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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.
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.
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.
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 StyleJaideep 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 StyleJaideep 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.
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 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.
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 StyleLindsay 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 StyleLindsay 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.