Our Science

FIBROBLASTS. REIMAGINED.

We are developing first-in-class therapies that interrupt pathological fibroblast-driven immune signalling.

In their quiescent state, fibroblasts maintain the structural framework for many tissues. They also coordinate normal processes such as wound healing.

However, some activated fibroblasts are also active drivers of disease.

In both the tumour and inflammatory disease microenvironments, we believe activated fibroblast subpopulations act as immune sentinels, directly interacting with immune effector cells to drive disease.

DEFINING DISEASE-DRIVING FIBROBLAST POPULATIONS

Powerful single cell analyses enable us to look at fibroblasts with exquisite precision, revealing subpopulations with diverse functionality.

Analysis of disease tissues has shown that activated fibroblasts map consistently into distinct populations with defined characteristics. These populations appear to be conserved across species, organs and disease contexts.

Our strategy focuses on fibroblast populations implicated in disease, including:

  • Inflammatory Fibroblasts
    • Release chemokines and cytokines to recruit and educate immune cells
  • Myofibroblast
    • Shape the tissue microenvironment via matrix production and remodelling
  • Fibroblast Reticular Cells
    • Initiate and organise lymphoid structures and provide support and education for immune cells

Image thanks to Dr Jenny Marshall and Dr Triin Major.

OUR OPPORTUNITY

To interrupt pathological fibroblast-driven immune signalling across diseases.

For immune oncology this means activating and/or providing T-cell access to the tumour to augment existing therapies.

In inflammatory disease we aim to reduce a chronic inflammatory state, restore the balance of fibroblast quiescence (vs activation), and for example promote mucosal healing and prevent fibrosis.

The discovery of these subpopulations, together with the platform we are building, provides us with the opportunity to develop novel therapeutics capable of reverting the phenotype of pathogenic fibroblasts for the benefit of patients.

 

Zhang et al, Nature Imm 2019
Elyada et al, Cancer Discov, 2019
Wang et al, Nature Comm, 2018
Croft et al, Nature 2019
Korsunsky et al, Biorxiv, 2021
Qian et al, Cell Research, 2020

FIBROBLASTS. REIMAGINED.