A5017478777- Tissue Engineering and Regenerative Medicine
- Single-cell and spatial transcriptomics
- Neonatal Respiratory Health Research
- 3D Printing in Biomedical Research
- Electrospun Nanofibers in Biomedical Applications
- Pulmonary Hypertension Research and Treatments
- Wound Healing and Treatments
- Extracellular vesicles in disease
- Mesenchymal stem cell research
- Respiratory Support and Mechanisms
- Tracheal and airway disorders
- Liver physiology and pathology
- Gene Regulatory Network Analysis
- Bioinformatics and Genomic Networks
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Dermatologic Treatments and Research
- Medical Imaging and Pathology Studies
- MicroRNA in disease regulation
- Immune cells in cancer
- Cell Image Analysis Techniques
- Angiogenesis and VEGF in Cancer
- Chronic Obstructive Pulmonary Disease (COPD) Research
- Cardiac Arrest and Resuscitation
- Additive Manufacturing and 3D Printing Technologies
- interferon and immune responses
Yale University
2014-2025
National Student Clearinghouse Research Center
2021
Yale New Haven Hospital
2020
Massachusetts Institute of Technology
2014-2016
Because adult lung tissue has limited regeneration capacity, transplantation is the primary therapy for severely damaged lungs. To explore whether can be regenerated in vitro, we treated lungs from rats using a procedure that removes cellular components but leaves behind scaffold of extracellular matrix retains hierarchical branching structures airways and vasculature. We then used bioreactor to culture pulmonary epithelium vascular endothelium on acellular matrix. The seeded displayed...
Cellular diversity of the lung endothelium has not been systematically characterized in humans. We provide a reference atlas human endothelial cells (ECs) to facilitate better understanding phenotypic and composition comprising endothelium.We reprocessed control single-cell RNA sequencing (scRNAseq) data from 6 datasets. EC populations were through iterative clustering with subsequent differential expression analysis. Marker genes validated by fluorescent microscopy situ hybridization....
Single-cell network analysis demonstrates species-conserved functional roles for pulmonary alveolar cell types.
Abstract Dysregulated immune responses against the SARS-CoV-2 virus are instrumental in severe COVID-19. However, signatures associated with immunopathology poorly understood. Here we use multi-omics single-cell analysis to probe dynamic hospitalized patients stable or progressive course of COVID-19, explore V(D)J repertoires, and assess cellular effects tocilizumab. Coordinated profiling gene expression cell lineage protein markers shows that S100A hi /HLA-DR lo classical monocytes...
Chronic obstructive pulmonary disease (COPD) is a leading cause of death worldwide, however our understanding cell specific mechanisms underlying COPD pathobiology remains incomplete. Here, we analyze single-cell RNA sequencing profiles explanted lung tissue from subjects with advanced or control lungs, and validate findings using lungs mice exposed to 10 months cigarette smoke, isolated human alveolar epithelial cells, functional in vitro models, situ hybridization immunostaining samples....
Single-cell RNA-sequencing data has revolutionized our ability to understand of the patterns cell-cell and ligand-receptor connectivity that influence function tissues organs. However, quantification visualization these in a way informs tissue biology are major computational epistemological challenges. Here, we present Connectome, software package for R which facilitates rapid calculation interactive exploration signaling network topologies contained single-cell data. Connectome can be used...
Adult mammalian skin wounds heal by forming fibrotic scars. We report that full-thickness injuries of reindeer antler (velvet) regenerate, whereas back forms scar. Single-cell multi-omics reveal uninjured velvet fibroblasts resemble human fetal fibroblasts, express inflammatory mediators mimicking pro-fibrotic adult and rodent fibroblasts. Consequently, injury elicits site-specific immune responses: amplify myeloid infiltration maturation during repair, adopt an immunosuppressive phenotype...
Recent years have seen the release of several toolsets that reveal cell-cell interactions from single-cell data. However, all existing approaches leverage mean celltype gene expression values, and do not preserve fidelity original Here, we present NICHES (Niche Interactions Communication Heterogeneity in Extracellular Signaling), a tool to explore extracellular signaling at truly level.NICHES allows embedding ligand-receptor signal proxies visualize heterogeneous archetypes within cell...
ABSTRACT In vitro models that recapitulate the liver's structural and functional complexity could prolong hepatocellular viability function to improve platforms for drug toxicity studies understanding liver pathophysiology. Here, stereolithography (SLA) was employed fabricate hydrogel scaffolds with open channels designed post‐seeding perfused culture of primary hepatocytes form 3D structures in a bioreactor. Photopolymerizable polyethylene glycol‐based hydrogels were fabricated coupled...
Fibrotic hypersensitivity pneumonitis (FHP) is a debilitating interstitial lung disease driven by incompletely understood immune mechanisms.
Cell-based therapies have shown promise for treating myriad chronic pulmonary diseases through direct application of epithelial progenitors or by way engineered tissue grafts whole organs. To elucidate environmental effects on regenerative outcomes in vitro, here, we isolate and culture a population pharmacologically expanded basal cells (peBCs) from rat tracheas. At peak marker expression, simultaneously split peBCs into four vitro platforms: organoid, air-liquid interface (ALI), trachea,...
Abstract A dysregulated immune response against the SARS-CoV-2 virus plays a critical role in severe COVID-19. However, molecular and cellular mechanisms by which causes lethal immunopathology are poorly understood. Here, we utilize multiomics single-cell analysis to probe dynamic responses patients with stable or progressive manifestations of COVID-19, assess effects tocilizumab, an anti-IL-6 receptor monoclonal antibody. Coordinated profiling gene expression cell lineage protein markers...
Decellularized organs are now established as promising scaffolds for whole-organ regeneration. For this work to reach therapeutic practice, techniques and apparatus necessary doing human-scale clinically applicable organ cultures. We have designed constructed a bioreactor system capable of accommodating whole human or porcine lungs, we describe in study relevant technical details, means assembly operation, validation. The reactor has an artificial diaphragm that mimics the conditions found...
Abstract Single-cell RNA-sequencing data can revolutionize our understanding of the patterns cell-cell and ligand-receptor connectivity that influence function tissues organs. However, quantification visualization these are major computational epistemological challenges. Here, we present Connectome , a software package for R which facilitates rapid calculation, interactive exploration, signaling network topologies contained in single-cell data. be used with any reference set known...
Abstract Engineered whole lungs may one day expand therapeutic options for patients with end-stage lung disease. However, the feasibility of ex vivo regeneration remains limited by inability to recapitulate mature, functional alveolar epithelium. Here, we modulate multimodal components epithelial type 2 cell (AEC2) niche in decellularized scaffolds order guide AEC2 behavior regeneration. First, endothelial cells coordinate fibroblasts, presence soluble growth and maturation factors, promote...
Abstract To date, few studies have detailed the tumor microenvironment (TME) of Ewing sarcoma (EwS). The TME has a vital role in cancer survival and progression with implications drug resistance immune escape. By performing spatially resolved transcriptomic analysis primary treatment-naïve EwS samples, we discovered greater stromal enrichment localized tumors compared to metastatic tumors. Through spatial ligand-receptor analysis, show that enriched regions harbor unique extracellular matrix...
Abstract Hypoxemia impairs cardiopulmonary function. We investigated pulmonary artery remodeling in mice exposed to chronic hypoxia for up five weeks and quantified associated changes cardiac lung function, without or with subsequent normoxic recovery the absence presence of exercise pharmacological intervention. Hypoxia-induced stiffening proximal stemmed primarily from adventitial collagen, which resulted part altered inter-cellular signaling phenotypic mural smooth muscle cells...
Abstract Objective: To date, the response rate of immunotherapy in Ewing sarcoma (EwS) has been poor. The tumor immune microenvironment (TME) a vital role cancer survival and progression with implications drug resistance escape. However, there is lack understanding TME EwS. Although recent single-cell RNA sequencing EwS cells have revealed heterogenous transcriptional landscape distinct subsets cell populations EwS, little known about spatial organization microenvironmental niches Methods:...