Papers by Carolina Garcia de Alba Rivas
F1000 - Post-publication peer review of the biomedical literature, 2013
D108. NEW INSIGHTS IN CELL FATE, REGENERATIVE MEDICINE, iPSCs, AND MSCs, May 1, 2022
We here present COOBoostR (https://github.com/SWJ9385/COOBoostR), a computational method designed... more We here present COOBoostR (https://github.com/SWJ9385/COOBoostR), a computational method designed for the putative prediction of tissue-or cell-of-origin of various cancer types. COOBoostR leverages regional somatic mutation density information and chromatin mark features to be applied to an extreme gradient boosting-based machine-learning algorithm. COOBoostR ranks chromatin marks from various tissue and cell types which best explain the somatic mutation density landscape of any sample of interest. Through integrating either ChIP-seq based chromatin data or bulk/single cell chromatin accessibility data along with regional somatic mutation density data derived from normal cells/tissue, precancerous lesions, and cancer types, we show that COOBoostR outperforms existing random forest-based methods in prediction speed with comparable or better tissue or cell-of-origin prediction performance. In addition, our results suggest a dynamic somatic mutation accumulation at the normal tissue o...
F1000 - Post-publication peer review of the biomedical literature, 2016
Cell Reports
Highlights d Alveolar organoid cells engraft into the alveolar space d Transplanted lung alveolar... more Highlights d Alveolar organoid cells engraft into the alveolar space d Transplanted lung alveolar cells have transcriptional signature of native AT2 cells d Transplanted alveolar cells proliferate and retain organoidforming capacity d Organoid cells undergo changes to transitional cell states upon transplantation
F1000 - Post-publication peer review of the biomedical literature, 2009
The FASEB Journal, 2010
"Abstract Rationale: Fibrocytes are progenitor cells characterized by the simultaneous expre... more "Abstract Rationale: Fibrocytes are progenitor cells characterized by the simultaneous expression of mesenchymal, monocyte and hematopoietic stem cell markers. We previously documented their presence in lungs of patients with idiopathic pulmonary fibrosis. However, the mechanisms involved in their migration, subsequent homing and local role remain unclear. Matrix metalloproteinases (MMPs) facilitate cell migration and have been implicated in the pathogenesis of pulmonary fibrosis. Objectives: To evaluate the expression and role of matrix metalloproteinases in human fibrocytes. Methods: Fibrocytes were purified from CD14+ monocytes and cultured for eight days; purity of fibrocytes cultures was ≥95% determined by flow cytometry. Conditioned media and total RNA were collected and the expression of MMP-1, -2, -7, -8 and -9 was evaluated by real time PCR. Protein synthesis was examined using a Multiplex assay, Western blot, fluorescent immunocytochemistry and confocal microscopy. MMP-2 and -9 enzymatic activities were evaluated by gelatin zymography. Migration was assessed using collagen I coated Boyden chambers. SDF-1α and PDGF-B were used as chemoattractant with or without a specific MMP-8 inhibitor. Measurements and Main Results: Fibrocytes showed gene and protein expression of MMP-2, MMP-9, MMP-8 and MMP-7. MMP-2 and MMP-9 enzymatic activities were also demonstrated by gelatin zymography. Likewise, we found co-localization of MMP-8 and MMP-7 with type I collagen in fibrocytes. Fibrocytes migration toward PDGF-B or SDF-1α in collagen I coated Boyden chambers was significantly reduced by a specific MMP-8 inhibitor. "
A well-tolerated and cost-effective oral drug that blocks SARS-CoV-2 growth and dissemination wou... more A well-tolerated and cost-effective oral drug that blocks SARS-CoV-2 growth and dissemination would be a major advance in the global effort to reduce COVID-19 morbidity and mortality. Here, we show that the oral FDA-approved drug nitazoxanide (NTZ) significantly inhibits SARS-CoV-2 viral replication and infection in different primate and human cell models including stem cell-derived human alveolar epithelial type 2 cells. Furthermore, NTZ synergizes with remdesivir, and it broadly inhibits growth of SARS-CoV-2 variants B.1.351 (beta), P.1 (gamma), and B.1617.2 (delta) and viral syncytia formation driven by their spike proteins. Strikingly, oral NTZ treatment of Syrian hamsters significantly inhibits SARS-CoV-2-driven weight loss, inflammation, and viral dissemination and syncytia formation in the lungs. These studies show that NTZ is a novel host-directed therapeutic that broadly inhibits SARS-CoV-2 dissemination and pathogenesis in human and hamster physiological models, which supp...
SummaryThe alveolar epithelial type 2 cell (AEC2) is the facultative progenitor of lung alveoli t... more SummaryThe alveolar epithelial type 2 cell (AEC2) is the facultative progenitor of lung alveoli tasked to maintain distal lung homeostasis. AEC2 dysfunction has been implicated in the pathogenesis of a number of pulmonary diseases, including idiopathic pulmonary fibrosis (IPF), highlighting the importance of human in vitro models of the alveolar epithelium. However, AEC2-like cells captured in cell culture have yet to be directly compared to their in vivo counterparts at single cell resolution. Here, we apply single cell RNA sequencing to perform head-to-head comparisons between the global transcriptomes of freshly isolated primary (1°) adult human AEC2s, their isogenic cultured progeny, and human iPSC-derived AEC2s (iAEC2s) cultured in identical conditions. We find each population occupies a distinct transcriptomic space with both types of cultured AEC2s (1° and iAEC2s) exhibiting similarities to and differences from freshly purified 1° cells. Across each cell type, we find an inve...
Coronavirus disease 2019 (COVID-19) is the latest respiratory pandemic resulting from zoonotic tr... more Coronavirus disease 2019 (COVID-19) is the latest respiratory pandemic resulting from zoonotic transmission of severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2). Severe symptoms include viral pneumonia secondary to infection and inflammation of the lower respiratory tract, in some cases causing death. We developed primary human lung epithelial infection models to understand responses of proximal and distal lung epithelium to SARS-CoV-2 infection. Differentiated air-liquid interface cultures of proximal airway epithelium and 3D organoid cultures of alveolar epithelium were readily infected by SARS-CoV-2 leading to an epithelial cell-autonomous proinflammatory response. We validated the efficacy of selected candidate COVID-19 drugs confirming that Remdesivir strongly suppressed viral infection/replication. We provide a relevant platform for studying COVID-19 pathobiology and for rapid drug screening against SARS-CoV-2 and future emergent respiratory pathogens.One Se...
PLOS ONE, 2016
Idiopathic pulmonary fibrosis (IPF) is a progressive and lethal disease of unknown etiology. A gr... more Idiopathic pulmonary fibrosis (IPF) is a progressive and lethal disease of unknown etiology. A growing body of evidence indicates that it may result from an aberrant activation of alveolar epithelium, which induces the expansion of the fibroblast population, their differentiation to myofibroblasts and the excessive accumulation of extracellular matrix. The mechanisms that activate the alveolar epithelium are unknown, but several studies indicate that smoking is the main environmental risk factor for the development of IPF. In this study we explored the effect of cigarette smoke on the gene expression profile and signaling pathways in alveolar epithelial cells. Lung epithelial cell line from human (A549), was exposed to cigarette smoke extract (CSE) for 1, 3, and 5 weeks at 1, 5 and 10% and gene expression was evaluated by complete transcriptome microarrays. Signaling networks were analyzed with the Ingenuity Pathway Analysis software. At 5 weeks of exposure, alveolar epithelial cells acquired a fibroblast-like phenotype. At this time, gene expression profile revealed a significant increase of more than 1000 genes and deregulation of canonical signaling pathways such as TGF-β and Wnt. Several profibrotic genes involved in EMT were over-expressed, and incomplete EMT was observed in these cells, and corroborated in mouse (MLE-12) and rat (RLE-6TN) epithelial cells. The secretion of activated TGF-β1 increased in cells exposed to cigarette smoke, which decreased when the integrin alpha v gene was silenced. These findings suggest that the exposure of alveolar epithelial cells to CSE induces the expression and release of a variety of profibrotic genes, and the activation of TGF-β1, which may explain at least partially, the increased risk of developing IPF in smokers.
F1000 - Post-publication peer review of the biomedical literature, 2012
F1000 - Post-publication peer review of the biomedical literature, 2010
F1000 - Post-publication peer review of the biomedical literature, 2011
F1000 - Post-publication peer review of the biomedical literature, 2013
F1000 - Post-publication peer review of the biomedical literature, 2014
F1000 - Post-publication peer review of the biomedical literature, 2010
F1000 - Post-publication peer review of the biomedical literature, 2009
F1000 - Post-publication peer review of the biomedical literature, 2009
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Papers by Carolina Garcia de Alba Rivas