Abstract
Altered skin pigmentation is one of the most common dermatologic disorders that affect 1 in 3 people worldwide. The hair follicle melanocyte stem cell niche is the main melanocyte reservoir in the skin and a better understanding of the mechanisms regulating pigmentation is critical for designing novel therapy strategies against pigmentation disorders. We are developing novel genetic tools to study and target the hair follicle stem cell niche. Recently, we have shown how in the DP compartment the gene Sox2 is a key regulator of hair growth by controlling the BMP-mediated mesenchymal-epithelial crosstalk between the DP niche cells and the stem cell progeny. Now, we have identified a color switch in the pelage of DP-specific Sox2 knock down mice and observed abnormal BMP cell signaling within the melanocyte compartment of the HF. This phenotype, suggests that Sox2 and BMP signaling are also master regulators of the melanocyte stem cell niche. Interestingly, data from human keratinocyte and melanocyte co-cultures shows that BMP signaling can regulate melanogenesis and melanin transfer. In addition, we are studying melanocyte migration at the functional level in vitro and in vivo and our data indicates that BMP signaling significantly modulates migration of melanocytes. Finally, we are using our hair follicle stem cell niche in vivo and in vitro models to study two of the most common consequence of skin aging: hair loss and pigmentation disorders. We are using novel senescence markers to investigate how senescence affects different cell types within the hair follicle during male pattern baldness and hair greying in human biopsies and mouse models. Identifying the mechanisms resulting in hair loss and hair de-pigmentation during ageing will allow for the development of translational programs to target pathways and molecules with large therapeutic and commercial interest.
Biography
Carlos Clavel received his BS and MS in Biological Sciences from Saint Louis University in the US. He finished his PhD training in the Cell Therapy lab at the University of Navarra, Spain. Thanks to a collaboration with the laboratory of Dr. Catherine Verfaillie, he had the opportunity of working with Multipotent Adult Progenitor Cells in her groundbreaking laboratories of Minnesota (US) and Leuven (Belgium). At that time, he was focused on the tremendous differentiation potential of human adult stem cells. His research then shifted to understanding how stem cells are instructed to display their potential, and he subsequently joined Dr. Michael Rendl’s laboratory at Mount Sinai School of Medicine in New York where his research focused on the transcriptional control of the hair inducing fate of Dermal Papilla niche cells. Carlos has recently joined IMB as a Project Leader where he is starting up his own research group focusing on understanding the regulation of the hair follicle stem cell niche and its implication in novel therapies for skin pigmentation disorders.