Khan Lab: Engineering Human Pre-Clinical Models

Overview

Pathological tissue remodelling is a defining feature of ageing and disease. Across conditions including cancer, cardiovascular disease, and haematological disorders, coordinated interactions between stromal, immune, and vascular compartments drive structural and functional changes in tissues. While these processes are essential for repair, their dysregulation leads to fibrosis, chronic inflammation, and progressive loss of function. These changes worsen outcomes, and limit the effectiveness of new treatment modalities.

Despite its central role in disease progression and therapeutic failure, tissue remodelling remains poorly understood and inadequately targeted. The major translational bottleneck has been human model systems that capture the myriad cell types needed to effectively model phenomenon like fibrosis and inflammation.

Our research unpicks mechanisms that drive fibrosis and inflammation using human organoid platforms that capture the complexity of immune responses within and across tissues and diseases.

Research Themes

Mechanisms of pathological tissue remodelling

We investigate how multicellular interactions between stromal, immune, and vascular compartments drive tissue dysfunction in disease and across disease contexts.

Our work focuses on non-canonical signalling pathways that coordinate fibrosis, inflammation, and immune regulation. We are particularly interested in mechanisms that drive treatment resistance and disease persistence through the tissue microenvironment.

Human multi-compartment organoid systems

We develop complex human organoid platforms that recapitulate key features of native tissue architecture and cellular composition.

These systems integrate stromal, immune, and endothelial compartments within controlled 3D environments, enabling direct interrogation of processes that are inaccessible in conventional in vitro or animal models. Our work spans bone marrow, cardiovascular, and linked multi-organoid systems to study both local and systemic responses to injury and disease.

Therapeutic targeting of tissue remodelling

We apply these platforms to identify and validate therapeutic strategies that modulate pathological tissue remodelling.

This includes defining how the tissue microenvironment shapes disease progression and treatment response, and evaluating combination strategies that target both diseased cells and their surrounding niche.

Approach

The foundation of our work are complex human models that can be benchmarked to primary human biology, enabling new and exciting insights into the onset and progression of disease. We can combine deep phenotyping (RNA sequencing, multi-omics, high dimensional flow cytometry and imaging) with functional validation and machine learning to unpick mechanisms in experimentally tractable models of human biology.