Translational Framework for Tuberculosis

The long-term goal of this project is to develop a general translational systems pharmacology simulation framework to help evaluate new treatment intervention hypotheses from novel findings in basic and/or preclinical research for testing in small, focused TB clinical trials. The simulation will combine multilevel systems biology and population PK-PD approaches to predict responses to various multi-drug treatments. Our work will explore genetic factors, host and drug interactions driving disease evolution, bacterial adaptation, and infection response to therapy. The project aims to 1) develop a unified systems pharmacology framework; 2) explore networks of proteins, cells, and other potential biomarkers driving variability in clinical response; and 3) develop hypotheses for innovative dosing strategies to provide optimal drug therapies for patients, which may later be tested in focused, small-scale clinical trials.