The Kallapur laboratory in the Division of Perinatal Biology is focused on understanding the pathogenesis and mechanisms of fetal inflammatory responses after exposure to chorioamnionitis. Virtually nothing is known about the immune responses of the preterm fetus. Using preterm sheep models, we recently demonstrated that lung monocytes mature to macrophage after exposure to chorioamnionitis and that IL-1 is an important mediator of chorioamnionitis induced fetal inflammatory responses. These observations help us understand how the preterm human fetus copes with chorioamnionitis. These studies are important because, up to 70% of the preterm infants born before 30 weeks gestation are exposed to chorioamnionitis. Epidemiological studies have shown that chorioamnionitis increases the risk of the preterm infant for developing White matter Brain disease, Necrotizing colitis and Bronchopulmonary dysplasia. The ultimate goal of this research is to find mechanisms of lung disease and fetal systemic inflammation in newborn infants using animal models and to find better therapeutic modalities for premature newborn infants.
The Kallapur lab works closely with Alan Jobe, MD, PhD, and Noah Hillman, MD, at Cincinnati Children’s Hospital Medical Center. In addition, we collaborate actively with international colleagues in Australia and the Netherlands. Our main animal model is sheep but we also use mice and rats for some experiments. Human studies are planned to start in 2009. The work is mainly funded by the NIH.
The main ongoing projects are:
- Mechanism of Fetal Systemic Inflammation, Immune Modulation and Organ Injury resulting from exposure to Chorioamnionitis – We are focusing on the role of IL-1 signaling but also study the role of other cytokines and chemokines. The animal model is sheep and the animal component of the experiment is done in collaboration with Drs. Newnham and Pillow in Perth, Australia and Dr. Kramer in Maastricht, Netherlands. We have two sheep models: Intraamniotic LPS injection and Intraamniotic Injection of Live Ureaplasma species. Translational human studies are planned to start in late 2009.
- Role of GM-CSF in the trafficking of inflammatory cells in the perinatal lung – This project uses transgenic mice: over-expressing GM-CSF in the lung epithelium and GM-CSF knock-out. The primary collaborator is Prof Bruce Trapnell, Cincinnati Children’s Hospital. In addition other mouse models of perinatal inflammation to study the interaction with post-natal inflammatory stimuli are planned.
Contact Dr. Kallapur
Suhas G. Kallpur, MD
Division of Pulmonary Biology
Cincinnati Children's Hospital Medical Center
3333 Burnet Ave. | Cincinnati, OH 45229-3039
suhas.kallapur@cchmc.org
phone (513) 636-3879
