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Vincent J. Hearing, Ph.D.
Melanoma and Melanogenesis
This project is focused on characterizing parameters important to the growth, differentiation and function of normal melanocytes and their significance to the outgrowth and metastasis of transformed melanocytes (malignant melanoma). These studies have evolved into an identification of pigment-specific genes, i.e., genes that encode melanocyte-specific proteins, and determining their regulation and functions. These proteins have generally been found to be localized in melanosomes, specific organelles that serve as the site of melanin pigment deposition; they function as catalytic and/or structural entities but perhaps more importantly serve as specific targets of natural and induced host immune responses to melanoma growth.
These studies have identified, isolated and characterized several different melanogenic enzymes (including tyrosinase, TRP1, and TRP2) that regulate the quality and quantity of pigment produced within melanocytes, and thus influence normal melanocyte function, including its role in photoprotection. We have also characterized a melanosomal structural matrix protein (gp100/silver) that is important to the viability of melanocytes. Further, we have characterized several other proteins (MART1, P and MATP) that play important roles in the trafficking and function of melanosomal components. These melanogenic proteins are encoded within a family of pigmentation-related genes that are specifically expressed by mammalian melanocytes. Interestingly, although expression of these genes is restricted to pigment-producing tissues, we have shown that they can be independently regulated following stimulation or inhibition of differentiation. The phenotypic and functional properties of the melanins produced in melanosomes can differ dramatically, and effects on the functional and photoprotective properties of those melanins are currently being examined.
We are using proteomics and informatics approaches to identify novel constituents of melanosomes that might prove to be othe melanocyte-specific markers and that map to pigment-related loci. Of special interest is the fact that many (perhaps all) melanoma-specific antigens are normally expressed melanosomal proteins. We have initiated studies to identify novel antigens expressed by less differentiated melanoma cells that might serve as additional immune targets in heterogeneous tumor populations.
Finally, we continue to collaborate with the FDA Photosciences facility to examine the effects of UV on human skin of various phenotypes and to characterize the role(s) of melanin in photoprotection
This page was last updated on 4/9/2014.