William S. Blaner, PhD
Most of our recent work has employed genetic manipulations of mice to study these processes. One research project is focused on the essential biological processes that are mediated by retinol-binding protein (RBP), the sole serum transport protein for retinol. We have disrupted the gene for RBP in mice and demonstrated that these mice are a useful model to study retinoid-dependent actions, including ones in cancer prevention and normal embryologic development. The retinoid status of these mice is exceeding tenuous and consequently retinoid-dependent functions can be conveniently studied in this animal model. The laboratory is also studying the processes through which provitamin A carotenoids like β-carotene are converted to retinoids. Carotenoid conversion to retinoids is accomplished by the combined actions of three enzymes and several other intestinal proteins and we are studying how these different proteins interact and are regulated to ensure efficient conversion of carotenoids to retinoids. Another project in the laboratory explores the molecular basis for why 13-cis-retinoic acid (Accutane) is a more effective drug than all-trans-retinoic acid (Tretinoin) even though the latter retinoid is more active in regulating retinoid-responsive genes. Here we are seeking to establish actions for retinoids that are independent of their roles as transcriptional regulators. Finally the laboratory is developing new methodologies for assessing retinoid status in populations of infants that are at risk of vitamin A deficiency. This collaborative work that involves investigators in Brazil seeks to establish practical and cost-effective new methods for use assessing vitamin A status in field settings.
Retinoid (vitamin A and its metabolites) metabolism and actions.