We lack effective treatments and preventions for many of the most challenging infectious diseases, many of which disproportionately impact those in low- and middle-income countries or traditionally marginalized communities.
To help address this, we have established and enabled multi-group, multi-country partnerships to deploy and adapt cutting-edge genomic tools. By examining how cells dynamically alter their states, individually and collectively, during disease and/or its resolution in acute and chronic infections—e.g., tuberculosis, HIV/SHIV, hepatitis, malaria, leprosy, flu, SARS-CoV-2, and ebola—we have uncovered cellular and molecular features of pathogen control or pathology to potentiate or counteract, respectively. Illustratively, in tuberculosis, we identified a functional role for cytotoxic CD8 and hybrid type1-type17 T cells in control of infection in the lung and links between mast, plasma, and endothelial cell abundance (type-2 immune responses) and bacterial burden. We have also built methods for examining pathogens within individual host cells to define their dynamic interdependence and identify potentially restrictive host factors.
We are currently working to identify the drivers of common host responses to distinct perturbations and their targetability, as well as the impact of different interventions (e.g., vaccines).