Our research focuses on a protein called Polymerase delta-interacting protein 2 (Poldip2), which plays a crucial role in DNA repair. Previous studies in mice have unveiled that the mutation in Poldip2 leads to a significant reduction in inflammatory responses. Notably, among mice with the mutation in Poldip2, there is a notable decrease in myeloid cell infiltration in the lungs during simulated acute respiratory distress syndrome, while neutrophil cytotoxicity remains unchanged. However, there is a gap in our understanding regarding how single nucleotide polymorphisms (SNPs) in Poldip2 may influence immune regulation in humans. Exploring these SNPs could provide valuable insights into severe infections and multiple organ failure.
Our primary goal is to uncover the relationship between SNPs in Poldip2 and their impact on human health. We plan to delve into genomics, transcriptomics, metabolomics, and proteomics to discover how these SNPs affect gene regulation, protein synthesis, and the metabolism of immune cells.
To investigate our research question as to whether SNPs in Poldip2 is associated with infectious diseases or worsened clinical outcomes, we conducted a variant analysis using total RNA sequencing data from publicly available datasets of infectious patients and individuals with lung cancer. Preliminary results revealed associations between SNPs in Poldip2 and lower gene expression of lung cancer biomarkers.
Moving forward, our project spans 36 months and aims to comprehensively explore the biological impact of Poldip2 SNPs in humans. We plan to use whole-genome sequencing data to validate associations in infectious conditions and organ failure. Integrating multiomic platforms, including genotypic, transcriptomic, metabolomic, and proteomic data, will provide a detailed understanding of how Poldip2 influences clinical outcomes infectious conditions. This knowledge will pave the way for potential interventions to improve patient outcomes.
In terms of public health impact, infectious diseases, particularly sepsis, are major global health challenges with limited treatment options. Poldip2, with its promising outcomes in mice, represents a potential breakthrough. Our research aims to bridge the gap between mouse studies and human applications, uncovering the biological mechanisms behind Poldip2 mutations and exploring interventions that could positively impact patient outcomes in the face of these life-threatening conditions.