Francesca Capon
Lab overview
My lab is mainly interested in the genetic and immune basis of diseases that present with severe skin inflammation. Some of these conditions (e.g. eczema) are common and have a very significant impact on quality of life. Others are rare but can affect multiple organs (autoinflammatory syndromes) or become potentially life-threatening (generalized pustular psoriasis).
We use a variety of genetic and computational approaches to identify disease drivers and determine whether they can be blocked with existing drugs. Where some treatments are available, we seek to characterize the causes of incomplete efficacy and adverse events.
Research Projects
Gene identification in severe skin inflammation
Common inflammatory skin disorders such as eczema have a profound impact on quality of life. Meanwhile, rare forms of psoriasis (e.g. generalised pustular psoriasis) are potentially life-threatening.
We have been investigating the causes of these conditions by combining genetic approaches (genome-wide association studies, whole-exome sequencing) with the in-vitro and ex-vivo characterization of disease alleles. This integrated strategy has been very productive. For example, it has enabled us to identify IL-36 as a key disease driver and therapeutic target in generalised pustular psoriasis.
Mechanisms underlying response to biologics
Biologic drugs that target specific disease drivers have revolutionised the treatment of skin diseases such as psoriasis. However, significant variability in drug response is observed across affected individuals.
To better understand the mechanisms underlying drug-induced remission and relapse, we are using single-cell omics to investigate early response to biologics. We have recently identified a fibroblasts population that rapidly reduces in frequency after treatment of psoriasis with IL-23/IL-17 blockers. To build on this work, we are currently investigating the cell states mediating the effects of IL-4/IL-13 inhibitors in atopic dermatitis (eczema).
Genetic basis of paediatric vasculitis
The term vasculitis refers to a group of conditions where inflammation of the blood vessels can damage organs such as the skin, lung and kidney. The causes of the disease are not fully understood, so there is an unmet need for personalised and targeted treatment.
We are working in collaboration with Dr Kelly Brown to identify new genetic determinants for the disease. We are using whole-exome sequencing to characterise early-onset cases that are likely caused by monogenic mutations.
Lab members
Jingrong Shi, PhD student
Ha Quan Nguyen, MSc Student
Austin Burroughs, Research Assistant
Nusaiba Shahid, Undergraduate student
Joshua Rubin, Postdoctoral fellow
Recent publications
1. Smail A, Dand N, Liu X, The APRICOT and PLUM study group, Baudry D, Burden AD, Griffiths CEM, Pink AE, Reynolds NJ, Warren RB, Visvanathan S, Barker JN, Løset M, Smith CH, Capon F. Mendelian randomization identifies OX40 as a potential mediator of the effects of cigarette smoking in palmoplantar pustulosis. Br J Dermatol 193:1240-1242 2025
2. Hernandez-Cordero A, Thomas L, Smail A, Lim ZQ, Saklatvala JR, Chung R, Curtis CJ, Baum P, Visvanathan S, Burden AD, Cooper HL, Dunnill G, Griffiths CE, Levell NJ, Parslew R, Reynolds NJ, Wahie S, Warren RB, Wright A; APRICOT and PLUM Study Team; Simpson M, Hveem K, Barker JN, Dand N, Loset M, Smith CH, Capon F. A genome-wide meta-analysis of palmoplantar pustulosis implicates Th2 responses and cigarette smoking in disease pathogenesis. J Allergy Clin Immunol 154:657-665.
3. Francis L, McCluskey D, Ganier C, Jiang T, Du-Harpur X, Gabriel J, Dhami P, Kamra Y, Visvanathan S, Barker JN, Smith CH, Capon F*, Mahil SK*. Single-cell analysis of psoriasis resolution demonstrates an inflammatory fibroblast state targeted by IL-23 blockade. Nature Comms 2024 15:913 (*joint senior and corresponding author).
4. McCluskey D, Benzian-Olsson N, Mahil SK, Hassi NK, Wohnhaas CT; APRICOT and PLUM study team, Burden AD, Griffiths CE, Ingram JR, Levell NJ, Parslew R, Pink AE, Reynolds NJ, Warren RB, Visvanathan S, Baum P, Barker JN, Smith CH, Capon F. Single-cell analysis implicates Th17 to Th2 cell plasticity in the pathogenesis of palmoplantar pustulosis. J Allergy Clin Immunol. 2022 150:882-893
5. Vergnano M, Grys K, Benzian-Olsson N, Mahil SK, Chaloner C, August S, Burden AD, Choon SE, Cooper H, Reynolds N, Wahie S, Warren RB, Wright A, The APRICOT and PLUM study team, Huffmeier U, Baum P, Visvanathan S, Barker J, Smith C, Capon F. Loss-of-function myeloperoxidase mutations are associated with increased neutrophil counts and pustular skin disease. Am J Hum Genet, 2020 107:539-543.
(Full publication list available at https://tinyurl.com/CaponPubMed)