The studies on the biology of normal and malignant pigment cells are to determine the mechanisms by which normal melanocytes are stimulated to proliferate and are transformed into melanoma cells; to devise ways of detecting malignant melanocytes with certainty and to be able to control their growth; to prevent skin cancers in albinos by providing the basis for correcting the genetic defect. The projects are grouped as follows: 1. Identifying the genes that control the proliferation and pigmentation of normal and malignant human melanocytes. Included are the gene for tyrosinase and bFGF and the gene for the MSH receptor. cDNA cloning, DNA transfection and antibodies will be used as tools to reach this goal. 2. Determining the subcellular localization of receptors and of other proteins related to proliferation and malignant transformation by the use of labeled ligands and/or antibodies. The approaches will include immunocytochemistry at light and electron miscroscopic levels, and cell fractionation. 3. Cytogenetic analyses of melanocytes from ordinary nevi, dysplastic and congenital nevi, primary melanomas and metastatic melanomas in order to identify chromosomal aberrations that occur in a nonrandom fashion. These analyses include morphological studies of chromosomes and molecular studies of changes in the sites of informative restriction fragment length polymorphisms (RFLPs). 4. Comparing the frequency of transformation of melanocytes from vitiligo skin and normal skin in vivo and in vitro. Studies in vitro will include both human and murine melanocytes, treated with UVB light, X-rays, chemical carcinogens. 5. Identifying cytokines in normal and malignant melanocytes. 6. Correcting the gene defect in human albino melanocytes. The expression of the transfected tyrosinase gene or tyrosinase-controlling gene sequences or respective cDNAs, derived from cultured normal human melanocytes, will be studied.
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