Novel Host-Response Biomarker Diagnostics for Invasive Aspergillosis

PROJECT SUMMARY/ABSTRACT Invasive aspergillosis (IA) is a severe and frequent complication in immunocompromised patients. Earlier diagnosis expedites appropriate antifungal therapy and drastically improves clinical outcomes and patient survival. However, current pathogen-based fungal testing is often hampered by poor accuracy, delayed results, and a requirement for invasive sampling. This proposal will overcome these limitations by establishing novel, rapid, noninvasive diagnostic and prognostic biomarkers for IA based on host transcriptional responses to infection. Moreover, the project will ensure that these biomarkers can accurately function in the presence of diverse immunosuppressive regimens. Building on the candidate’s published work, the main goals of this project are three-fold: 1.) To derive and optimize a diagnostic host gene expression signature of IA from banked samples of a large established repository; 2.) To enroll and serially sample subjects with fungal infection to derive a prognostic host gene expression signature of IA and measure response to treatment; and 3.) To develop the candidate into a uniquely qualified independent translational physician-scientist, advancing non-invasive diagnostic and precision medicine tools for infection in immunocompromised patients. This research is critical for NIAID’s mission to better understand and treat fungal infections, particularly as Aspergillus species have become increasingly recognized as critical fungal pathogens. Additionally, the project will develop the candidate’s expertise in biological pathway analysis and fungal immunology, diagnostic test development and evaluation, and biomarker implementation. The results of this project will also generate preliminary data for the next step in this program of research, progressing through the translational pathway to develop and implement a clinically validated host-based diagnostic and prognostic tool for IA. The candidate’s research and career development will be guided by an invested and experienced mentorship team at a research-intensive institution with abundant resources in infectious diseases, translational research, transplantation, genomics, and precision medicine.