A non-canonical role of Myc in programming basal cells as sentinels of upper airway immunity during influenza infection
HIGHLIGHTS:
- Influenza infection induces Myc upregulation specifically in upper airway sentinel basal progenitors
- Myc drives basal cell secretion of CXCL10 to recruit cytotoxic CD8⁺ NKT effectors
- MYC-dependent CXCL10–CXCR3 axis establishes persistent upper airway antiviral immunity
My current research is guided by the hypothesis that viral infection of the larynx activates neurosensory cells, remodels both afferent and efferent nerves, and contributes to mucosal inflammation and hypersensitivity. To test this hypothesis, I am utilizing a combination of mouse genetics, whole tissue clearing and imaging, and single-cell transcriptomics. Findings from this study will reveal the neuroimmune mechanism that mediate postviral laryngeal inflammation and sensorimotor neuropathies.
Cellular heterogeneity and patterning strategies as revealed by upper respiratory epithelium single cell atlas
Mucosal surfaces lined by epithelial cells are essential elements of the respiratory tract, effective not only as a first-line physical barrier against chronic external threats, but also for host immune defense, and injury repair. Here, using single cell RNAseq combined with spatial validation, we present a comprehensive atlas of the mouse upper respiratory epithelium. This work serves as a valuable atlas for hypothesis-driven work into responses to environmental insults, genetic mutations, and infectious diseases.
Physical forces, such as mechanical stress, are essential for tissue homeostasis and influence gene expression of cells. In particular, the fibroblast has demonstrated sensitivity to extracellular matrices with assumed adaptation upon various mechanical loads. The purpose of this study was to compare the vocal fold fibroblast genotype, known for its unique mechanically stressful tissue environment, with cellular counterparts at various other anatomic locales to identify differences in functional gene expression profiles. By using bulk RNA-seq technology, we identified differentially expressed gene programs (DEseq2) among seven normal human fibroblast primary cell lines from healthy cadavers, which included: vocal fold, trachea, lung, abdomen, scalp, upper gingiva, and soft palate.
Piezo1-expressing vocal fold epithelia modulate remodeling via effects on self-renewal and cytokeratin differentiation
Mechanoreceptors are implicated as functional afferents within mucosa of the airways and the recent discovery of mechanosensitive channels Piezo1 and Piezo2 has proved essential for cells of various mechanically sensitive tissues. However, the role for _Piezo1/2 _ in vocal fold (VF) mucosal epithelia, a cell that withstands excessive biomechanical insult, remains unknown. The purpose of this study was to test the hypothesis that Piezo1 is required for VF mucosal repair pathways of epithelial cell injury. Utilizing cell-based assays within genetically-engineered murine tissue, we demonstrated a role for Piezo1-expressing VF epithelia in regulating self-renewal via effects on p63 transcription and YAP subcellular translocation—altering cytokeratin differentiation.
This review article improved understanding of iSLN innervation and corresponding mechanotransduction events to help shed light upon a variety of pathological reflex responses, including persistent cough, dysphonia, and laryngospasm.
