Professor and Chair
UAB School of Medicine
David M. Bedwell, PhD, is Professor & Chair of the Department of Biochemistry & Molecular Genetics in the Heersink School of Medicine at the University of Alabama at Birmingham (UAB). The Bedwell lab seeks to understand the mechanistic details of translation termination in eukaryotes, and to use that knowledge to develop therapeutic strategies for a range of genetic diseases caused by premature translation termination mutations (PTCs). In addition, other important cellular processes also intersect with the process of translation termination. For example, conserved cellular machineries also regulate the abundance of mRNAs based on the location of stop codons through the process of Nonsense-Mediated mRNA Decay (NMD). We are using a combination of genetics, biochemistry, and cell biology to better understand the molecular details of these processes.
In particular, we are applying our findings to the disease cystic fibrosis (CF). CF is caused by mutations in the CFTR gene. Roughly 10% of CF patients carry a premature stop mutation in the CFTR gene. We are working to identify small molecules that suppress premature stop mutations in the CFTR gene in cultured CF cells and knock-in CF mice carrying PTCs. We have also recently identified the range of amino acids inserted during the suppression of various CFTR stop codons in mammalian cells and are using that information to develop strategies to enhance the CFTR activity obtained by PTC suppression. Our ultimate goal is to develop small molecule(s) that restore enough CFTR expression and function to provide a therapeutic benefit to CF patients.