Research Areas

Sudden Unexpected Infant Death (SUID) is the leading cause of infant mortality up to one year of age and many of these are classified as Sudden Infant Death Syndrome (SIDS). SIDS is the sudden unexplained cause of death of an otherwise healthy baby less than 1 year of age. Unfortunately, due to the unknown cause of death, SIDS pathophysiology is complex and largely anecdotal. Using a novel model of SIDS, we are at the forefront of discovering potentially new pathophysiological features such as the role of the extracellular matrix in modulating the proposed central (brainstem) and peripheral (carotid body) abnormalities of respiratory and autonomic control. We are also actively engaged in studies aimed at identifying diagnostic tools and detection of predictive biomarkers for early identification of infants at risk of SIDS and developing potentially promising prophylactic treatment options that may help prevent such a devastating cause of infant death.

In our SIDS model, chronic hypoxia exposure during a critical period of development increases extracellular matrix expression (bottom) in the brainstem respiratory/autonomic nuclei (nTS, nucleus tractus solitarius; DMNV, dorsal motor nucleus of the vagus, AP, area postrema; XII, hypoglossal nucleus; CC central canal).

Around 7% of pregnant women admit to use of prescription opioids during pregnancy, which can lead to an infant being born with neonatal opioid withdrawal syndrome (NOWS). A baby is diagnosed with NOWS every 24 minutes in the US alone and exhibit signs of withdrawal ranging from irritability, vomiting, tremors, and seizures which can lead to death. Our focus in this area is motivated by the rising opioid epidemic and we are at the forefront of discovering mechanisms of withdraw in these infants, identifying biomarkers of withdrawal, and are also testing an adjunctive therapy to treat it.

Sepsis is a dysregulated host response to infection leading to life-threatening organ dysfunction affecting thousands of infants annually in the US. Using a model of neonatal sepsis, we are discovering the mechanisms of lethality to gram negative endotoxin is associated with respiratory control dysfunction, exaggerated autonomic responses, and thermoregulatory collapse. We are interested in understanding the ways that microglia, inflammation and the extracellular matrix contribute to the lethality of neonatal sepsis and are developing novel prophylactic interventions to prevent the thousands of infant deaths that occur from sepsis annually.

The MacFarlance Lab also developed the first neonatal mouse model of continuous positive airway pressure (CPAP). We use this to model CPAP administration to preterm infants to assess its effects on airway hyper-reactivity. Most studies focus on hyperoxia exposure to investigate its effects on airway hyper-reactivity. However, with this new technology to administer CPAP to a neonatal mouse without the use of anesthesia or major surgical preparation, we are beginning to open possibilities toward understanding how CPAP (independently of hyperoxia) modifies lung development. The focus of these studies are aimed at understanding the role of hyaluronan and other components of the ECM in lung development, and how they are affected by CPAP and hyperoxia. More recent studies have begun to explore the therapeutic potential of human mesenchymal stem cell therapy.