Keloids are common fibrotic skin lesions known to occur only in humans due to abnormal wound healing in susceptible individuals. They are characterized by excessive dermal fibroblast proliferation and deposition of type I collagen. The incidence of keloids is very high among dark-skinned individuals (~15-20% of people of African descent are believed to be affected), who form keloids at least 15 times more frequently than light-skinned people, suggesting that genetic and/or epigenetic factors make a strong contribution to keloid disease. However, the genetic and epigenetic mechanisms involved in keloid formation in susceptible individuals are unknown. Although keloids are common, they are relatively understudied compared to other dermatologic disorders and as a result, they continue to be one of the most challenging dermatological conditions to treat effectively. As keloids grow in size, they are often symptomatic, causing major discomfort, pain, severe itching, psychological and/or physical distress that may significantly impair the patient’s quality of life. Large keloids are typically treated by surgical removal; unfortunately, they regrow in nearly 100% of the cases without any adjuvant therapy and are difficult to treat. Suppression of excessive collagen secretion by keloid fibroblasts and reduction in their proliferation rate are the current goals of keloid therapy. The primary treatment of smaller keloids as well as post-surgical adjuvant therapy for keloids often involves intralesional injections or superficial application of corticosteroids. However, several recent reports suggest that a significant number of keloid patients are refractory to steroids or exhibit worsening of keloids upon steroid therapy, although the molecular determinants of the response of keloids to steroid therapy are unknown. Hence, our immediate goal is to use unbiased genomic sequencing-based approaches to identify and characterize the genetic and epigenetic mechanisms involved in keloid formation and their differential responses to steroid therapy.