Washington University in St. Louis (WU)
I am interested in understanding the contribution of surfactant protein-C (SFTPC) to the risk of neonatal respiratory distress syndrome (RDS). SP-C mutations are known to cause interstitial lung disease in infants and children and are transmitted in an autosomal dominant fashion with variable penetrance. The lung disease resulting from mutations in SP-C results from aggregation of misfolded or misrouted proSP-C peptides that overwhelm the capacity of cellular quality control pathways and activate the unfolded protein response (UPR). The UPR refers to intracellular signaling pathways that decrease protein synthesis by decreasing RNA translation, increase degradation of accumulated proteins, and increase the protein folding and secretion capacity of the endoplasmic reticulum. My work thus far has been to 1) determine the prevalence of the most common SFTPC mutation; 2) determine if variants in the SP-C gene are overrepresented in newborns with RDS; and to 3) determine whether variants in SFTPC interact with variants in key genes of the UPR to increase the risk for neonatal RDS.