Langerhans Cell Histiocytosis: (Collaboration with Drs. Allen and McClain’s Groups in the Baylor College of Medicine)
Langerhans Cell Histiocytosis (LCH) is the most common of the rare group of disorders that constitute histiocytosis, with an approximate incidence of three to seven cases per million, predominantly but not exclusively in children. LCH was thought to result from an accumulation of epidermal Langerhans cells (LCs). The identification of a langerin+ DC lineage independent of LC by our group has lead us to hypothesize that LCH was due to an accumulation of interstitial langerin+ DCs, and not LCs, and can be characterized by dysregulated molecular pathways in the former (Merad et al. Nature Reviews Immunology 2008). The recent identification of the mutation BRAFV600E that occurs in more than 50% of LCH lesions has lead us to develop the first model of BRAFV600E LCH-like disease (Berres et al. JEM 2014). Current studies in the laboratory are using the LCH mouse models and obtained patient samples to explore BRAFV600E –driven molecular mechanisms that lead to DC accumulation in LCH lesions and to identify novel therapeutic modalities for the treatment of LCH.