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Wei Tse Li
Research Service, VA San Diego Healthcare System, San Diego, CA 92161, USA

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Journal article
Published: 23 August 2021 in Cancers
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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.

ACS Style

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 Style

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 (16):4225.

Chicago/Turabian Style

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. 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.

Journal article
Published: 21 July 2021 in Cancers
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The intra-tumor microbiome has recently been linked to epithelial–mesenchymal transition (EMT) in a number of cancers. However, the relationship between EMT and microbes in bladder cancer has not been explored. In this study, we profiled the abundance of individual microbe species in the tumor samples of over 400 muscle invasive bladder carcinoma (MIBC) patients. We then correlated microbe abundance to the expression of EMT-associated genes and genes in the extracellular matrix (ECM), which are key players in EMT. We discovered that a variety of microbes, including E. coli, butyrate-producing bacterium SM4/1, and a species of Oscillatoria, were associated with expression of classical EMT-associated genes, including E-cadherin, vimentin, SNAI2, SNAI3, and TWIST1. We also found significant correlations between microbial abundance and the expression of genes in the ECM, specifically collagens and elastin. Lastly, we found that a large number of microbes exhibiting significant correlations to EMT are also associated with clinical prognosis and outcomes. We further determined that the microbes we profiled were likely not environmental contaminants. In conclusion, we discovered that the intra-tumoral microbiome could potentially play a significant role in the regulation of EMT in MIBC.

ACS Style

Wei Li; Anjali Iyangar; Rohan Reddy; Jaideep Chakladar; Valmik Bhargava; Kyoko Sakamoto; Weg Ongkeko; Mahadevan Rajasekaran. The Bladder Microbiome Is Associated with Epithelial–Mesenchymal Transition in Muscle Invasive Urothelial Bladder Carcinoma. Cancers 2021, 13, 3649 .

AMA Style

Wei Li, Anjali Iyangar, Rohan Reddy, Jaideep Chakladar, Valmik Bhargava, Kyoko Sakamoto, Weg Ongkeko, Mahadevan Rajasekaran. The Bladder Microbiome Is Associated with Epithelial–Mesenchymal Transition in Muscle Invasive Urothelial Bladder Carcinoma. Cancers. 2021; 13 (15):3649.

Chicago/Turabian Style

Wei Li; Anjali Iyangar; Rohan Reddy; Jaideep Chakladar; Valmik Bhargava; Kyoko Sakamoto; Weg Ongkeko; Mahadevan Rajasekaran. 2021. "The Bladder Microbiome Is Associated with Epithelial–Mesenchymal Transition in Muscle Invasive Urothelial Bladder Carcinoma." Cancers 13, no. 15: 3649.

Journal article
Published: 10 June 2021 in Cells
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The implications of the microbiome on Coronavirus disease 2019 (COVID-19) prognosis has not been thoroughly studied. In this study we aimed to characterize the lung and blood microbiome and their implication on COVID-19 prognosis through analysis of peripheral blood mononuclear cell (PBMC) samples, lung biopsy samples, and bronchoalveolar lavage fluid (BALF) samples. In all three tissue types, we found panels of microbes differentially abundant between COVID-19 and normal samples correlated to immune dysregulation and upregulation of inflammatory pathways, including key cytokine pathways such as interleukin (IL)-2, 3, 5-10 and 23 signaling pathways and downregulation of anti-inflammatory pathways including IL-4 signaling. In the PBMC samples, six microbes were correlated with worse COVID-19 severity, and one microbe was correlated with improved COVID-19 severity. Collectively, our findings contribute to the understanding of the human microbiome and suggest interplay between our identified microbes and key inflammatory pathways which may be leveraged in the development of immune therapies for treating COVID-19 patients.

ACS Style

Kypros Dereschuk; Lauren Apostol; Ishan Ranjan; Jaideep Chakladar; Wei Li; Mahadevan Rajasekaran; Eric Chang; Weg Ongkeko. Identification of Lung and Blood Microbiota Implicated in COVID-19 Prognosis. Cells 2021, 10, 1452 .

AMA Style

Kypros Dereschuk, Lauren Apostol, Ishan Ranjan, Jaideep Chakladar, Wei Li, Mahadevan Rajasekaran, Eric Chang, Weg Ongkeko. Identification of Lung and Blood Microbiota Implicated in COVID-19 Prognosis. Cells. 2021; 10 (6):1452.

Chicago/Turabian Style

Kypros Dereschuk; Lauren Apostol; Ishan Ranjan; Jaideep Chakladar; Wei Li; Mahadevan Rajasekaran; Eric Chang; Weg Ongkeko. 2021. "Identification of Lung and Blood Microbiota Implicated in COVID-19 Prognosis." Cells 10, no. 6: 1452.

Journal article
Published: 28 May 2021 in Viruses
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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.

ACS Style

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 Style

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 (6):1018.

Chicago/Turabian Style

Abby 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.

Journal article
Published: 16 November 2020 in International Journal of Molecular Sciences
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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.

ACS Style

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 Style

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 (22):8618.

Chicago/Turabian Style

Joseph 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.

Journal article
Published: 18 September 2020 in Cancers
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An intra-pancreatic microbiota was recently discovered in several prominent studies. Since pancreatic adenocarcinoma (PAAD) is one of the most lethal cancers worldwide, and the intratumor microbiome was found to be a significant contributor to carcinogenesis in other cancers, this study aims to characterize the PAAD microbiome and elucidate how it may be associated with PAAD prognosis. We further explored the association between the intra-pancreatic microbiome and smoking and gender, which are both risk factors for PAAD. RNA-sequencing data from The Cancer Genome Atlas (TCGA) were used to infer microbial abundance, which was correlated to clinical variables and to cancer and immune-associated gene expression, to determine how microbes may contribute to cancer progression. We discovered that the presence of several bacteria species within PAAD tumors is linked to metastasis and immune suppression. This is the first large-scale study to report microbiome-immune correlations in human pancreatic cancer samples. Furthermore, we found that the increased prevalence and poorer prognosis of PAAD in males and smokers are linked to the presence of potentially cancer-promoting or immune-inhibiting microbes. Further study into the roles of these microbes in PAAD is imperative for understanding how a pro-tumor microenvironment may be treated to limit cancer progression.

ACS Style

Jaideep Chakladar; Selena Z. Kuo; Grant Castaneda; Wei Tse Li; Aditi Gnanasekar; Michael Andrew Yu; Eric Y. Chang; Xiao Qi Wang; Weg M. Ongkeko. The Pancreatic Microbiome Is Associated with Carcinogenesis and Worse Prognosis in Males and Smokers. Cancers 2020, 12, 2672 .

AMA Style

Jaideep Chakladar, Selena Z. Kuo, Grant Castaneda, Wei Tse Li, Aditi Gnanasekar, Michael Andrew Yu, Eric Y. Chang, Xiao Qi Wang, Weg M. Ongkeko. The Pancreatic Microbiome Is Associated with Carcinogenesis and Worse Prognosis in Males and Smokers. Cancers. 2020; 12 (9):2672.

Chicago/Turabian Style

Jaideep Chakladar; Selena Z. Kuo; Grant Castaneda; Wei Tse Li; Aditi Gnanasekar; Michael Andrew Yu; Eric Y. Chang; Xiao Qi Wang; Weg M. Ongkeko. 2020. "The Pancreatic Microbiome Is Associated with Carcinogenesis and Worse Prognosis in Males and Smokers." Cancers 12, no. 9: 2672.

Journal article
Published: 05 September 2020 in Cancers
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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.

ACS Style

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 Style

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 (9):2524.

Chicago/Turabian Style

Jiayan 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.

Other
Published: 02 September 2020
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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.

ACS Style

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 Style

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.

Chicago/Turabian Style

Grant 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.

Journal article
Published: 31 July 2020 in International Journal of Molecular Sciences
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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.

ACS Style

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 Style

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 (15):5513.

Chicago/Turabian Style

Abby 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.

Preprint content
Published: 13 July 2020
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COVID-19, caused by the virus SARS-CoV-2, has infected millions worldwide. This pandemic overlaps with the ongoing epidemics of cigarette smoking and electronic cigarette (e-cig) vaping, with over 1 billion smokers and vapers worldwide. However, there is scarce data relating COVID-19 risks and outcome with cigarette or e-cig use. In this study, we mined 3 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-cig led to upregulations of pro-inflammatory cytokine production and expression of genes related to inflammasomes. Vaping flavor-less and nicotine-less e-cig, 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, specifically use of flavored or nicotine-containing e-cigs, may critically exacerbate COVID-19-related inflammation or increase susceptibility to the disease. Further scientific and public health investigations should be undertaken to address these concerning links between COVID-19 and e-cig/smoking.

ACS Style

Abby C. Lee; Jaideep Chakladar; Wei Tse Li; Chengyu Chen; Eric Y. Chang; Jessica Wang-Rodriguez; Weg M. Ongkeko. Tobacco, but not nicotine and flavor-less electronic cigarettes, induces ACE2 and immune dysregulation. 2020, 1 .

AMA Style

Abby C. Lee, Jaideep Chakladar, Wei Tse Li, Chengyu Chen, Eric Y. Chang, Jessica Wang-Rodriguez, Weg M. Ongkeko. Tobacco, but not nicotine and flavor-less electronic cigarettes, induces ACE2 and immune dysregulation. . 2020; ():1.

Chicago/Turabian Style

Abby C. Lee; Jaideep Chakladar; Wei Tse Li; Chengyu Chen; Eric Y. Chang; Jessica Wang-Rodriguez; Weg M. Ongkeko. 2020. "Tobacco, but not nicotine and flavor-less electronic cigarettes, induces ACE2 and immune dysregulation." , no. : 1.

Other
Published: 24 June 2020
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The recent pandemic of Coronavirus Disease 2019 (COVID-19) has placed severe stress on healthcare systems worldwide, which is amplified by the critical shortage of COVID-19 tests. In this study, we propose to generate a more accurate diagnosis model of COVID-19 based on patient symptoms and routine test results by applying machine learning to reanalyzing COVID-19 data from 151 published studies. We aimed to investigate correlations between clinical variables, cluster COVID-19 patients into subtypes, and generate a computational classification model for discriminating between COVID −19 patients and influenza patients based on clinical variables alone. We discovered several novel associations between clinical variables, including correlations between being male and having higher levels of serum lymphocytes and neutrophils. We found that COVID-19 patients could be clustered into subtypes based on serum levels of immune cells, gender, and reported symptoms. Finally, we trained an XGBoost model to achieve a sensitivity of 92.5% and a specificity of 97.9% in discriminating COVID-19 patients from influenza patients. We demonstrated that computational methods trained on large clinical datasets could yield ever more accurate COVID-19 diagnostic models to mitigate the impact of lack of testing. We also presented previously unknown COVID-19 clinical variable correlations and clinical subgroups.

ACS Style

Wei Tse Li; Jiayan Ma; Neil Shende; Grant Castaneda; Jaideep Chakladar; Joseph C. Tsai; Lauren Apostol; Christine O. Honda; Jingyue Xu; Lindsay M. Wong; Tianyi Zhang; Abby Lee; Aditi Gnanasekar; Thomas K. Honda; Selena Z. Kuo; Michael Andrew Yu; Eric Y. Chang; Mahadevan “Raj” Rajasekaran; Weg M. Ongkeko. Using Machine Learning of Clinical Data to Diagnose COVID-19. 2020, 1 .

AMA Style

Wei Tse Li, Jiayan Ma, Neil Shende, Grant Castaneda, Jaideep Chakladar, Joseph C. Tsai, Lauren Apostol, Christine O. Honda, Jingyue Xu, Lindsay M. Wong, Tianyi Zhang, Abby Lee, Aditi Gnanasekar, Thomas K. Honda, Selena Z. Kuo, Michael Andrew Yu, Eric Y. Chang, Mahadevan “Raj” Rajasekaran, Weg M. Ongkeko. Using Machine Learning of Clinical Data to Diagnose COVID-19. . 2020; ():1.

Chicago/Turabian Style

Wei Tse Li; Jiayan Ma; Neil Shende; Grant Castaneda; Jaideep Chakladar; Joseph C. Tsai; Lauren Apostol; Christine O. Honda; Jingyue Xu; Lindsay M. Wong; Tianyi Zhang; Abby Lee; Aditi Gnanasekar; Thomas K. Honda; Selena Z. Kuo; Michael Andrew Yu; Eric Y. Chang; Mahadevan “Raj” Rajasekaran; Weg M. Ongkeko. 2020. "Using Machine Learning of Clinical Data to Diagnose COVID-19." , no. : 1.

Journal article
Published: 21 June 2020 in Cancers
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Hepatocellular carcinoma (HCC) is one of the deadliest cancers in the world. Previous studies have identified the importance of alcohol and hepatitis B (HBV) infection on HCC carcinogenesis, indicating synergy in the methods by which these etiologies advance cancer. However, the specific molecular mechanism behind alcohol and HBV-mediated carcinogenesis remains unknown. Because the microbiome is emerging as a potentially important regulator of cancer development, this study aims to classify the effects of HBV and alcohol on the intratumoral liver microbiome. RNA-sequencing data from The Cancer Genome Atlas (TCGA) were used to infer microbial abundance. This abundance was then correlated to clinical variables and to cancer and immune-associated gene expression, in order to determine how microbial abundance may contribute to differing cancer progression between etiologies. We discovered that the liver microbiome is likely oncogenic after exposure to alcohol or HBV, although these etiological factors could decrease the abundance of a few oncogenic microbes, which would lead to a tumor suppressive effect. In HBV-induced tumors, this tumor suppressive effect was inferred based on the downregulation of microbes that induce cancer and stem cell pathways. Alcohol-induced tumors were observed to have distinct microbial profiles from HBV-induced tumors, and different microbes are clinically relevant in each cohort, suggesting that the effects of the liver microbiome may be different in response to different etiological factors. Collectively, our data suggest that HBV and alcohol operate within a normally oncogenic microbiome to promote tumor development, but are also able to downregulate certain oncogenic microbes. Insight into why these microbes are downregulated following exposure to HBV or alcohol, and why the majority of oncogenic microbes are not downregulated, may be critical for understanding whether a pro-tumor liver microbiome could be suppressed or reversed to limit cancer progression.

ACS Style

Jaideep Chakladar; Lindsay M. Wong; Selena Z. Kuo; Wei Tse Li; Michael Andrew Yu; Eric Y. Chang; Xiao Qi Wang; Weg M. Ongkeko. The Liver Microbiome Is Implicated in Cancer Prognosis and Modulated by Alcohol and Hepatitis B. Cancers 2020, 12, 1642 .

AMA Style

Jaideep Chakladar, Lindsay M. Wong, Selena Z. Kuo, Wei Tse Li, Michael Andrew Yu, Eric Y. Chang, Xiao Qi Wang, Weg M. Ongkeko. The Liver Microbiome Is Implicated in Cancer Prognosis and Modulated by Alcohol and Hepatitis B. Cancers. 2020; 12 (6):1642.

Chicago/Turabian Style

Jaideep Chakladar; Lindsay M. Wong; Selena Z. Kuo; Wei Tse Li; Michael Andrew Yu; Eric Y. Chang; Xiao Qi Wang; Weg M. Ongkeko. 2020. "The Liver Microbiome Is Implicated in Cancer Prognosis and Modulated by Alcohol and Hepatitis B." Cancers 12, no. 6: 1642.

Journal article
Published: 02 June 2020 in Cancers
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The intra-tumor microbiota has been increasingly implicated in cancer pathogenesis. In this study, we aimed to examine the microbiome in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) and determine its compositional differences with relation to age and gender. After grouping 497 LUAD and 433 LUSC patients by age and gender and removing potential contaminants, we identified differentially abundant microbes in each patient cohort vs. adjacent normal samples. We then correlated dysregulated microbes with patient survival rates, immune infiltration, immune and cancer pathways, and genomic alterations. We found that most age and gender cohorts in both LUAD and LUSC contained unique, significantly dysregulated microbes. For example, LUAD-associated Escherichia coli str. K-12 substr. W3110 was dysregulated in older female and male patients and correlated with both patient survival and genomic alterations. For LUSC, the most prominent bacterial species that we identified was Pseudomonas putida str. KT2440, which was uniquely associated with young LUSC male patients and immune infiltration. In conclusion, we found differentially abundant microbes implicated with age and gender that are also associated with genomic alterations and immune dysregulations. Further investigation should be conducted to determine the relationship between gender and age-associated microbes and the pathogenesis of lung cancer.

ACS Style

Lindsay M. Wong; Neil Shende; Wei Tse Li; Grant Castaneda; Lauren Apostol; Eric Y. Chang; Weg M. Ongkeko. Comparative Analysis of Age- and Gender-Associated Microbiome in Lung Adenocarcinoma and Lung Squamous Cell Carcinoma. Cancers 2020, 12, 1447 .

AMA Style

Lindsay M. Wong, Neil Shende, Wei Tse Li, Grant Castaneda, Lauren Apostol, Eric Y. Chang, Weg M. Ongkeko. Comparative Analysis of Age- and Gender-Associated Microbiome in Lung Adenocarcinoma and Lung Squamous Cell Carcinoma. Cancers. 2020; 12 (6):1447.

Chicago/Turabian Style

Lindsay M. Wong; Neil Shende; Wei Tse Li; Grant Castaneda; Lauren Apostol; Eric Y. Chang; Weg M. Ongkeko. 2020. "Comparative Analysis of Age- and Gender-Associated Microbiome in Lung Adenocarcinoma and Lung Squamous Cell Carcinoma." Cancers 12, no. 6: 1447.

Journal article
Published: 21 May 2020 in International Journal of Molecular Sciences
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The COVID-19 pandemic is marked by a wide range of clinical disease courses, ranging from asymptomatic to deadly. There have been many studies seeking to explore the correlations between COVID-19 clinical outcomes and various clinical variables, including age, sex, race, underlying medical problems, and social habits. In particular, the relationship between smoking and COVID-19 outcome is controversial, with multiple conflicting reports in the current literature. In this study, we aim to analyze how smoking may affect the SARS-CoV-2 infection rate. We analyzed sequencing data from lung and oral epithelial samples obtained from The Cancer Genome Atlas (TCGA). We found that the receptor and transmembrane protease necessary for SARS-CoV-2 entry into host cells, ACE2 and TMPRSS2, respectively, were upregulated in smoking samples from both lung and oral epithelial tissue. We then explored the mechanistic hypothesis that smoking may upregulate ACE2 expression through the upregulation of the androgen pathway. ACE2 and TMPRSS2 upregulation were both correlated to androgen pathway enrichment and the specific upregulation of central pathway regulatory genes. These data provide a potential model for the increased susceptibility of smoking patients to COVID-19 and encourage further exploration into the androgen and tobacco upregulation of ACE2 to understand the potential clinical ramifications.

ACS Style

Jaideep Chakladar; Neil Shende; Wei Tse Li; Mahadevan Rajasekaran; Eric Y. Chang; Weg M. Ongkeko. Smoking-Mediated Upregulation of the Androgen Pathway Leads to Increased SARS-CoV-2 Susceptibility. International Journal of Molecular Sciences 2020, 21, 3627 .

AMA Style

Jaideep Chakladar, Neil Shende, Wei Tse Li, Mahadevan Rajasekaran, Eric Y. Chang, Weg M. Ongkeko. Smoking-Mediated Upregulation of the Androgen Pathway Leads to Increased SARS-CoV-2 Susceptibility. International Journal of Molecular Sciences. 2020; 21 (10):3627.

Chicago/Turabian Style

Jaideep Chakladar; Neil Shende; Wei Tse Li; Mahadevan Rajasekaran; Eric Y. Chang; Weg M. Ongkeko. 2020. "Smoking-Mediated Upregulation of the Androgen Pathway Leads to Increased SARS-CoV-2 Susceptibility." International Journal of Molecular Sciences 21, no. 10: 3627.

Journal article
Published: 02 December 2019 in Cancers
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Bladder cancer is one of the most common cancers in the United States, but few advancements in treatment options have occurred in the past few decades. This study aims to identify the most clinically relevant long non-coding RNAs (lncRNAs) to serve as potential biomarkers and treatment targets for muscle invasive bladder cancer (MIBC). Using RNA-sequencing data from 406 patients in The Cancer Genome Atlas (TCGA) database, we identified differentially expressed lncRNAs in MIBC vs. normal tissues. We then associated lncRNA expression with patient survival, clinical variables, oncogenic signatures, cancer- and immune-associated pathways, and genomic alterations. We identified a panel of 20 key lncRNAs that were most implicated in MIBC prognosis after differential expression analysis and prognostic correlations. Almost all lncRNAs we identified are correlated significantly with oncogenic processes. In conclusion, we discovered previously undescribed lncRNAs strongly implicated in the MIBC disease course that may be leveraged for diagnostic and treatment purposes in the future. Functional analysis of these lncRNAs may also reveal distinct mechanisms of bladder cancer carcinogenesis.

ACS Style

Haotian Shen; Lindsay M. Wong; Wei Tse Li; Megan Chu; Rachel A. High; Eric Y. Chang; Jessica Wang-Rodriguez; Weg M. Ongkeko. The Landscape of Long Non-Coding RNA Dysregulation and Clinical Relevance in Muscle Invasive Bladder Urothelial Carcinoma. Cancers 2019, 11, 1919 .

AMA Style

Haotian Shen, Lindsay M. Wong, Wei Tse Li, Megan Chu, Rachel A. High, Eric Y. Chang, Jessica Wang-Rodriguez, Weg M. Ongkeko. The Landscape of Long Non-Coding RNA Dysregulation and Clinical Relevance in Muscle Invasive Bladder Urothelial Carcinoma. Cancers. 2019; 11 (12):1919.

Chicago/Turabian Style

Haotian Shen; Lindsay M. Wong; Wei Tse Li; Megan Chu; Rachel A. High; Eric Y. Chang; Jessica Wang-Rodriguez; Weg M. Ongkeko. 2019. "The Landscape of Long Non-Coding RNA Dysregulation and Clinical Relevance in Muscle Invasive Bladder Urothelial Carcinoma." Cancers 11, no. 12: 1919.

Journal article
Published: 30 August 2019 in Cancers
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Immunotherapy has emerged in recent years as arguably the most effective treatment for advanced hepatocellular carcinoma (HCC), but the failure of a large percentage of patients to respond to immunotherapy remains as the ultimate obstacle to successful treatment. Etiology-associated dysregulation of immune-associated (IA) genes may be central to the development of this differential clinical response. We identified immune-associated genes potentially dysregulated by alcohol or viral hepatitis B in HCC and validated alcohol-induced dysregulations in vitro while using large-scale RNA-sequencing data from The Cancer Genome Atlas (TCGA). Thirty-four clinically relevant dysregulated IA genes were identified. We profiled the correlation of all genomic alterations in HCC patients to IA gene expression while using the information theory-based algorithm REVEALER to investigate the molecular mechanism for their dysregulation and explore the possibility of genome-based patient stratification. We also studied gene expression regulators and identified multiple microRNAs that were implicated in HCC pathogenesis that can potentially regulate these IA genes’ expression. Our study identified potential key pathways, including the IL-7 signaling pathway and TNFRSF4 (OX40)- NF-κB pathway, to target in immunotherapy treatments and presents microRNAs as promising therapeutic targets for dysregulated IA genes because of their extensive regulatory roles in the cancer immune landscape.

ACS Style

Wei Tse Li; Angela E. Zou; Christine O. Honda; Hao Zheng; Xiao Qi Wang; Tatiana Kisseleva; Eric Y. Chang; Weg M. Ongkeko. Etiology-Specific Analysis of Hepatocellular Carcinoma Transcriptome Reveals Genetic Dysregulation in Pathways Implicated in Immunotherapy Efficacy. Cancers 2019, 11, 1273 .

AMA Style

Wei Tse Li, Angela E. Zou, Christine O. Honda, Hao Zheng, Xiao Qi Wang, Tatiana Kisseleva, Eric Y. Chang, Weg M. Ongkeko. Etiology-Specific Analysis of Hepatocellular Carcinoma Transcriptome Reveals Genetic Dysregulation in Pathways Implicated in Immunotherapy Efficacy. Cancers. 2019; 11 (9):1273.

Chicago/Turabian Style

Wei Tse Li; Angela E. Zou; Christine O. Honda; Hao Zheng; Xiao Qi Wang; Tatiana Kisseleva; Eric Y. Chang; Weg M. Ongkeko. 2019. "Etiology-Specific Analysis of Hepatocellular Carcinoma Transcriptome Reveals Genetic Dysregulation in Pathways Implicated in Immunotherapy Efficacy." Cancers 11, no. 9: 1273.

Journal article
Published: 15 August 2019 in Cancers
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Papillary thyroid carcinoma (PTC) variants exhibit different prognosis, but critical characteristics of PTC variants that contribute to differences in pathogenesis are not well-known. This study aims to characterize dysregulated immune-associated and cancer-associated genes in three PTC subtypes to explore how the interplay between cancer and immune processes causes differential prognosis. RNA-sequencing data from The Cancer Genome Atlas (TCGA) were used to identify dysregulated genes in each variant. The dysregulation profiles of the subtypes were compared using functional pathways clustering and correlations to relevant clinical variables, genomic alterations, and microRNA regulation. We discovered that the dysregulation profiles of classical PTC (CPTC) and the tall cell variant (TCPTC) are similar and are distinct from that of the follicular variant (FVPTC). However, unique cancer or immune-associated genes are associated with clinical variables for each subtype. Cancer-related genes MUC1, FN1, and S100-family members were the most clinically relevant in CPTC, while APLN and IL16, both immune-related, were clinically relevant in FVPTC. RAET-family members, also immune-related, were clinically relevant in TCPTC. Collectively, our data suggest that dysregulation of both cancer and immune associated genes defines the gene expression landscapes of PTC variants, but different cancer or immune related genes may drive the phenotype of each variant.

ACS Style

Jaideep Chakladar; Wei Tse Li; Michael Bouvet; Eric Y. Chang; Jessica Wang-Rodriguez; Weg M. Ongkeko. Papillary Thyroid Carcinoma Variants are Characterized by Co-dysregulation of Immune and Cancer Associated Genes. Cancers 2019, 11, 1179 .

AMA Style

Jaideep Chakladar, Wei Tse Li, Michael Bouvet, Eric Y. Chang, Jessica Wang-Rodriguez, Weg M. Ongkeko. Papillary Thyroid Carcinoma Variants are Characterized by Co-dysregulation of Immune and Cancer Associated Genes. Cancers. 2019; 11 (8):1179.

Chicago/Turabian Style

Jaideep Chakladar; Wei Tse Li; Michael Bouvet; Eric Y. Chang; Jessica Wang-Rodriguez; Weg M. Ongkeko. 2019. "Papillary Thyroid Carcinoma Variants are Characterized by Co-dysregulation of Immune and Cancer Associated Genes." Cancers 11, no. 8: 1179.

Journal article
Published: 07 January 2019 in International Journal of Molecular Sciences
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Cancer stem cells (CSCs) have been shown as a distinct population of cancer cells strongly implicated with resistance to conventional chemotherapy. Metformin, the most widely prescribed drug for diabetes, was reported to target cancer stem cells in various cancers. In this study, we sought to determine the effects of metformin on head and neck squamous cell carcinoma (HNSCC). CSCs and non-stem HNSCC cells were treated with metformin and cisplatin alone, and in combination, and cell proliferation levels were measured through MTS assays. Next, potential targets of metformin were explored through computational small molecule binding analysis. In contrast to the reported effects of metformin on CSCs in other cancers, our data suggests that metformin protects HNSCC CSCs against cisplatin in vitro. Treatment with metformin resulted in a dose-dependent induction of the stem cell genes CD44, BMI-1, OCT-4, and NANOG. On the other hand, we observed that metformin successfully decreased the proliferation of non-stem HNSCC cells. Computational drug–protein interaction analysis revealed mitochondrial complex III to be a likely target of metformin. Based on our results, we present the novel hypothesis that metformin targets complex III to reduce reactive oxygen species (ROS) levels, leading to the differential effects observed on non-stem cancer cells and CSCs.

ACS Style

Selena Z. Kuo; Christine O. Honda; Wei Tse Li; Thomas K. Honda; Elizabeth Kim; Xabier Altuna; Eric Abhold; Jessica Wang-Rodriguez; Weg M. Ongkeko. Metformin Results in Diametrically Opposed Effects by Targeting Non-Stem Cancer Cells but Protecting Cancer Stem Cells in Head and Neck Squamous Cell Carcinoma. International Journal of Molecular Sciences 2019, 20, 193 .

AMA Style

Selena Z. Kuo, Christine O. Honda, Wei Tse Li, Thomas K. Honda, Elizabeth Kim, Xabier Altuna, Eric Abhold, Jessica Wang-Rodriguez, Weg M. Ongkeko. Metformin Results in Diametrically Opposed Effects by Targeting Non-Stem Cancer Cells but Protecting Cancer Stem Cells in Head and Neck Squamous Cell Carcinoma. International Journal of Molecular Sciences. 2019; 20 (1):193.

Chicago/Turabian Style

Selena Z. Kuo; Christine O. Honda; Wei Tse Li; Thomas K. Honda; Elizabeth Kim; Xabier Altuna; Eric Abhold; Jessica Wang-Rodriguez; Weg M. Ongkeko. 2019. "Metformin Results in Diametrically Opposed Effects by Targeting Non-Stem Cancer Cells but Protecting Cancer Stem Cells in Head and Neck Squamous Cell Carcinoma." International Journal of Molecular Sciences 20, no. 1: 193.

Journal article
Published: 13 March 2018 in Neoplasia
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Though bladder urothelial carcinoma is the most common form of bladder cancer, advances in its diagnosis and treatment have been modest in the past few decades. To evaluate miRNAs as putative disease markers for bladder urothelial carcinoma, this study develops a process to identify dysregulated miRNAs in cancer patients and potentially stratify patients based on the association of their microRNAome phenotype to genomic alterations. Using RNA sequencing data for 409 patients from the Cancer Genome Atlas, we examined miRNA differential expression between cancer and normal tissues and associated differentially expressed miRNAs with patient survival and clinical variables. We then correlated miRNA expressions with genomic alterations using the Wilcoxon test and REVEALER. We found a panel of six miRNAs dysregulated in bladder cancer and exhibited correlations to patient survival. We also performed differential expression analysis and clinical variable correlations to identify miRNAs associated with tobacco smoking, the most important risk factor for bladder cancer. Two miRNAs, miR-323a and miR-431, were differentially expressed in smoking patients compared to nonsmoking patients and were associated with primary tumor size. Functional studies of these miRNAs and the genomic features we identified for potential stratification may reveal underlying mechanisms of bladder cancer carcinogenesis and further diagnosis and treatment methods for urothelial bladder carcinoma.

ACS Style

Wei Tse Li; Hao Zheng; Vincent Nguyen; Jessica Wang-Rodriguez; Weg M. Ongkeko. Functional Genomics Profiling of Bladder Urothelial Carcinoma MicroRNAome as a Potential Biomarker. Neoplasia 2018, 20, 364 -373.

AMA Style

Wei Tse Li, Hao Zheng, Vincent Nguyen, Jessica Wang-Rodriguez, Weg M. Ongkeko. Functional Genomics Profiling of Bladder Urothelial Carcinoma MicroRNAome as a Potential Biomarker. Neoplasia. 2018; 20 (4):364-373.

Chicago/Turabian Style

Wei Tse Li; Hao Zheng; Vincent Nguyen; Jessica Wang-Rodriguez; Weg M. Ongkeko. 2018. "Functional Genomics Profiling of Bladder Urothelial Carcinoma MicroRNAome as a Potential Biomarker." Neoplasia 20, no. 4: 364-373.