Inflammation induced preterm labor and fetal injuries are major unsolved problems in perinatal medicine. The Kallapur Laboratory in the Division of Perinatal Biology is focused on how inflammation at the maternal-fetal interface triggers preterm labor and causes fetal organ injury responses. These questions are important because about 11% of all births in the U.S. deliver preterm. A major cause of preterm delivery is chorioamnionitis, or inflammation at the maternal-fetal interface. Prematurity and chorioamnionitis are major causes of neonatal mortality and injury responses to fetal organs such as the lung, brain and the intestines. The ultimate goal of this research is to find novel targeted therapeutic modalities to prevent prematurity and its related complications.
We have developed powerful animal model systems (Sheep and Rhesus macaques) and human protocols to determine the mechanisms by which infection is associated with preterm birth in some pregnancies, but do not lead to preterm birth in others. Testing the intersection of intrauterine inflammation, maternal inflammation, microbial colonization we have found that chorioamnionitis, or inflammation of the fetal membranes, initiated by interleukin-1 beta drives inflammation of maternal uterine cells lining the fetal membranes by recruiting neutrophils which amplify the inflammatory starting signal by producing tumor necrosis factor alpha and interleukin-8, IL-1 signaling also mediates chorioamnionitis induced lung and gut injury in the fetus. New studies demonstrate a critical role for inflammatory signals that enhance neutrophil survival in generating inflammation, which rely on the increased expression of anti-apoptotic molecules.
The Kallapur Lab works closely with Alan Jobe, MD, PhD, and Claire Chougnet, PhD at Cincinnati Children’s Hospital Medical Center. In addition, we have a number of outside strong collaborations including Lisa Miller, PhD, at UC Davis (California National Primate Center), Dr. John Newnham (Perth, Australia) and Dr. Boris Kramer (Maastricht University, the Netherlands). The studies are funded by the NIH, March of Dimes and Burroughs Wellcome grants.