The overarching goal of my research program is to elucidate the molecular mechanisms of ultraviolet radiation (UVR)-induced melanomagenesis. The major etiological risk factor for the majority of melanomas has long been known to be UVR, yet the underlying mechanisms largely remain elusive. The hunt for melanoma-initiating genes has remained focused on UVR-induced DNA mutations. However, several studies have fueled the notion that mechanisms other than direct DNA damage are also important for UVR-induced initiation and progression of melanoma. To find clues to these mechanisms, we profiled the melanocytic gene expression response to UVR exposure while in their normal skin microenvironment (Nature 469:548). To circumvent the considerable challenge of studying a cell type in vivo that constitutes a tiny fraction of the mammalian skin, we developed a mouse model in which melanocytes can be both imaged in vivo and highly purified by virtue of tetracycline-inducible, melanocyte-specific GFP expression (iDct-GFP mice). This novel mouse model provides an invaluable tool to explore melanocyte and melanoma biology while residing within their natural microenvironment.

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