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Tobacco is the primary etiologic agent in worsened lung squamous cell carcinoma (LUSC) outcomes. Meanwhile, it has been shown that etiologic agents alter enhancer RNAs (eRNAs) expression. Therefore, we aimed to identify the effects of tobacco and electronic cigarette (e-cigarette) use on eRNA expression in relation to LUSC outcomes. We extracted eRNA counts from RNA-sequencing data of tumor/adjacent normal tissue and before/after e-cigarette tissue from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO), respectively. Tobacco-mediated LUSC eRNAs were correlated to patient survival, clinical variables, and immune-associated elements. eRNA expression was also correlated to mutation rates through the Repeated Evaluation of Variables Conditional Entropy and Redundance (REVEALER) algorithm and methylated sites through methylationArrayAnalysis. Differential expression analysis was then completed for the e-cigarette data to compare with key tobacco-mediated eRNAs. We identified 684 downregulated eRNAs and 819 upregulated eRNAs associated with tobacco-mediated LUSC, specifically, with the cancer pathological stage. We also observed a decrease in immune cell abundance in tobacco-mediated LUSC. Yet, we found an increased association of eRNA expression with immune cell abundance in tobacco-mediated LUSC. We identified 16 key eRNAs with significant correlations to 8 clinical variables, implicating these eRNAs in LUSC malignancy. Furthermore, we observed that these 16 eRNAs were highly associated with chromosomal alterations and reduced CpG site methylation. Finally, we observed large eRNA expression upregulation with e-cigarette use, which corresponded to the upregulation of the 16 key eRNAs. Our findings provide a novel mechanism by which tobacco and e-cigarette smoke influences eRNA interactions to promote LUSC pathogenesis and provide insight regarding disease progression at a molecular level.
Joseph C. Tsai; Omar A. Saad; Shruti Magesh; Jingyue Xu; Abby C. Lee; Wei Tse Li; Jaideep Chakladar; Mark M. Fuster; Eric Y. Chang; Jessica Wang-Rodriguez; Weg M. Ongkeko. Tobacco Smoke and Electronic Cigarette Vapor Alter Enhancer RNA Expression That Can Regulate the Pathogenesis of Lung Squamous Cell Carcinoma. Cancers 2021, 13, 4225 .
AMA StyleJoseph C. Tsai, Omar A. Saad, Shruti Magesh, Jingyue Xu, Abby C. Lee, Wei Tse Li, Jaideep Chakladar, Mark M. Fuster, Eric Y. Chang, Jessica Wang-Rodriguez, Weg M. Ongkeko. Tobacco Smoke and Electronic Cigarette Vapor Alter Enhancer RNA Expression That Can Regulate the Pathogenesis of Lung Squamous Cell Carcinoma. Cancers. 2021; 13 (16):4225.
Chicago/Turabian StyleJoseph C. Tsai; Omar A. Saad; Shruti Magesh; Jingyue Xu; Abby C. Lee; Wei Tse Li; Jaideep Chakladar; Mark M. Fuster; Eric Y. Chang; Jessica Wang-Rodriguez; Weg M. Ongkeko. 2021. "Tobacco Smoke and Electronic Cigarette Vapor Alter Enhancer RNA Expression That Can Regulate the Pathogenesis of Lung Squamous Cell Carcinoma." Cancers 13, no. 16: 4225.
Patients with underlying cardiovascular conditions are particularly vulnerable to severe COVID-19. In this project, we aimed to characterize similarities in dysregulated immune pathways between COVID-19 patients and patients with cardiomyopathy, venous thromboembolism (VTE), or coronary artery disease (CAD). We hypothesized that these similarly dysregulated pathways may be critical to how cardiovascular diseases (CVDs) exacerbate COVID-19. To evaluate immune dysregulation in different diseases, we used four separate datasets, including RNA-sequencing data from human left ventricular cardiac muscle samples of patients with dilated or ischemic cardiomyopathy and healthy controls; RNA-sequencing data of whole blood samples from patients with single or recurrent event VTE and healthy controls; RNA-sequencing data of human peripheral blood mononuclear cells (PBMCs) from patients with and without obstructive CAD; and RNA-sequencing data of platelets from COVID-19 subjects and healthy controls. We found similar immune dysregulation profiles between patients with CVDs and COVID-19 patients. Interestingly, cardiomyopathy patients display the most similar immune landscape to COVID-19 patients. Additionally, COVID-19 patients experience greater upregulation of cytokine- and inflammasome-related genes than patients with CVDs. In all, patients with CVDs have a significant overlap of cytokine- and inflammasome-related gene expression profiles with that of COVID-19 patients, possibly explaining their greater vulnerability to severe COVID-19.
Abby Lee; Grant Castaneda; Wei Li; Chengyu Chen; Neil Shende; Jaideep Chakladar; Pam Taub; Eric Chang; Weg Ongkeko. COVID-19 Severity Potentially Modulated by Cardiovascular-Disease-Associated Immune Dysregulation. Viruses 2021, 13, 1018 .
AMA StyleAbby Lee, Grant Castaneda, Wei Li, Chengyu Chen, Neil Shende, Jaideep Chakladar, Pam Taub, Eric Chang, Weg Ongkeko. COVID-19 Severity Potentially Modulated by Cardiovascular-Disease-Associated Immune Dysregulation. Viruses. 2021; 13 (6):1018.
Chicago/Turabian StyleAbby Lee; Grant Castaneda; Wei Li; Chengyu Chen; Neil Shende; Jaideep Chakladar; Pam Taub; Eric Chang; Weg Ongkeko. 2021. "COVID-19 Severity Potentially Modulated by Cardiovascular-Disease-Associated Immune Dysregulation." Viruses 13, no. 6: 1018.
Osteoarthritis (OA) is the most common joint disorder in the United States, and the gut microbiome has recently emerged as a potential etiologic factor in OA development. Recent studies have shown that a microbiome is present at joint synovia. Therefore, we aimed to characterize the intra-articular microbiome within osteoarthritic synovia and to illustrate its role in OA disease progression. RNA-sequencing data from OA patient synovial tissue was aligned to a library of microbial reference genomes to identify microbial reads indicative of microbial abundance. Microbial abundance data of OA and normal samples was compared to identify differentially abundant microbes. We computationally explored the correlation of differentially abundant microbes to immunological gene signatures, immune signaling pathways, and immune cell infiltration. We found that microbes correlated to OA are related to dysregulation of two main functional pathways: increased inflammation-induced extracellular matrix remodeling and decreased cell signaling pathways crucial for joint and immune function. We also confirmed that the differentially abundant and biologically relevant microbes we had identified were not contaminants. Collectively, our findings contribute to the understanding of the human microbiome, well-known OA risk factors, and the role microbes play in OA pathogenesis. In conclusion, we present previously undiscovered microbes implicated in the OA disease progression that may be useful for future treatment purposes.
Joseph C. Tsai; Grant Casteneda; Abby Lee; Kypros Dereschuk; Wei Tse Li; Jaideep Chakladar; Alecio F. Lombardi; Weg M. Ongkeko; Eric Y. Chang. Identification and Characterization of the Intra-Articular Microbiome in the Osteoarthritic Knee. International Journal of Molecular Sciences 2020, 21, 8618 .
AMA StyleJoseph C. Tsai, Grant Casteneda, Abby Lee, Kypros Dereschuk, Wei Tse Li, Jaideep Chakladar, Alecio F. Lombardi, Weg M. Ongkeko, Eric Y. Chang. Identification and Characterization of the Intra-Articular Microbiome in the Osteoarthritic Knee. International Journal of Molecular Sciences. 2020; 21 (22):8618.
Chicago/Turabian StyleJoseph C. Tsai; Grant Casteneda; Abby Lee; Kypros Dereschuk; Wei Tse Li; Jaideep Chakladar; Alecio F. Lombardi; Weg M. Ongkeko; Eric Y. Chang. 2020. "Identification and Characterization of the Intra-Articular Microbiome in the Osteoarthritic Knee." International Journal of Molecular Sciences 21, no. 22: 8618.
Although 1 in 9 American men will receive a diagnosis of prostate cancer (PC), most men with this diagnosis will not die from it, as most PCs are indolent. However, there is a subset of patients in which the once-indolent PC becomes metastatic and eventually, fatal. In this study, we analyzed microbial compositions of intratumor bacteria in PC to determine the influence of the microbiome on metastatic growth. Using large-scale RNA-sequencing data and corresponding clinical data, we correlated the abundance of microbes to immune pathways and PC risk factors, identifying specific microbes that either significantly deter or contribute to cancer aggressiveness. Interestingly, most of the microbes we found appeared to play anti-tumor roles in PC. Since these anti-tumor microbes were overrepresented in tumor samples, we believe that microbes thrive in the tumor microenvironment, outcompete cancer cells, and directly mitigate tumor growth by recruiting immune cells. These include Listeria monocytogenes, Methylobacterium radiotolerans JCM 2831, Xanthomonas albilineans GPE PC73, and Bradyrhizobium japonicum, which are negatively correlated with Gleason score, Tumor-Node-Metastasis (TNM) stage, prostate-specific antigen (PSA) level, and Androgen Receptor (AR) expression, respectively. We also identified microbes that contribute to tumor growth and are positively correlated with genomic alterations, dysregulated immune-associated (IA) genes, and prostate cancer stem cells (PCSC) genes.
Jiayan Ma; Aditi Gnanasekar; Abby Lee; Wei Tse Li; Martin Haas; Jessica Wang-Rodriguez; Eric Y. Chang; Mahadevan Rajasekaran; Weg M. Ongkeko. Influence of Intratumor Microbiome on Clinical Outcome and Immune Processes in Prostate Cancer. Cancers 2020, 12, 2524 .
AMA StyleJiayan Ma, Aditi Gnanasekar, Abby Lee, Wei Tse Li, Martin Haas, Jessica Wang-Rodriguez, Eric Y. Chang, Mahadevan Rajasekaran, Weg M. Ongkeko. Influence of Intratumor Microbiome on Clinical Outcome and Immune Processes in Prostate Cancer. Cancers. 2020; 12 (9):2524.
Chicago/Turabian StyleJiayan Ma; Aditi Gnanasekar; Abby Lee; Wei Tse Li; Martin Haas; Jessica Wang-Rodriguez; Eric Y. Chang; Mahadevan Rajasekaran; Weg M. Ongkeko. 2020. "Influence of Intratumor Microbiome on Clinical Outcome and Immune Processes in Prostate Cancer." Cancers 12, no. 9: 2524.
As of 28 August 2020, there have been 5.88 million Coronavirus Disease 2019 (COVID19) cases and 181,000 COVID-19 related deaths in the United States alone. Given the lack of an effective pharmaceutical treatment for COVID-19, the high contagiousness of the disease and its varied clinical outcomes, identifying patients at risk of progressing to severe disease is crucial for the allocation of valuable healthcare resources during this pandemic. Current research has shown that there is a higher prevalence of cardiovascular comorbidities amongst patients with severe COVID-19 or COVID-19-related deaths, but the link between cardiovascular disease and poorer prognosis is poorly understood. We believe that pre-existing immune dysregulation that accompanies cardiovascular disease predisposes patients to a harmful inflammatory immune response, leading to their higher risk of severe disease. Thus, in this project, we aim to characterize immune dysregulation in patients with cardiomyopathy, venous thromboembolism and COVID-19 patients by looking at immune-associated gene dysregulation, immune infiltration and dysregulated immunological pathways and gene signatures.
Grant E Castaneda; Abby C Lee; Wei Tse Li; Chengyu Chen; Jaideep Chakladar; Eric Y. Chang; Weg M. Ongkeko. Comparative analysis of immune-associated genes in COVID-19, cardiomyopathy and venous thromboembolism. 2020, 1 .
AMA StyleGrant E Castaneda, Abby C Lee, Wei Tse Li, Chengyu Chen, Jaideep Chakladar, Eric Y. Chang, Weg M. Ongkeko. Comparative analysis of immune-associated genes in COVID-19, cardiomyopathy and venous thromboembolism. . 2020; ():1.
Chicago/Turabian StyleGrant E Castaneda; Abby C Lee; Wei Tse Li; Chengyu Chen; Jaideep Chakladar; Eric Y. Chang; Weg M. Ongkeko. 2020. "Comparative analysis of immune-associated genes in COVID-19, cardiomyopathy and venous thromboembolism." , no. : 1.
The COVID-19 pandemic caused by the SARS-CoV-2 virus, overlaps with the ongoing epidemics of cigarette smoking and electronic cigarette (e-cig) vaping. However, there is scarce data relating COVID-19 risks and outcome with cigarette or e-cig use. In this study, we mined three independent RNA expression datasets from smokers and vapers to understand the potential relationship between vaping/smoking and the dysregulation of key genes and pathways related to COVID-19. We found that smoking, but not vaping, upregulates ACE2, the cellular receptor that SARS-CoV-2 requires for infection. Both smoking and use of nicotine and flavor-containing e-cigs led to upregulation of pro-inflammatory cytokines and inflammasome-related genes. Specifically, chemokines including CCL20 and CXCL8 are upregulated in smokers, and CCL5 and CCR1 are upregulated in flavor/nicotine-containing e-cig users. We also found genes implicated in inflammasomes, such as CXCL1, CXCL2, NOD2, and ASC, to be upregulated in smokers and these e-cig users. Vaping flavor and nicotine-less e-cigs, however, did not lead to significant cytokine dysregulation and inflammasome activation. Release of inflammasome products, such as IL-1B, and cytokine storms are hallmarks of COVID-19 infection, especially in severe cases. Therefore, our findings demonstrated that smoking or vaping may critically exacerbate COVID-19-related inflammation or increase susceptibility to COVID-19.
Abby Lee; Jaideep Chakladar; Wei Li; Chengyu Chen; Eric Chang; Jessica Wang-Rodriguez; Weg Ongkeko. Tobacco, but Not Nicotine and Flavor-Less Electronic Cigarettes, Induces ACE2 and Immune Dysregulation. International Journal of Molecular Sciences 2020, 21, 5513 .
AMA StyleAbby Lee, Jaideep Chakladar, Wei Li, Chengyu Chen, Eric Chang, Jessica Wang-Rodriguez, Weg Ongkeko. Tobacco, but Not Nicotine and Flavor-Less Electronic Cigarettes, Induces ACE2 and Immune Dysregulation. International Journal of Molecular Sciences. 2020; 21 (15):5513.
Chicago/Turabian StyleAbby Lee; Jaideep Chakladar; Wei Li; Chengyu Chen; Eric Chang; Jessica Wang-Rodriguez; Weg Ongkeko. 2020. "Tobacco, but Not Nicotine and Flavor-Less Electronic Cigarettes, Induces ACE2 and Immune Dysregulation." International Journal of Molecular Sciences 21, no. 15: 5513.