Grant: Project Grant

For the past 17 years, my laboratory has been studying skin diseases caused by abnormalities of melanocytes, the cells that produce melanin pigment that protects our skin from the harmful effects of ultraviolet light in the sun. More than 50 million people worldwide develop a severe disfiguring disease called vitiligo, which is caused by patchy loss of normal skin color due to death of melanocytes. In addition, more than 300 thousand of people develop melanoma each year in the world, which is caused by the opposite change in the melanocytes, i.e. uncontrolled multiplication of cancerous melanocytes. The exact mechanisms leading to the opposite fates of melanocytes in these two diseases are unclear. There is an urgent need to develop better therapies for vitiligo and melanoma. My laboratory recently found a new type of innate immune cells in the surroundings of the melanocytes in the skin, the CLEC12B+ macrophages. These cells are important participants of the immune response to pathogens attacking our skin, such as bacteria, allergens and viruses. They are also required for stopping the immune responses when the pathogens are eliminated, so that the immunologic balance is restored, tissue injuries are repaired, and damaged cells are replenished. My lab found that in vitiligo, there is a shortage of these cells, where as in melanoma, there is an excess. In culture dishes, these macrophages secrete growth factors that can enhance melanocyte survival, but suppress professional killer cells, such as the natural killer cells and killer lymphocytes. Therefore, I speculate that deficiency of these macrophages is the reason for vitiligo development, and that over population of these cells have the opposite effect, that is, unchecked growth of the melanoma cells. In this project, I will test these hypotheses using cultured cells in petri dishes and in animal models. The results generated will help develop more effective therapies for vitiligo and melanoma.