Dr. Premi’s lab focusses on designing novel, preventive and therapeutic strategies against skin cancers, including melanoma.  Currently, there are three main interests of the lab. First is identifying novel therapeutic targets for melanoma and other skin cancers. We are interested in investigating the role of nitric oxide and its metabolites in de-sensitizing the melanomas to current therapeutic modalities. In particular, we focus on the role of nitrosylation and nitration, two posttranslational modifications induced by nitric oxide, in hyperactivating the RAS-MEK-ERK cascade, and also in deactivating antimelanoma immunity. We aim at identifying nitrosylation and nitration driven mechanisms of melanoma progression which will provide potential targets for novel therapeutic approaches against melanoma. Second major focus of the Premi lab is investigating the carcinogenicity of skin pigments. Contrary to their sun-protective role, we discovered that melanin-oxidation by nitric oxide synthase, produces carcinogenic, melanin-carbonyls (MCs). We are investigating the role of melanin-carbonyls in dysregulating melanocytic physiology and promoting melanoma progression and therapy resistance.  Central goal of this research focus is to identify MC-mediated, non-classical regulation of melanoma progression and therapy resistance that could be used as a novel vulnerability against melanoma. The third major research focus of Premi lab is designing next generation, drug like sunscreen compounds. We design and screen novel plant based and synthetic compounds to identify the ones that are non-toxic, non-photosensitizers, potent anti-oxidants, and efficient in blocking incidental and delayed DNA damage induced by exposure to ultraviolet radiation (UV). To achieve this, we have designed several innovative, chemical, and cell-based methods which include measurement of triplet energies of carbonyls and other chemically excited species, DNA ELISA, interaction between DNA and melanin carbonyls, and effect of this interaction on gene expression. Ultimate goal is to design next generation skin-care products which are cosmetic as well as therapeutic. To achieve this, we are funded by NIH, DoD, and also by cosmetic and pharmaceutical industries.