Research Questions:
What is the prevalence of CHIP in SCAP patients? How does CHIP influence SCAP progression, outcomes, and prognosis? What are the mechanisms through which CHIP impacts SCAP?
Objectives:
Using UK Biobank’s large-scale genomic and clinical data, validating the association between CHIP and SCAP outcomes.
Identify CHIP-related mutations (e.g., DNMT3A, TET2, ASXL1) linked to adverse SCAP outcomes.
Utilize transcriptomic, metabolomic, and animal model data to investigate the mechanistic impact of CHIP on SCAP progression.
Scientific Rationale:
Severe community-acquired pneumonia (SCAP) is a leading cause of mortality worldwide. Clonal hematopoiesis of indeterminate potential (CHIP) is characterized by somatic mutations associated with hematologic cancers, even in the absence of overt disease. Our preliminary study of 200 CAP patients from a hospital in Shanghai revealed that CHIP is prevalent in severe cases and independently associated with poor prognosis. However, the cohort’s limited geographic and demographic scope necessitates validation in larger, more diverse populations.
This project leverages UK Biobank’s large-scale dataset to confirm the relationship between CHIP and SCAP progression across a broader population. Beyond correlation, we will use our transcriptomic and metabolomic data to probe how CHIP influences immune responses. To further explore the underlying mechanisms, we will employ experimental studies, including mouse models, to directly examine the mechanistic impact of CHIP on SCAP development and progression.
This comprehensive research strategy aims to validate our initial findings and uncover the biological mechanisms underpinning CHIP’s role in SCAP pathogenesis, providing a foundation for targeted therapeutic strategies to improve patient outcomes.
