Donald Ingber

Payment for services (e.g., consulting fees, honoraria, paid authorship)

Lung-on-a-Chip Disease Models for Efficacy Testing

PROJECT NARRATIVE Our goal is to create in vitro models of influenza virus infection using microfluidic human Organ-on-a-Chip (Organ Chip) culture devices that recapitulate clinical features of the disease, and demonstrate that they can be used for drug screening and discovery of new antiviral therapeutics. Human Lung Airway Chips and Lung Alveolus Chips lined by cells from normal donors or patients with chronic obstructive pulmonary disease (COPD) that we have previously shown to mimic in vivo organ-level pathophysiology will be linked by their vascular channels to model clinical features of influenza virus infection, including viral replication and shedding, release of characteristic inflammatory mediators, recruitment of circulating immune cells, and development of pulmonary edema in vitro. This novel influenza disease model will then be linked to human Liver Chips that carry out drug metabolism to conduct preclinical efficacy and safety testing of existing antiviral drugs, identify new potential drug targets, and discover new therapeutics that target the host response to infection, rather than the virus itself.