. Former heavy smokers remain at an elevated risk for developing lung cancer even years after they stop smoking [2,3]. Fifty percent of newly diagnosed lung cancer patients are former smokers [4]. It is therefore important to understand the effects of tobacco smoking on the
Transcriptome Profiles of Carcinoma-in-Situ and Invasive Non-Small Cell Lung Cancer as Revealed by SAGE
Kim M. Lonergan,Raj Chari,Bradley P. Coe,Ian M. Wilson,Ming-Sound Tsao,Raymond T. Ng,Calum MacAulay,Stephen Lam,Wan L. Lam
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0009162
Abstract: Non-small cell lung cancer (NSCLC) presents as a progressive disease spanning precancerous, preinvasive, locally invasive, and metastatic lesions. Identification of biological pathways reflective of these progressive stages, and aberrantly expressed genes associated with these pathways, would conceivably enhance therapeutic approaches to this devastating disease.
Comprehensive serial analysis of gene expression of the cervical transcriptome
Ashleen Shadeo, Raj Chari, Greg Vatcher, Jennifer Campbell, Kim M Lonergan, Jasenka Matisic, Dirk van Niekerk, Thomas Ehlen, Dianne Miller, Michele Follen, Wan L Lam, Calum MacAulay
BMC Genomics , 2007, DOI: 10.1186/1471-2164-8-142
Abstract: We have sequenced 691,390 tags from four L-SAGE libraries increasing the existing gene expression data on cervical tissue by 20 fold. One-hundred and eighteen unique tags were highly expressed in normal cervical tissue and 107 of them mapped to unique genes, most belong to the ribosomal, calcium-binding and keratinizing gene families. We assessed these genes for aberrant expression in CIN III and five genes showed altered expression. In addition, we have identified twelve unique HPV 16 SAGE tags in the CIN III libraries absent in the normal libraries.Establishing a baseline of gene expression in normal cervical tissue is key for identifying changes in cancer. We demonstrate the utility of this baseline data by identifying genes with aberrant expression in CIN III when compared to normal tissue.Approximately 500,000 women are diagnosed with cervical cancer worldwide each year and more than half of them will die from this disease [1]. The highest incidence rates are observed in developing countries where it is the second most prevalent cancer in women and remains a leading cause of cancer related death [1]. Widely implemented screening programs have been responsible for the much lower incidence and mortality rates seen in the developed world. Present day screening methods primarily identify precancer lesions termed cervical intraepithelial neoplasia (CIN). CIN lesions are classified into three subgroups, CIN I, CIN II and CIN III, corresponding to mild, moderate and severe dysplasia/carcinoma in situ (CIS), respectively. CIN III lesions have a high likelihood of progression to invasive disease if left untreated [2]. Human Papillomavirus (HPV) has long been established as a necessary but not sufficient cause for cervical carcinoma development. HPV is detected in 99% of invasive disease, 94% of CIN lesions and 46% of normal cervical epithelium [2]. The high risk strains HPV 16 and HPV 18 are most prevalent in invasive disease.A comprehensive characterization of gene exp
Human Cancer Long Non-Coding RNA Transcriptomes
Ewan A. Gibb, Emily A. Vucic, Katey S. S. Enfield, Greg L. Stewart, Kim M. Lonergan, Jennifer Y. Kennett, Daiana D. Becker-Santos, Calum E. MacAulay, Stephen Lam, Carolyn J. Brown, Wan L. Lam
PLOS ONE , 2011, DOI: 10.1371/journal.pone.0025915
Abstract: Once thought to be a part of the ‘dark matter’ of the genome, long non-coding RNAs (lncRNAs) are emerging as an integral functional component of the mammalian transcriptome. LncRNAs are a novel class of mRNA-like transcripts which, despite no known protein-coding potential, demonstrate a wide range of structural and functional roles in cellular biology. However, the magnitude of the contribution of lncRNA expression to normal human tissues and cancers has not been investigated in a comprehensive manner. In this study, we compiled 272 human serial analysis of gene expression (SAGE) libraries to delineate lncRNA transcription patterns across a broad spectrum of normal human tissues and cancers. Using a novel lncRNA discovery pipeline we parsed over 24 million SAGE tags and report lncRNA expression profiles across a panel of 26 different normal human tissues and 19 human cancers. Our findings show extensive, tissue-specific lncRNA expression in normal tissues and highly aberrant lncRNA expression in human cancers. Here, we present a first generation atlas for lncRNA profiling in cancer.
Up regulation in gene expression of chromatin remodelling factors in cervical intraepithelial neoplasia
Ashleen Shadeo, Raj Chari, Kim M Lonergan, Andrea Pusic, Dianne Miller, Tom Ehlen, Dirk Van Niekerk, Jasenka Matisic, Rebecca Richards-Kortum, Michele Follen, Martial Guillaud, Wan L Lam, Calum MacAulay
BMC Genomics , 2008, DOI: 10.1186/1471-2164-9-64
Abstract: In this study, we have identified gene expression changes across 16 cervical cases (CIN I, CIN II, CIN III and normal cervical epithelium) using the unbiased long serial analysis of gene expression (L-SAGE) method. The 16 L-SAGE libraries were sequenced to the level of 2,481,387 tags, creating the largest SAGE data collection for cervical tissue worldwide. We have identified 222 genes differentially expressed between normal cervical tissue and CIN III. Many of these genes influence biological functions characteristic of cancer, such as cell death, cell growth/proliferation and cellular movement. Evaluation of these genes through network interactions identified multiple candidates that influence regulation of cellular transcription through chromatin remodelling (SMARCC1, NCOR1, MRFAP1 and MORF4L2). Further, these expression events are focused at the critical junction in disease development of moderate dysplasia (CIN II) indicating a role for chromatin remodelling as part of cervical cancer development.We have created a valuable publically available resource for the study of gene expression in precancerous cervical lesions. Our results indicate deregulation of the chromatin remodelling complex components and its influencing factors occur in the development of CIN lesions. The increase in SWI/SNF stabilizing molecule SMARCC1 and other novel genes has not been previously illustrated as events in the early stages of dysplasia development and thus not only provides novel candidate markers for screening but a biological function for targeting treatment.Cervical cancer affects approximately 500,000 women worldwide each year with highest rates in developing countries [1]. Cervical intraepithelial neoplasia (CIN) is a precursor lesion to cervical cancer and can be further subdivided into CIN I, CIN II and CIN III (mild, moderate and severe dysplasia, respectively). Most CIN I lesions spontaneously regress to normal however CIN III lesions are much more likely to progress to c
A sequence-based approach to identify reference genes for gene expression analysis
Raj Chari, Kim M Lonergan, Larissa A Pikor, Bradley P Coe, Chang Zhu, Timothy HW Chan, Calum E MacAulay, Ming-Sound Tsao, Stephen Lam, Raymond T Ng, Wan L Lam
BMC Medical Genomics , 2010, DOI: 10.1186/1755-8794-3-32
Abstract: Serial analysis of gene expression (SAGE) profiles of non-malignant and malignant lung samples were compared using a permutation test to identify the most stably expressed genes across all samples. Subsequently, the specificity of the reference genes was evaluated across multiple tissue types, their constancy of expression was assessed using quantitative RT-PCR (qPCR), and their impact on differential expression analysis of microarray data was evaluated.We show that (i) conventional references genes such as ACTB and GAPDH are highly variable between cancerous and non-cancerous samples, (ii) reference genes identified for lung cancer do not perform well for other cancer types (breast and brain), (iii) reference genes identified through SAGE show low variability using qPCR in a different cohort of samples, and (iv) normalization of a lung cancer gene expression microarray dataset with or without our reference genes, yields different results for differential gene expression and subsequent analyses. Specifically, key established pathways in lung cancer exhibit higher statistical significance using a dataset normalized with our reference genes relative to normalization without using our reference genes.Our analyses found NDUFA1, RPL19, RAB5C, and RPS18 to occupy the top ranking positions among 15 suitable reference genes optimal for normalization of lung tissue expression data. Significantly, the approach used in this study can be applied to data generated using new generation sequencing platforms for the identification of reference genes optimal within diverse contexts.Gene expression profiling, including quantitative RT-PCR (qPCR) and microarray experimentation, is invaluable for the molecular analysis of biological systems. The interpretation of results from such experiments (i.e., the determination of differential expression for a particular gene among datasets) is strongly influenced by the selection of reference genes for normalization across datasets [1]. Specific
From mass media to new media in contemporary Irish drama: Billy Roche's On Such As We and Paul Meade's Skin Deep
Patrick Lonergan
Ilha do Desterro , 2010,
Abstract: This article explores the impact of new media and the mass media on the production, composition and reception of contemporary Irish drama. It considers the emergence of several tensions in that genre, notably that between mobility and stasis and the local and the global. This development is considered in relation to a discussion of two plays: Billy Roche's On Such As We, which was produced at the Peacock Theatre in 2001, and Paul Meade's Skin Deep, premiered by his company Gúna Nua at the Project Arts Centre in Dublin in 2003.
Time-Dependent Expression of Arc and Zif268 after Acquisition of Fear Conditioning
Mary E. Lonergan,Georgette M. Gafford,Timothy J. Jarome,Fred J. Helmstetter
Neural Plasticity , 2010, DOI: 10.1155/2010/139891
Abstract: Memory consolidation requires transcription and translation of new protein. Arc, an effector immediate early gene, and zif268, a regulatory transcription factor, have been implicated in synaptic plasticity underlying learning and memory. This study explored the temporal expression profiles of these proteins in the rat hippocampus following fear conditioning. We observed a time-dependent increase of Arc protein in the dorsal hippocampus 30-to-90-minute post training, returning to basal levels at 4 h. Zif268 protein levels, however, gradually increased at 30-minute post training before peaking in expression at 60 minute. The timing of hippocampal Arc and zif268 expression coincides with the critical period for protein synthesis-dependent memory consolidation following fear conditioning. However, the expression of Arc protein appears to be driven by context exploration, whereas, zif268 expression may be more specifically related to associative learning. These findings suggest that altered Arc and zif268 expression are related to neural plasticity during the formation of fear memory. 1. Introduction A predominant question in neuroscience is how memory functions are supported by the central nervous system and what cellular processes are necessary. One focus of this research is on protein-dependent synaptic modifications that occur as a consequence of neuronal activity. Signaling cascades activated at the time of learning can induce the transcription of particular genes, ultimately leading to de novo protein synthesis and subsequent structural changes to support long-term memories. Gene expression plays a critical role in these postactivation changes in neurons. Immediate-early genes (IEGs) are induced soon after neuronal activity, and they participate in diverse functions. Some IEGs are regulatory transcription factors (e.g., zif268/Egr1) responsible for inducing transcription of late-response genes, while others are effector IEGs (e.g., Arc/Arg3.1) that are directly involved in cellular changes at locations such as the cytoskeleton or receptors. Many IEGs are translated in the soma. However, the transcripts of some IEGs, such as activity-regulated cytoskeleton-associated protein (Arc), are transported to the dendrites and protein synthesis occurs there [1], thus making Arc a reasonable target for researchers investigating the underlying mechanisms of postsynaptic changes supporting memory formation. Arc (also called Arg3.1) is a plasticity-related gene whose induction occurs soon after synaptic activation [2–4], mRNA transcription is independent of de novo
Tax Reform: The Cure to the United States’ Economic Slowdown
Thomas Joseph Lonergan
Pitt Political Review , 2011, DOI: 10.5195/ppr.2011.7
Abstract: Benjamin Franklin once said, “The only two certainties in life are death and taxes.” This infamous saying is as true today as it was more than 200 years ago when it was coined; the only difference between taxes today and taxes in the days of Ben Franklin is the complexity of how taxes are managed. As the American economy teeters on the brink of its second recession in four years, tax reform may be the solution to the economic situation the United States finds itself in today.
Key to the 2012 Presidential Election: The Philadelphia Suburbs
Thomas Joseph Lonergan
Pitt Political Review , 2012, DOI: 10.5195/ppr.2012.25
Abstract: Mitt Romney or Barack Obama: this is the choice Pennsylvanian voters will have in November as the 2012 presidential election draws closer. The voters of Pennsylvania will be at the height of importance in the history of American presidential elections, playing a key role as one of the leading battleground states in this upcoming election. With twenty electoral votes, tied for the fifth most of any state in the country, both campaigns will look to focus a great amount of time and money on trying to win this crucial state. And at the center of this fierce battle between the current GOP presumptive nominee and the President of the United States are four counties that comprise the suburbs of Philadelphia. These counties will ultimately decide the fate of Pennsylvania’s electoral votes, and possibly even the election itself.
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