Although individually rare, Mendelian genetic disorders collectively constitute a significant burden of human disease.

Moreover, evidenced by the last century of biomedical research, these disorders represent exceptionally fruitful and tractable inroads into understanding molecular mechanisms shared among rare and common disease alike. We are currently most interested in identifying and mechanistically dissecting genetic disorders affecting the biogenesis, trafficking, and function of subcellular compartments (organelles) in specialized cells of the lungs. We aim to apply an understanding of such rare diseases both to uncover new cell biology and to develop novel therapeutic approaches which target fundamental, initiating steps in pulmonary diseases.

1. Genetic disorders of lysosome related organelle biogenesis cause pediatric interstitial lung disease. We are developing and applying new tools to probe why.
2. Germline variants in telomerase complex components cause familial pulmonary fibrosis. We are working to understand the molecular mechanisms.
3. Mutations in a lysosomal membrane protein causes fatal neonatal lung disease in dogs. We have generated new models to understand how.
4. We previously described the function of an orphan kinase, NEK10, in causing human airway disease. We are working to understand its regulation and targets.