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Richard M. Niles, Ph.D.
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Major
Research Interests
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Our
laboratory is investigating the mechanism by which vitamin A and its
physiological metabolites (retinoids) arrest growth and induce differentiation
of cancer cells. In these studies
we are currently using cDNA microarrays, containing 1200 different genes, to
examine changes in early gene expression (within 4 hrs.) in retinoid-treated
melanoma cells. We have identified
several novel retinoid-regulated genes.
A
second area of research involves determining the expression and function of
peroxisome proliferator activated receptors (PPAR) in mouse and human
melanocytes/melanoma. These nuclear
receptors regulate the expression of genes controlling lipid metabolism.
They also influence the growth and differentiation of cancer cells.
We have found that these receptors are expressed in melanocytes and
melanoma and that their activation inhibits melanoma growth and alters melanin
production. This project is a
collaboration between my laboratory and investigators at the University of
Cincinnati and Washington State University.
A
recent area of investigation involves the plant polyphenol/phytoestrogen,
resveratrol. This compound is found
in high concentrations in red wine and is thought to protect against the
development of cardiovascular disease. Several
reports indicate that it also has anti-tumor activity.
We have found that resveratrol is a potent inducer of apoptosis
(programmed cell death) in human melanoma cell cultures. We
are currently determining the ability of resveratrol to inhibit the growth of
melanoma tumors in mice and exploring the molecular mechanisms responsible for
the activity of resveratrol.
Representative
Publications
Niles,
R.M. Vitamin A and Cancer.
Nutrition 16: 573-576, 2000
Niles, R.M. The Use of Retinoids in the Prevention and Treatment of Skin Cancer. Expert Opin. Pharmacother. 3: 1-5, 2002.
Boskovic, G., and Niles, R.M. Regulation of RARa by Protein Kinase C in Mouse Melanoma Cells. J. Biol. Chem. 277: 26113-26119, 2002.
Huang, Y., and Niles, R.M. Inhibition of AP-1 Transcriptional Activity Attenuates Retinoic Acid-Induced Growth Arrest and Differentiation of Mouse Melanoma Cells. J. Cell. Physiol. 194: 162-170, 2002.
Niles, R.M. Vitamin A (Retinoids) Regulation of Mouse Melanoma Growth and Differentiation. J. Nutr. 133: 282-286, 2003.
Niles, R.M., McFarland, M., Weimer, M.B., Redkar, A., Fu, Y.-M., and Meadows, G.G. Resveratrol is a Potent Inducer of Apoptosis in Human Melanoma Cells. Cancer Letters 190: 157-163, 2003.
Recent Graduate Students and Postdoctoral Fellows