A diverse array of network modalities (e.g. genomic, organellar, cytoskeletal, inter-cellular, extra-cellular, microbiomic) interacting across multiple scales regulate airway remodelling. This includes a variety of differentially expressed genes, multiple cell types, etc. This complexity, disease heterogeneity, and lack of mechanistic understanding means the molecular logic that governs asthma severity across scales remains elusive. The lab is developing multiscale methodologies to understand the multiscale dynamics of asthma pathophysiology at an individual level.
Organoids are high-throughput 3D in vitro cultures that have lower parametric complexity than animal models but reflect human physiology more closely. Airway organoids capture structural components and markers of human airways robustly. Importantly, these organoids can be created using gene edited cells to test the systems-level impact of singular or multiple mutations. The lab is currently developing the next generation of airway organoids that will be used to test mechanistic predictions.
Virtual or digital patients are built using architectural, physiological, or genomic characteristics derived from the actual patients and serve as their digital twins. Virtual patients allow us to understand disease progression at a personal level. As such, they can be employed to tailor therapies based on the profile of the patient. The lab is developing platform technology that will help create virtual patients for a range of respiratory diseases.
The virtual patients can be used to conduct virtual or digital clinical trials that have the potential to help explain responder vs non-responder effects, for example. These digital trials need validation at intracellular, cellular, organ, and patient levels. This is a key challenge successfully addressing which will result in high technological and societal impact. The lab is developing applications to conduct these digital trials and validate their predictions against clinical data in a systematic way.