Antonia Popova, MD is an assistant professor of Pediatrics and Communicable Diseases in the Division of Pediatric Pulmonology.
Bronchopulmonary dysplasia (BPD) is a chronic lung disease of prematurely-born infants in which lung alveoli fail to form normally. Many prematurely born infants with BPD develop asthma later in life. We investigate the cellular and molecular innate immune mechanisms that are activated and primed by exposures associated with preterm birth (e.g. hyperoxia or infection) and contribute to BPD and asthma development. Our approach combines animal and in vitro experiments, and, in selected studies, human subjects research. Our goal is to uncover novel innate immune pathways responsible for long-term lung disease in prematurely born infants and identify new targets for therapeutic intervention. Current projects focus on:
- Effect of early life hyperoxic exposure on lung innate immune responses and the development of BPD and asthma. We are investigating the mechanisms by which early-life hyperoxic exposure primes the pulmonary innate immune system and leads to enhanced inflammatory responses to respiratory viral infections. Since hyperoxia induces lung cell necrosis, we focus on necrotic cells exposed F-actin, a damage-associated molecular pattern (DAMP) which through its binding to Clec9a, a DAMP receptor on lung CD103+ DCs induces their activation. We are exploring the mechanisms of this priming effect and its contribution to exaggerated pro-inflammatory responses to future TLR3 stimulation.
- Role of infection and inflammation on impaired lung alveolar growth. Since inflammation and infection, have been associated with BPD development, we have developed a novel mouse model of BPD by inoculating immature mice with LPS, administered in repeated doses intranasally. Chronic neonatal LPS exposure induces inflammation and disrupts alveolar growth leading to fewer and larger alveolar spaces, findings similar to human BPD. We are investigating the contribution of CCR2+ exudative macrophages in chronic neonatal LPS exposure-induced pulmonary inflammation and hypoalveolarization.