Martin K. and Jill F. Sneider Endowed Fellowship Award
Amjad Horani, M.D.
Center for Pediatric Pulmonary Disease
7/1/2013 - 6/30/2016
Motile cilia are components of the mucociliary escalator and respiratory tract host defense, which when dysfunctional cause primary ciliary dyskinesia (PCD), recurrent otitis media, congenital heart disease, and infertility. Despite the recent advances in genetics, many of the genes related to PCD are still unknown and the functions of newly reported proteins are still being elucidated.
To better evaluate the importance of assembly and preassembly proteins, we set forth to:
- Characterize the biochemical and functional features of mutations in HEATR2, including the L795P founder mutation.
- Identify the role of HEATR2 during normal ciliated airway epithelial cell differentiation.
This award allowed us to identify unique interactions between HEATR2 and other cilia preassembly proteins, including potential targets for therapy. The impact of specific human mutations on protein function was also identified, which can now be used to understand the disruption in normal cilia formation, and investigate tools to ameliorate the effects of these mutations on protein function.
Understanding the functions of newly identified proteins mutated in rare pediatric airway diseases is an important tool for understanding the biology of the airway cells and for advancing research aimed at identifying therapeutic targets in these conditions.