Marila Cordeiro-Stone

My research is focused on mechanisms of DNA replication, DNA repair, and DNA damage activation of cell cycle checkpoints in human cells. Inherited and acquired defects in the molecular network of protection of genetic stability are associated with increased risk for mutations underlying cancer pathogenesis. My laboratory studies how human cells succeed in completing genome duplication, even in the presence of DNA lesions that block the replication machinery. DNA damage tolerance depends on the replication fork protection complex avoiding the collapse of stalled forks and mechanisms to replicate past the template lesion. Our studies have been focused primarily on the response of human cells to DNA damage caused by ultraviolet (UV) radiation. Current efforts are directed toward the identification of key molecular events that contribute to the development of skin cancers in areas exposed to sunlight. The component of solar radiation that is most damaging to the skin is represented by the wavelengths of UV that penetrate the Earth atmosphere (UVB and UVA). Therefore, it is our goal to translate past research experience with biological effects of UVC in cultured fibroblasts to clinically relevant cell types. In this regard, my laboratory is collaborating with a group of basic scientists and clinical investigators with expertise in different aspects of DNA repair, replication, and checkpoint control in UV-exposed human cells, as well as the epidemiology and pathogenesis of malignant melanoma. Such a multidisciplinary effort is needed for reaching a better understanding of how several DNA metabolic pathways and cellular responses to DNA damage are coordinated in the target cell for skin melanomas (melanocytes) or carcinomas (keratinocytes) and how these protective barriers might be compromised during cancer development.