Chronic inflammatory diseases, such as atopic dermatitis, exhibit substantial heterogeneity, where patients follow diverse disease trajectories despite sharing the same clinical diagnosis. This variability arises from complex interactions between genetic predisposition, environmental factors, and nonlinear biological processes. The mechanisms through which these interactions generate distinct disease states remain poorly understood.

My PhD research investigates the origins of disease heterogeneity through mathematical modelling. Using chronic atopic dermatitis as a model system, we developed a mechanistic mathematical model that integrates key regulatory processes governing epithelial barrier function, antimicrobial defence, inflammation, Th2 immune activation, and keratinocyte differentiation. The model reproduced clinically observed disease trajectory subtypes and identifies the mechanisms underlying each of the subtypes. By integrating the identified key mechanisms with gene ontology analyses and human genetic data, we generated subtype-specific hypotheses linking genetic variation to long-term disease outcomes.

The model analysis for chronic atopic dermatitis required development of mathematical methods for analysing piecewise-smooth dynamical systems with switch-like regulatory mechanisms. My thesis developed it as a general  analytical workflow to systematically characterise equilibrium and transient behaviours, enabling exhaustive exploration of complex regulatory networks beyond the limitations of numerical simulations.

I am currently applying this modelling approach to another chronic disease, periodontal disease, demonstrating its applicability for uncovering mechanisms underlying disease heterogeneity across different chronic inflammatory conditions. Together, this research establishes mechanistic mathematical modelling as a framework for understanding how interactions between molecular mechanisms and environmental influences give rise to diverse disease trajectories, while generating experimentally testable hypotheses and analytical tools applicable to a broad range of biological systems.