A5016422217- Neonatal Respiratory Health Research
- Congenital Diaphragmatic Hernia Studies
- Infectious Diseases and Mycology
- Vascular Tumors and Angiosarcomas
- Plant Disease Resistance and Genetics
- RNA Interference and Gene Delivery
- Respiratory viral infections research
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Tissue Engineering and Regenerative Medicine
- Respiratory Support and Mechanisms
- Pediatric health and respiratory diseases
- Epigenetics and DNA Methylation
- Immune Response and Inflammation
- Extracellular vesicles in disease
- Virus-based gene therapy research
- Diabetes and associated disorders
- Mesenchymal stem cell research
- Phagocytosis and Immune Regulation
- MicroRNA in disease regulation
- Advanced biosensing and bioanalysis techniques
- IL-33, ST2, and ILC Pathways
- COVID-19 Clinical Research Studies
- Immune Cell Function and Interaction
- Erythrocyte Function and Pathophysiology
- Chronic Obstructive Pulmonary Disease (COPD) Research
Children's Hospital of Philadelphia
2024-2025
University of Pennsylvania
2017-2025
California Institute for Regenerative Medicine
2017-2024
Philadelphia University
2024
California University of Pennsylvania
2019-2024
United States University
2022
Lung Institute
2020-2022
University of Michigan
2019
University of California, Davis
2018
University of California, San Francisco
2012-2017
Red blood cells detect and bind cell-free nucleic acids, contributing to anemia immune cell activation during acute inflammation.
Abstract Lipid nanoparticles for delivering mRNA therapeutics hold immense promise the treatment of a wide range lung-associated diseases. However, lack effective methodologies capable identifying pulmonary delivery profile chemically distinct lipid libraries poses significant obstacle to advancement therapeutics. Here we report implementation barcoded high-throughput screening system as means identify lung-targeting efficacy cationic, degradable lipid-like materials. We combinatorially...
Abstract The ionizable lipidoid is a key component of lipid nanoparticles (LNPs). Degradable lipidoids containing extended alkyl branches have received tremendous attention, yet their optimization and investigation are underappreciated. Here, we devise an in situ construction method for the combinatorial synthesis degradable branched (DB) lipidoids. We find that appending branch tails to inefficacious via linkers boosts mRNA delivery efficiency up three orders magnitude. Combinatorial...
Lipid nanoparticles (LNPs) have emerged as pivotal vehicles for messenger RNA (mRNA) delivery to hepatocytes upon systemic administration and antigen-presenting cells following intramuscular injection. However, achieving mRNA non-hepatocytes remains challenging without the incorporation of targeting ligands such antibodies, peptides, or small molecules. Inspired by comb-like polymeric architecture, here we utilized a multiarm-assisted design construct library 270 dendron-like degradable...
H1N1 influenza virus infection induces dramatic and permanent alveolar remodeling mediated by p63
Disruption of pulmonary vascular homeostasis is a central feature viral pneumonia, wherein endothelial cell (EC) death and subsequent angiogenic responses are critical determinants the outcome severe lung injury. A more granular understanding fundamental mechanisms driving reconstitution endothelium necessary to facilitate therapeutic repair. Here, we demonstrated that TGF-β signaling through TGF-βR2 (transforming growth factor–β receptor 2) activated in ECs upon influenza infection, mice...
Abstract Inflammation induced by lung infection is a double-edged sword, moderating both anti-viral and immune pathogenesis effects; the mechanism of latter not fully understood. Previous studies suggest vasculature involved in tissue injury. Here, we report that expression Sparcl1, secreted matricellular protein, upregulated pulmonary capillary endothelial cells (EC) during influenza-induced Endothelial overexpression SPARCL1 promotes detrimental inflammation, with inducing ‘M1-like’...
Macrophages are integral components of the innate immune system, playing a dual role in host defense during infection and pathophysiological states. contribute to responses aid combatting various infections, yet their production abundant proinflammatory cytokines can lead uncontrolled inflammation worsened tissue damage. Therefore, reducing macrophage-derived cytokine release represents promising approach for treating acute chronic inflammatory disorders. However, limited macrophage-specific...
Alveolar type-2 (AT2) cells are necessary for the lung's regenerative response to epithelial insults such as influenza. However, current methods expand these rely on mesenchymal co-culture, complicating possibility of transplantation following acute injury. Here we developed several mesenchyme-free culture conditions that promote growth murine AT2 organoids. Transplanting dissociated organoids into influenza-infected mice demonstrated engraft and either proliferate or unexpectedly adopt a...
Coordinated efforts between macrophages and epithelia are considered essential for wound healing, but the macrophage-derived molecules responsible repair poorly defined. This work demonstrates that lung rely upon Trefoil factor 2 to promote epithelial proliferation following damage caused by sterile wounding, Nippostrongylus brasiliensis or Bleomycin sulfate. Unexpectedly, presence of T, B, ILC populations was not macrophage-driven repair. Instead, conditional deletion TFF2 in...
Epithelial cell organoids have increased opportunities to probe questions on tissue development and disease in vitro for therapeutic transplantation. Despite their potential, current protocols grow these almost exclusively depend culture within 3D Matrigel, which limits defined conditions, introduces animal components, results heterogenous (i.e., shape, size, composition). Here, a method is described that relies hyaluronic acid hydrogels the generation expansion of lung alveolar...
While the lung bears significant regenerative capacity, severe viral pneumonia can chronically impair function by triggering dysplastic remodeling. The connection between these enduring changes and chronic disease remains poorly understood. We recently described emergence of tuft cells within Krt5 + regions after influenza injury. Using bulk single-cell transcriptomics, we characterized delineated multiple distinct cell populations that arise following clearance. Distinct from intestinal...
Lung injury activates epithelial stem or progenitor cells for alveolar repair and regeneration. Unraveling the origin fate of injury-induced progenitors is crucial elucidating lung mechanisms. Here, we report that p63-expressing emerge upon bleomycin-induced mouse injury. Single-cell RNA sequencing clonal analysis reveal these p63+ proliferate rapidly differentiate into type 1 2 through different trajectories. Dual recombinase-mediated sequential genetic-lineage tracing demonstrates...
Acute respiratory distress syndrome is associated with a robust inflammatory response that damages the vascular endothelium, impairing gas exchange. While restoration of microcapillaries critical to avoid mortality, therapeutic targeting this process requires greater understanding endothelial repair mechanisms. Here, we demonstrate lung endothelium possesses substantial regenerative capacity and lineage tracing reveals native source after influenza injury. Ablation chicken ovalbumin upstream...
Abstract Maintenance of the cellular boundary between airway and alveolar compartments during homeostasis after injury is essential to prohibit pathological plasticity which can reduce respiratory function. Lung disease induce either functional epithelial regeneration or dysplastic formation keratinized epithelium does not efficiently contribute gas exchange. Here we show that Sox2 preserves cell identity prevents fate changes into tissue keratinization following lung injury. Loss in leads a...