Clinical Studies

Currently Liza Konnikova, MD, PhD, FAAP and her team are conducting patient-oriented research investigations that are focused on: 1) Understanding causes of necrotizing enterocolitis (NEC) and 2) Understanding causes of premature delivery.

Identifying Infants At High Risk For NEC

NEC is the leading cause of death in preterm infants. Despite advances in neonatal care, the survival of infants with NEC remains low – less than 50 percent in many cases. In part, this is due to our inability to predict which infants are at risk for the development of NEC and the subsequent failure to utilize preventative strategies.

The Konnikova Lab has identified that signaling via the innate immune receptor, Toll-like receptor 4 (TLR4) plays a key role in the development of NEC. We now seek to identify novel biomarkers for NEC in a longitudinal cohort study of infants with NEC, who are born at a major neonatal center, by assessing the TLR4 signaling capacity of these neonates using combined in vitro and in silico approaches. In so doing, we hope to advance the field by identifying newborns that are at risk for NEC development, thus creating a window for early prophylactic and interventional therapies.

Immunophenotyping of Placenta Specimens and Cord Blood

Every year more than 500,000 infants are born prematurely (prior to 37-weeks' gestation) in the United States, which is equivalent to one in every eight babies being born prematurely. Preterm birth (PTB) has been correlated with greater risk for many conditions that require an infant to spend time in Neonatal Intensive Care Units (NICU). However, the underlying causes of PTB have not been completely elucidated.

A link between preterm birth and placental inflammation has been reported in both infection-driven and non-infection-driven cases of PTB, but the specific cell types and signaling pathways involved remain unclear. Infants born preterm are at greater risk for multiple complications including sepsis, particularly in the first few days of life which can lead to severe neurodevelopmental complications or death in afflicted infants. Evidence suggests immune dysregulation may contribute to both the onset of PTB and increased risk of sepsis.

The role of the placenta in immune regulation and its impact on the outcomes of the neonate has not been fully explored. This has in part been difficult due to the large repertoire of cells and signaling molecules related to immune homeostasis that need to be investigated. To address this issue, our study utilizes the placenta and cord blood samples collected through the Magee Obstetric Maternal & Infant (MOMI) Biobank and processes them using mass cytometry (CyTOF) to simultaneously analyze 40 antibody cell surface and signaling markers at single cell resolutions to comprehensively evaluate cell populations. CyTOF also has the potential to aid in uncovering inflammatory signaling cascades by segregating cell types based on intracellular phosphorylated proteins and stimulated cytokine concentrations. In the current study we aim to systematically characterize the immune profile of the placenta and cord blood. We will then take the immune profile and correlate it to the clinical presentation of the mother and the clinical outcomes of the neonate.