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Faculty Detail     Name DAVID M BEDWELL Professor of Microbiology, Genetics and Cell Biology   Campus Address BBRB 432A Zip 2170 Phone 205-934-6593 E-mail dbedwell@uab.edu Other websites Lab Page PubMed Listing

Faculty Appointment(s) Appointment Type Department Division Rank Primary  Microbiology  Microbiology Professor Secondary  Cell, Developmntl, & Integrative Biology  Cell, Developmntl, & Integrative Biology Professor Secondary  Genetics   Genetics Chair Office Professor Center  Arthritis & Musculoskeletal Diseases Center  Arthritis & Musculoskeletal Diseases Center Professor Center  Center for AIDS Research  Center for AIDS Research Professor Center  Comprehensive Cancer Center  Comprehensive Cancer Center Professor Center  Cystic Fibrosis Research Center  Cystic Fibrosis Research Center Professor

Graduate Biomedical Sciences Affiliations Cell, Molecular, & Developmental Biology  Genetics and Genomic Sciences  Microbiology

Biographical Sketch  David Bedwell (b. 1956), Professor of Microbiology, completed his undergraduate studies in Microbiology at Purdue University (B.S. with Honors, 1979). His graduate work was done with Dr. Masayasu Nomura at the University of Wisconsin-Madison, (Ph.D., 1985) and a postdoctoral fellowship was carried out in Dr. Scott Emr's laboratory at Caltech. Dr. Bedwell joined the faculty at UAB in 1988. At the national level, he currently serves as a standing member and chair of the Molecular Genetics B (MGB) Study Section for the Center for Scientific Review at the National Institutes of Health. His outside interests include his family and sports.

Society Memberships Organization Name Position Held Org Link American Association for the Advancement of Science  member  http://www.aaas.org  American Society for Biochemistry and Molecular Biology  member  http://www.asbmb.org  American Society for Cell Biology  member  http://www.ascb.org  American Society for Microbiology  member  http://www.asm.org  American Society of Human Genetics  member  http://www.ashg.org  Genetics Society of America  member  http://www.genetics-gsa.org  The RNA Society  member  http://www.rnasociety.org

Research/Clinical Interest Title translation termination, post-transcriptional regulation, genetic diseases, cystic fibrosis, Hurler syndrome Description A major objective of research in Dr. Bedwell’s lab is to understand the mechanistic details of translation termination in eukaryotes. In addition, we are interested in Nonsense-Mediated mRNA Decay (NMD), which is a cellular mechanism that regulates mRNA abundance based on the presence of nonsense mutations. We are using a combination of genetics, biochemistry, and cell biology in a yeast and mammalian experimental systems to better understand the molecular details of how these processes are carried out. We are also investigating whether pharmacological agents can be used to suppress nonsense mutations that cause genetic diseases. First, we are exploring whether this novel therapeutic approach can benefit patients with cystic fibrosis (CF). CF is caused by mutations in the CFTR gene (which corresponds to the mouse Cftr gene). We have published several papers demonstrating that drugs can suppress nonsense mutations in the CFTR gene in various CF experimental systems, including cultured CF cell lines and a CF mouse expressing a human CFTR-G542X transgene. Most recently, we have constructed a new Cftr-G542X knock-in mouse model to explore this approach in a more physiologically relevant context. We are also investigating whether this therapeutic approach can benefit patients with the lysosomal storage disease mucopolysaccharidosis type I-H (MPS I-H, or Hurler syndrome). MPS I-H is caused by mutations in the human IDUA gene (which corresponds to the mouse Idua gene). We have constructed a Idua-W402X knock-in mouse and have evidence that nonsense suppression can partially alleviate the primary biochemical defect that causes this devastating genetic disease. Finally, the availability of these knock-in mouse models for CF and MPS I-H will allow us to explore whether the suppression of Nonsense-Mediated mRNA Decay (NMD) can further enhance the therapeutic effect provided by nonsense suppression agents. It is hoped that either nonsense suppression alone or in combination with NMD suppression will ultimately provide a therapeutic benefit for a broad range of human genetic diseases caused by nonsense mutations.

Selected Publications  Publication PUBMEDID Keeling KM, Wang D, Conard SE, Bedwell DM. (2012) Suppression of premature termination codons as a therapeutic approach. Crit Rev Biochem Mol Biol. 47(5):444-63.   22672057  Conard SE, Buckley J, Dang M, Bedwell GJ, Carter RL, Khass M, Bedwell DM. (2012) Identification of eRF1 residues that play critical and complementary roles in stop codon recognition. RNA 18:1210-21.   22543865  Wang, D., Belakhov, V., Kandasamy, J., Baasov, T., Li, S.-C., Li, T.-Y., Bedwell, D. and Keeling, K. (2011) The Synthetic Aminoglycoside NB84 Significantly Attenuates Biochemical Defects Associated with MPS I-H in the Idua-W392X Mouse. Mol. Genet. & Metabolism 105:116-25.  22056610  Keeling, K. and Bedwell D. (2011) Suppression of Nonsense Mutations as a Therapeutic Approach to Treat Genetic Diseases. Wiley Interdisciplinary Reviews RNA 2:837-852.  21976286  Rowe, S., Tang, L., Backer, K., Woodworth, B., Mazur, M., Buckley-Lanier, J., Nudelman, I., Belakhov, V., Schwiebert, E., Collawn, J., Bebok, Z., Baasov, T., Bedwell, D. (2011) Suppression of CFTR premature termination mutations and functional rescue of CFTR activity by synthetic aminoglycosides. J. Mol. Med. 89:1149-1161.  21779978  Lazrak, A., Jurkuvenaite, A., Chen, L., Keeling, K., Collawn, J., Bedwell, D. and Matalon, S. (2011) Enhancement of Alveolar Epithelial Sodium Channel Activity with Decreased Cystic Fibrosis Transmembrane Regulator Expression in Mouse Lung. Am. J. Physiol. - Lung Cell. Mol. Physiol. 301: L557-567.  21743028  Wang, D., Shukla, C., Liu, X., Schoeb, T., Clarke, L., Bedwell, D. and Keeling, KM. (2010) Characterization of an MPS I-H knock-in mouse that carries a nonsense mutation analogous to the human IDUA-W402X mutation. Mol. Genet. & Metabolism 99: 62-71 (highlighted on cover).   19751987  Vallabhaneni, H., Fan-Minogue, H., Bedwell, D, and Farabaugh, P. (2009) A connection between stop codon reassignment and frequent use of shifty stop frameshifting in Euplotes species. RNA 15: 889-897.  19329535  Du, M., Keeling, K. Fan, L., Liu, X., and Bedwell, D. (2009) Poly-L-Aspartic Acid Enhances and Prolongs Gentamicin-Mediated Suppression of the CFTR-G542X Mutation in a CF Mouse Model. J. Biol. Chem. 284: 6885-92.  19136563  Fan-Minogue, H., Du, M., Pisarev, A., Kallmeyer, A., Salas-Marco, J., Keeling, K., Thompson, S., Pestova, T. and Bedwell, D. (2008) Distinct eRF3 requirements suggest alternate eRF1 conformations mediate peptide release during eukaryotic translation termination. Mol. Cell 30: 599-609.  18538658  First Prev   1 2 3 of  3  Next Last

Keywords Translation Termination, Treatment of Genetic Diseases, Suppression of Nonsense Mutations

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