Professor
University of California, Berkeley
J. Napoli has been studying vitamin A activation into retinoic acid (RA), and the physiological functions of RA over forty years. At a time when the presence of RA in tissues and its significance was questioned by some, he developed methods for quantifying RA, quantified RA in tissues, showed that arresting its degradation shifted its dose-response curve to the left (enhanced potency), and characterized its biosynthesis. He showed that Crbp and Crabp1 chaperone retinol and RA metabolism. He identified retinol dehydrogenases/reductases as belonging to the short-chain dehydrogenase/reductase gene family, cloned several, characterized their enzymology, and showed that alcohol dehydrogenases functioned only to generate vitamin A toxicity, during administration of excess retinol. Next, he identified, cloned and biochemically characterized Raldh1 and Raldh2. Recently, he has been studying the physiological functions of endogenous RA, by phenotyping Rdh1 and Rdh10 ablations. These KOs decrease RA tissue concentrations selectively and modestly. This cannot be done reproducibly by withdrawing vitamin A from diets of model animals, especially if they are fed chow diets. This work suggests that different Rdh serve different functions. Rdh1 ablation enhances adiposity and lowers body temperature by reducing lipolysis and mitochondria function in brown adipose. The heterozygous Rdh10 ablation results in male liver steatosis, male adiposity, female bone adipocyte formation, and male muscle impairment, with enhanced female muscle function. These data show a nexus among RA concentrations and action, and estrogen, insulin and cortisol. This lab's work also showed that neurons harbor extra-nuclear RARa in RNA granules, primed for rapid translation.