HO activity produces equimolar amounts of carbon monoxide (CO), iron, and biliverdin (which is immediately converted to bilirubin). In the ’70s, Dr. David Stevenson began studying HO-1 in relation to bilirubin production, where too much HO-1 leads to an increase in bilirubin and jaundice in the newborn. He and his team now look at the entire enzymatic pathway at different points of gestation, and how HO-1 production can be modulated to affect changes in vascular development or antioxidant defense. Teaming up with the Stevenson laboratory, Dr. Christopher Contag and members of his laboratory have been studying how HO-1, as a mediator of stress response, influences hematopoietic stem cell differentiation and/or division. It appears as if HO-1 is a key determinant of a stem cell’s choice to self-renew or differentiate upon division, making it a prime regulator of the developing hematopoietic and immune systems.
Changes in the production of heme oxygenase impact vascular development. Expression of HO-1 is especially important in the placenta during pregnancy, where low HO-1 levels might be a factor in pre-term birth (12 percent of all US births), preeclampsia (affecting about 5-8% of pregnant women) or spontaneous abortion. In a baby with hemolysis, or rapid breakdown of red blood cells, HO-1 activity is increased and may lead to an increase in bilirubin production. If bilirubin levels are too high, this can cause brain injury called kernicterus. Dr. Vinod Bhutani heads up the Global Prevention of Kernicterus Network, which is a prime example of our translational approach to research where the work we do in the lab interfaces with our clinical efforts.