How we are seeking to understand disease mechanisms and develop biomarker-enabled precision medicine and new therapeutic interventions.

Skin disease is very common, with a profound, under-recognised impact on health and society. In order to meet the need for better diagnostics and new, cost-effective treatments, we are seeking to understand disease mechanisms and thereby develop biomarker-enabled precision medicine and new therapeutic interventions.

We are developing novel precision therapeutics, biomarkers and co-diagnostics for genetic, inflammatory and neoplastic skin disease and lead a major international bioresource for the study of skin disease and outcomes associated with skin disease.

Our research is delivered via four programmes:

  • Programme 1: Advanced cell and biologic therapies for rare skin diseases
  • Programme 2: Integrated cutaneous bioresource and data warehousing
  • Programme 3: Proof-of-principle precision medicine studies in inflammatory skin disease
  • Programme 4: Translational antibody therapeutic development for melanoma.

Example projects

  • Interleukin-36 as a target for therapeutic intervention in generalised pustular psoriasis. Having demonstrated that abnormal IL-36 activity is a key disease driver in generalised pustular psoriasis (GPP), a rare but potentially life-threatening condition presenting with painful skin pustules, high fever and fatigue, we showed that IL-36 inhibition has profound anti-inflammatory effects in patient skin and in models (Mahil SK. et al, 2017. Sci Transl Med, 9:2514). This research has informed the development of IL-36 inhibitors and Boehringer-Ingelheim has now reported strong efficacy in clinical trials of GPP exemplifying the power of genetic studies in drug discovery.

 

  • Developing a new class of immunotherapy to treat melanoma. We have pioneered IgE immunotherapy for melanoma and other solid cancers (Pellizzari G. et al., J Immunother Cancer (2021) 9(6):e002140) from conception, revealing how IgE functions against tumours, through to translation into early clinical testing and commercialisation, launching a spinout company that has secured substantial investment to deliver licensed IgE drug products to patients. This new cancer immunotherapy class is expected to deliver major therapeutic benefit to people with skin cancer in the next 5 years.

 

  • Clinical testing of cell and gene-therapy based therapies in patients with recessive dystrophic epidermolysis bullosa (RDEB) First-in-man and early phase clinical trials of gene and cell-based therapies for patients with RDEB have demonstrated safety (Lwin SM. et al., JCI Insight (2019) 4:e12624) and early efficacy, improving patients’ symptoms such as pain, itch, and poor wound healing (Petrof G. et al., J Invest Dermatol (2015)135:2319-2321), and leading to larger clinical trials and industrial partnerships. We are now launching a new national clinical trial in children with RDEB, called “Mission EB”, with £4.3m funding from NHS England so that we can see whether the cells might become part of clinical care in the NHS.