The organelles of the endocytic pathway serve many ‘housekeeping’ functions such as taking up nutrients, controlling signaling pathways and degrading unwanted macromolecules. In addition, these organelles are involved in a diverse range of more specific cellular functions.
The major goals of our research are to gain a better understanding of the biogenesis and functions of two such specialized endosomal organelles: exosomes, which are secreted from multivesicular bodies, and the lysosome-related organelles called melanosomes which synthesize the pigment melanin.
Our studies are carried out using a variety of human and mouse cell types in culture by combining electron microscopy with light microscopy, biochemistry and siRNA. Melanosomes are cell type-specific membrane-bound organelles within ocular pigment epithelial cells and ocular and epidermal melanocytes in which melanin pigments are synthesized and stored. They are considered “lysosome-related organelles” that have unique morphological and functional features. Among lysosome-related organelles, melanosomes are part of a subclass that coexists with bona fide late endosomes and lysosomes. Over the past years we have addressed the cellular and molecular mechanisms regulating the formation of melanosomes in epidermal melanocytes. Through a fruitful combination of light and electron microscopy, molecular biology and biochemistry, our studies have provided a conceptual framework to decipher novel trafficking pathways that underlie melanosome formation and to understand how different cellular machineries cooperate to control these pathways. Our studies have shed light on the complexity of the endosomal system of melanocytes, the pathogenesis of Hermansky-Pudlak Syndrome (HPS) and related disorders of lysosome-related organelles, the formation of amyloid fibrils in neurodegenerative diseases, and alterations of intracellular trafficking that occur during progression to melanoma. We anticipate that new insights will contribute to the development of novel therapeutic strategies for pigment and neurodegenerative diseases and melanoma.