Professor Joseph L. Napoli

Department of Nutritional Sciences and Toxicology

The goals of Dr. Napoli's laboratory are to understand, at the molecular level, endocrine and dietary regulation of retinoic acid (RA) homeostasis during development, disease and aging. Metabolism of retinol (vitamin A) produces the endocrine factor retinoic acid (RA). RA controls the differentiation programs of epithelial cells in the nervous system, the digestive tract, the immune system, and in skin and bone. RA also promotes growth, reproduction (fertility, placental development, embryonic development), and resistance to and recovery from infection. The embryo requires RA soon after conception and the requirement continues throughout the lifespan of vertebrates. Synthetic analogs of RA cause remission of skin diseases (such as severe cystic acne, psoriasis, and photoaging), augment treatment of diabetes, and function as cancer chemopreventive agents. RA acts by controlling gene transcription through transcription factors in the superfamily of nuclear hormone receptors. The dynamic and interrelated spatial-temporal expression of RA receptors, retinol (vitamin A)-binding proteins, RA-specific binding proteins, and enzymes of RA homeostasis constitute a unique endocrine system, obligatory for all vertebrate life.

Dr. Napoli's laboratory has ongoing projects directed to understanding metabolic control mechanisms of RA homeostasis and their impact on vitamin A function in mammals. Projects rely on techniques of molecular biology (genomic and cDNA cloning, polymerase chain reaction, analyses of mRNA expression), genetic manipulation (knock-out and transgenic mice), protein chemistry (heterologous expression and purification, protein-protein interaction), enzyme kinetics, and bioimaging (in situ hybridization, immunocytochemistry). Targeted areas include the nervous system, especially related to memory formation and diseases such as Alzheimer's and schizophrenia (hippocampus), the testis during spermatogenesis, embryonic development, and in adult mammary gland. Interactions between androgens and retinoids also are investigated.