The importance of skin pigmentation, particularly with respect to its implications for photoprotection against skin cancers (including malignant melanoma), has resulted in a dramatic surge in research on this topic. The alarming increase in incidence of skin cancers (especially melanoma) has been a major stimulus behind those efforts. Our laboratory continues to remain at the forefront of research on the regulation of mammalian pigmentation and focuses on characterizing: (1) pigment-related genes and their functions involved in melanocyte differentiation, (2) the biochemistry of melanins formed in the skin and their photoprotective properties, and (3) the biology of melanocyte specific differentiation antigens that serve as melanoma-specific targets. This research project is focused on characterizing parameters important to the growth, differentiation and function of normal melanocytes, and their significance to the growth and/or the metastasis of transformed melanocytes (malignant melanoma). These studies have evolved into an examination of the function and regulation of pigment-related genes, i.e. genes that encode melanocyte-specific proteins. Such 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 host immune responses to malignant melanoma. Our efforts in this regard have recently been targeted in 4 primary areas of interest, all of them dealing with structure, function and/or melanoma-targeting of melanosomal proteins.

Agency
National Institute of Health (NIH)
Institute
Division of Basic Sciences - NCI (NCI)
Type
Intramural Research (Z01)
Project #
1Z01BC009100-18
Application #
6950524
Study Section
(LCB)
Project Start
Project End
Budget Start
Budget End
Support Year
18
Fiscal Year
2003
Total Cost
Indirect Cost
Name
Basic Sciences
Department
Type
DUNS #
City
State
Country
United States
Zip Code
Watabe, Hidenori; Valencia, Julio C; Le Pape, Elodie et al. (2008) Involvement of dynein and spectrin with early melanosome transport and melanosomal protein trafficking. J Invest Dermatol 128:162-74
Wolber, Rainer; Schlenz, Kathrin; Wakamatsu, Kazumasa et al. (2008) Pigmentation effects of solar-simulated radiation as compared with UVA and UVB radiation. Pigment Cell Melanoma Res 21:487-91
Rouzaud, Francois; Costin, Gertrude-E; Yamaguchi, Yuji et al. (2006) Regulation of constitutive and UVR-induced skin pigmentation by melanocortin 1 receptor isoforms. FASEB J 20:1927-9
Valencia, Julio C; Watabe, Hidenori; Chi, An et al. (2006) Sorting of Pmel17 to melanosomes through the plasma membrane by AP1 and AP2: evidence for the polarized nature of melanocytes. J Cell Sci 119:1080-91
Chen, Kevin G; Valencia, Julio C; Lai, Barry et al. (2006) Melanosomal sequestration of cytotoxic drugs contributes to the intractability of malignant melanomas. Proc Natl Acad Sci U S A 103:9903-7
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Takahashi, Kaoruko; Hoashi, Toshihiko; Yamaguchi, Yuji et al. (2006) UV increases the nuclear localization of apurinic/apyrimidinic endonuclease/redox effector factor-1 in human skin. J Invest Dermatol 126:2723-6
Hoashi, Toshihiko; Muller, Jacqueline; Vieira, Wilfred D et al. (2006) The repeat domain of the melanosomal matrix protein PMEL17/GP100 is required for the formation of organellar fibers. J Biol Chem 281:21198-208
Rouzaud, F; Hearing, V J (2006) Analysis of the transcriptional regulation of melanocytic genes by alphaMSH using the cDNA microarray technique. Cell Mol Biol (Noisy-le-grand) 52:21-31
Ando, Hideya; Wen, Zhi-Ming; Kim, Hee-Yong et al. (2006) Intracellular composition of fatty acid affects the processing and function of tyrosinase through the ubiquitin-proteasome pathway. Biochem J 394:43-50

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