Research Group Mark Mellet, Dr. sc. nat.
Our research focuses on elucidating how pattern recognition receptors and cell death pathways are involved in kindling chronic inflammation at the epidermal barrier and how this drives the pathogenesis of chronic inflammatory dermatological diseases, including psoriasis, pityriasis rubra pilaris and generalized pustular psoriasis.
In particular, we investigate how causative mutations associated with these diseases impact the immune response, including for example; mutations in the keratinocyte signalling molecule CARD14 and the Interleukin-36 cytokine pathway. To address these research questions we implement tools of molecular and cellular biology, -omics approaches, protein biochemistry, light microscopy and in vivo and in vitro models of disease.
Epithelial cells at barrier sites including the skin, gut and mucosal tissue constitute the front line at the host:pathogen interface and mount an immune response to microbial infection that is critical for tailoring effective and prompt immune responses. Like immune cells, epithelial cells express a panoply of pattern recognition receptors, which distinguish highly conserved biochemical features of microbes to discriminate them from host cells. An uncontrolled innate immune response to microbes or danger signals at the epidermal barrier, particularly in genetically susceptible individuals, can lead to sustained activation of pro-inflammatory pathways, promoting chronicity in inflammatory skin disease. Rare and common chronic inflammatory skin diseases reduce the quality of life for sufferers and increase in frequency with age.
Our goal is to elucidate underlying disease mechanisms to define new therapeutic strategies for exploration, in particular for diseases that have an unmet clinical need.
