Molecular mechanisms of cellular crosstalk in skin regeneration and cancer

01 January 2017 → 31 December 2017
Research Foundation - Flanders (FWO)
Research disciplines
  • Natural sciences
    • Other biological sciences
    • Other natural sciences
skin regeneration
Project description

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.