Molecular mechanisms of cellular crosstalk in skin regeneration and cancer

Although an association between tissue damage, chronic inflammation and cancer is wellestablished, little is known about the underlying molecular mechanisms. During previous research, I identified molecules that play important roles in mediating the cellular crosstalk between keratinocytes, fibroblasts and immune cells during cutaneous inflammation and cancer initiation. Here, I aim to investigate the function of the danger-associated molecule high-mobility group box 1 (HMGB1) in immune cell infiltration in skin homeostasis, regeneration and tumour formation. I previously demonstrated that HMGB1 is upregulated during skin trauma and in wound-induced cutaneous tumours, in both men and mice (Hoste et al., 2015). I now wish to study immune cell infiltration in the presence or absence of HMGB1 in various cell-types during the different stages of skin wound healing and neoplasia.

In a second aim, I will focus on the role of ADAMTS4 in fibroblast activation during cutaneous wound healing and wound-induced tumour formation and maintenance. Fibroblasts are the main cell-type of connective tissue and emerging data show essential roles for fibroblasts in mediating tumour initiation and propagation. I previously identified ADAMTS4 as a top upregulated gene in cancerassociated fibroblasts versus normal and inflammatory skin fibroblasts and I now aim to study the function of ADAMTS4 in regenerative and tumour-inducing inflammation.