A5022953699- Cytokine Signaling Pathways and Interactions
- Immune Cell Function and Interaction
- Inflammasome and immune disorders
- interferon and immune responses
- RNA modifications and cancer
- Acute Myeloid Leukemia Research
- Hematopoietic Stem Cell Transplantation
- Immune cells in cancer
- IL-33, ST2, and ILC Pathways
- Epigenetics and DNA Methylation
- Neonatal Respiratory Health Research
Brigham and Women's Hospital
2022-2024
Harvard University
2022-2024
Jackson Laboratory
2023
Rationale Respiratory virus-induced inflammation is the leading cause of asthma exacerbation, frequently accompanied by induction interferon-stimulated genes ( ISGs ). How asthma-susceptibility modulate cellular response upon viral infection fine-tuning ISG and subsequent airway in genetically susceptible patients remains largely unknown. Objectives To decipher functions gasdermin B (encoded GSDMB ) respiratory lung inflammation. Methods In two independent cohorts, we analysed expression...
Released mitochondrial DNA (mtDNA) in cells activates cGAS-STING pathway, which induces expression of interferon-stimulated genes (ISGs) and thereby promotes inflammation, as frequently seen asthmatic airways. However, whether the genetic determinant, Gasdermin B (GSDMB), most replicated asthma risk gene, regulates this pathway remains unknown. We set out to determine how GSDMB mtDNA-activated subsequent ISGs induction human airway epithelial cells. Using qPCR, ELISA, native polyacrylamide...
Genome-wide association studies (GWAS) have identified dozens of loci associated with chronic obstructive pulmonary disease (COPD) susceptibility; however, the function genes in cell type(s) affected remains poorly understood, partly due to a lack models that recapitulate human alveolar biology. Here, we apply CRISPR interference interrogate nine implicated COPD by GWAS induced pluripotent stem cell–derived type 2 epithelial cells (iAT2s). We find multiple affect iAT2 function, including...
Age-associated clonal hematopoiesis (CH) occurs due to somatic mutations accrued in hematopoietic stem cells (HSCs) that confer a selective growth advantage the context of aging. The mechanisms by which CH-mutant HSCs gain this with aging are not comprehensively understood. Using unbiased transcriptomic approaches, we identified Oncostatin M (OSM) signaling as candidate contributor age-related Dnmt3a-mutant CH. We found from young adult mice (3-6 months old) subjected acute OSM stimulation...