Our research is focused on the study of the ontogeny and control of heme catabolism and bilirubin production in the developing neonate. A better understanding of the role of increased bilirubin production in neonatal jaundice and the prevention of hemolytic jaundice has remained an overall objective of our program. To this end, we are actively investigating a more targeted, preventive approach to the diagnosis and treatment of newborns, who are high producers of the pigment and/or unable to efficiently eliminate bilirubin, thus leading to an accumulation of the pigment in circulation and tissues, which may lead to irreversible neurologic injury. Control of bilirubin production is a logical strategy, but has unexplored consequences for the immature mammal. Thus, we are studying the pivotal role of heme oxygenase (HO), the rate-limiting enzyme in the production of bilirubin, under a variety of commonly encountered pathological conditions, such as infection and hypoxia-ischemia, as well as in anti-oxidant defense, immune response and the regulation of hematopoiesis. In support of the above interests, studies are in progress, which are designed to screen a variety of metalloporphyrins and other compounds for maximum in vitro and in vivo efficacy with minimal side effects; to determine the ontogeny of the HO enzyme system in various murine tissues, focusing on perturbations resulting from treatment with HO inhibitors; and further to develop and test new technologies for noninvasive or minimally-invasive measurements of in vivo metabolism that could be used for diagnostic and monitoring purposes. We also study the causes of preterm birth and ways to prevent it.