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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
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Education
Undergraduate  Purdue University    1980  Bachelor of Science (Honors) 
Graduate  University of Wisconsin-Madison    1985  Ph.D. in Molecular Biology 


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 on the Editorial Board of the Journal of Biological Chemistry, and is chair of the Molecular Genetics B (MGB) Study Section of the National Institutes of Health. He has reviewed manuscripts for >50 scientific journals (including Science, Nature, and Cell). He was elected Fellow of the American Academy of Microbiology in 2011.

At the institutional level, he previously served as Chair of the UAB Dept. of Microbiology Promotions Committee (2009-2012); as a member of the UAB SOM Faculty Council (2003-2007); and as Director the the UAB Cell and Molecular Biology (CMB) Graduate Program (1996-2002).

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 Control of Gene Regulation; Suppression of Nonsense Mutations to Treat Genetic Diseases
Description
Research in Dr. Bedwell’s lab studies the mechanistic details of translation termination and Nonsense-Mediated mRNA Decay (NMD), which is a cellular mechanism that regulates mRNA abundance based on the presence of nonsense mutations in eukaryotes. We are also investigating whether pharmacological agents can suppress nonsense mutations that cause genetic diseases. 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
Aeffner, F., Abdulrahman, B., Hickman-Davis, J., Amer, A., van Rooijen, N., Bedwell, D., Sorscher, E., & Davis, I. (2013) Heterozygosity for the F508del CFTR mutation imparts a survival advantage in influenza. J. Infectious Diseases, (Epub ahead of print).  23749967 
Keeling, K., Wang, D., Du, M., Dai, Y., Murugesan, S., Chenna, B., Clark, J.; Belakhov, V., Kandasamy, J., Velu, S., Baasov, T., and Bedwell, D. (2013) Attenuation of Nonsense-Mediated mRNA Decay Enhances In Vivo Nonsense Suppression. PLoS One 8: e60478 1-11.  23593225 
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 
Du, M., Liu, X., Welch, E., Peltz, S. and Bedwell, D. (2008) PTC124 is an orally bioavailable compound that promotes suppression of the human CFTR-G542X nonsense allele in a CF mouse model. Proc. Nat. Acad. Sci. USA 105: 2064-2069.  18272502 
Fan-Minogue, H and Bedwell, D. (2007) Eukaryotic ribosomal RNA determinants of aminoglycoside resistance and their role in translational fidelity. RNA 14: 148-157.  18003936 
Kallmeyer, A., Keeling, K. and Bedwell, D.M. (2006) Eukaryotic release factor 1 phosphorylation by CK2 protein kinase is dynamic but has little effect on the efficiency of translation termination in Saccharomyces cerevisiae. Eukaryot. Cell. 5:1378-87.   16896221 
Keeling, K., Salas-Marco, J., Osherovich, L. and Bedwell, D. (2006) Tpa1p is part of an mRNP complex that influences translation termination, mRNA deadenylation and mRNA turnover in Saccharomyces cerevisiae. Mol. Cell. Biol. 26: 5237-5248  16809762 
Du, M., Keeling, K., Fan, L., Liu, X., Kovaçs, T., Sorscher, E., and Bedwell, D. (2006) Clinical doses of amikacin correct the CFTR-G542X stop mutation more efficiently than gentamicin in a transgenic CF mouse model. J. Mol. Med. 84: 573-82.  16541275 
Kellermayer, R., Szigeti, R., Keeling, K., Bedekovics, T. and Bedwell, D. (2006) Aminoglycosides as potential pharmacogenetic agents in the treatment of Hailey-Hailey disease. J. Inv. Derm. 126: 229-231.  16417242 
Salas-Marco, J., Kallmeyer, A., Fan, H., Klobutcher, L., Farabaugh, P., and Bedwell, D. (2006) Distinct paths to stop codon reassignment in the ciliates Tetrahymena and Euplotes. Mol. Cell Biol. 26: 438-447.  16382136 
Salas-Marco, J. and Bedwell, D. (2005) Discrimination between defects in elongation fidelity and termination efficiency provide mechanistic insights into translational readthrough. J. Mol Biol 348: 801-815.  15843014 
Salas-Marco, J and Bedwell, D (2004) GTP hydrolysis by eRF3 facilitates stop codon decoding during eukaryotic translation termination. Mol. Cell. Biol. 24: 7769-7778.  15314182 
Keeling, K., Lanier, J., Du, M., Salas-Marco, J., Gao, L., Kaenjak-Angeletti, A., and Bedwell, D. (2004) Leaky termination at a premature stop codon antagonizes nonsense-mediated mRNA decay in S. cerevisiae. RNA 10: 691-703.  15037778 
Keeling, K., Du, M. and Bedwell, D. (2006) Therapies of Nonsense-Associated Diseases. In “Nonsense-Mediated mRNA Decay”, L.E. Maquat, Editor, Landes Bioscience. Pages 121-36.   
Keeling, K and Bedwell, D. (2005) Pharmacological suppression of premature stop mutations that cause genetic diseases. Current Pharmacogenomics 3: 259-269 (review).   

Keywords
Translation Termination, mRNA Turnover, Suppression of Nonsense Mutations to Treat Genetic Diseases