Our Team

Jennifer Wambach, MD is a clinically active neonatologist and has a longstanding interest in understanding the genetic causes of birth defects and extreme phenotypes in infants and children. Her research goals are (1) to use genomic sequencing technologies to identify the etiologies of birth defects and extreme phenotypes among infants and children and (2) to use functional studies to determine the disease mechanisms underlying these rare diseases. Specifically, this research laboratory focuses on the identification and functional characterization in cell-based systems for genetic disorders of surfactant metabolism which cause severe neonatal respiratory failure in term infants and childhood interstitial lung disease (chILD) in infants and children.

Research interests include genetic regulation of neonatal pulmonary surfactant deficiency has been suggested by studies of gender, genetic linkage, recurrent familial cases, targeted gene ablation in murine lineages, and by racial disparity in risk of neonatal respiratory distress syndrome. Successful fetal-neonatal pulmonary transition requires production of the pulmonary surfactant, a phospholipid-protein film that lines alveoli and maintains alveolar patency at end expiration. Our goal is to understand the genetic mechanisms that disrupt pulmonary surfactant metabolism and cause neonatal respiratory distress syndrome.

Daniel Wegner is involved in exome and genome sequencing analysis of babies with rare, extreme Mendelian phenotypes, both through the Washington University Undiagnosed Diseases Network (UDN) Clinical Site, as well as other Washington University genetics efforts. He also manages the research and bioinformatics efforts of the UDN clinical site. He is also involved in studying a specific ABCA3 mutation, c.3863-98C>T, and testing strategies for pharmacologic correction of this mutation in cell culture models.

Ping Yang is using a custom landing pad cell system to generate lung cell lines that stably express either wild type ABCA3 or individual ABCA3 mutations. She uses these cells for determining disease mechanism of ABCA3 mutations and screening of small molecules for pharmacologic correction of ABCA3 mutation-encoded disruption of lung function. Ping also assists with patient/family sample collection and storage for the UDN.

Ashton Hamilton utilizes the lab’s customized pulmonary epithelial cell lines that express individual ABCA3 variants to study disease mechanisms and investigate variant-specific activation of stress pathways, such as the unfolded protein response, ER-associated degradation pathways, and autophagy. She is also developing a pulmonary epithelial cell line to study a pathogenic, deep intronic variant in ABCA3 identified among Colombian infants with lethal neonatal respiratory failure. Hamilton also works with the Undiagnosed Diseases Network (UDN) to process and store samples, including fibroblasts and peripheral blood mononuclear cells (PBMCs), from UDN participants and families affected by extremely rare diseases.

Nora Doughty is analyzing UDN RNAseq data to identify gene expression differences, such as alternative splicing, allele-specific expression, or over-/under-expression, to uncover causative variants linked to participant phenotypes. She will also conduct genomic analyses to identify candidate variants associated with rare disease phenotypes in individual UDN participants.

Ansley Lee is currently involved in a project to assess EIF2S3 gene expression levels and RNA stability for a UDN participant with a rare neurologic phenotype. She utilized Taqman gene expression and Click-IT reporter assays. She has also worked on solving other UDN cases, using PCR and Sanger sequencing to perform candidate gene variant confirmation and familial variant segregation. She also assists in extracting DNA from blood and saliva samples collected from UDN participants for further genomic analyses.

Claire Min is currently working on a project to fully catalogue and classify all reported variants in the ABCA3 gene from our research studies, clinical databases and the medical literature. She recently worked on a project to sequence the ABCA3 gene for infants with lethal respiratory failure and suspected ABCA3 deficiency. She used PCR and Sanger sequencing to successfully identify ABCA3 variants for these infants.