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Faculty Detail    
Name DAVID M BEDWELL
Professor & Chairman, Dept of Biochemistry & Molecular Genetics; Associate Director, Cystic Fibrosis Research Center		  
Campus Address BBRB 432A Zip 2170
Phone  (205) 934-6593
E-mail  dbedwell@uab.edu
Other websites PubMed Listing
LinkedIn Profile
ResearchGate Profile
Google Scholar Profile
     

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  Biochemistry & Molecular Genetics  Biochemistry & Molecular Genetics Professor
Secondary  Cell, Developmntl, & Integrative Biology  Cell, Developmntl, & Integrative Biology Professor
Secondary  Genetics Chair Office  Genetics Chair Office Professor
Secondary  Microbiology  Microbiology Professor
Center  Center for AIDS Research  Center for AIDS Research Professor
Center  Comp Arthritis, MSK, Bone & Autoimmunity Ctr  Comp Arthritis, MSK, Bone & Autoimmunity Ctr Professor
Center  Comprehensive Cancer Center  Comprehensive Cancer Center Professor
Center  Ctr for Clinical & Translational Sci  Ctr for Clinical & Translational Sci Professor
Center  Cystic Fibrosis Research Center  Cystic Fibrosis Research Center Professor
Center  GL Ctr for Craniofacial, Oral, & Dental Disorders  GL Ctr for Craniofacial, Oral, & Dental Disorders Professor

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

Biographical Sketch 
David Bedwell (b. 1956), Professor and Chairman of the Department of Biochemistry and Molecular Genetics, completed his undergraduate studies in Microbiology at Purdue University (B.S. with Honors, 1979). His graduate work in Molecular Biology was done with Dr. Masayasu Nomura at the University of Wisconsin-Madison, (Ph.D., 1985). He then carried out a postdoctoral fellowship in Dr. Scott Emr's laboratory at Caltech. Dr. Bedwell joined the faculty at UAB in 1988. At the national level, he is in a second 5 year term on the Editorial Board of the Journal of Biological Chemistry, and has served as chair of both the Molecular Genetics B (MGB) and Molecular Genetics C (MGC) Study Sections of the National Institutes of Health. He has reviewed manuscripts for >60 scientific journals (including Science, Nature, and Cell). He was elected Fellow of the American Academy of Microbiology in 2011. At the institutional level, he has served as chair of the UAB School of Medicine Faculty Council (2016) and also currently serves as the Co-Director of the UAB structural Biology Program. He previously served 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
Xue, X., Mutyam, V., Thakerar, A., Mobley, J., Bridges, R.J., Rowe, S.M., Keeling, K.M. and Bedwell, D.M. (2017) Identification of the Amino Acids Inserted During Suppression of CFTR Nonsense Mutations and Their Functional Consequences. Human Molecular Genetics, EPub ahead of print.
 		 28575328 
B. Roy, W. Friesen, Y. Tomizawa, J. D. Leszyk, X. Xue, V. Mutyam, J. Mobley, S. M. Rowe, E. M. Welch, D. M. Bedwell, and A. Jacobson (2016) Ataluren stimulates ribosomal selection of near-cognate tRNAs to promote nonsense suppression. Proc. Nat. Acad. Sci. USA 113:12508-12513.  27702906 
K. Li, A.N. Turner, M. Chen, S. Brosius, T. R. Schobe, L. M. Messiaen, D. M. Bedwell, K. R. Zinn, C. Anastasaki, D. H. Gutmann, B. R. Korf, and R. A. Kesterson. (2016) Mice with missense and nonsense NF1 mutations display divergent phenotypes compared to NF1 patients. Disease Models & Mech. 9: 759-67.  27482814 
V. Mutyam, M. Du, X. Xue, E. L. White, R. Bostwick, L. Rasmussen, B. Liu, M. Mazur, J. S. Hong, E. Falk Libby, F. Liang, H. Shang, M. Mense, M. J. Suto, D. M. Bedwell, S. M. Rowe. (2016) Discovery of clinically approved agents that promote nonsense suppression. American Journal of Respiratory and Critical Care Medicine (AJRCCM) 194:1092-1103.  27104944 
Kelly, S. and Bedwell, D. (2015) Both Autophagy and Proteasomal Pathways Facilitate Ubp3p-Dependent Degradation of Translation and RNA Turnover Factors During Nitrogen Starvation in S. cerevisiae. RNA 21:898-910.  25795416 
Keeling, K., Xue, X., Gunn, G., and Bedwell D. (2014) Therapeutics Based on Stop Codon Readthrough. Ann. Rev. of Genomics and Human Genetics 15:371-94.  24773318 
Tuggle, K., Birket, S., Cui, X., Hong, J., Warren, J., Reid, L., Chambers, A., Ji, D., Gamber, K., Chu, K., Tearney, G., Tang, L., Fortenberry, J., Du, M., Cadillac, J., Bedwell, D., Rowe, S., Sorscher, E., and Fanucchi M. (2014) Characterization of Defects in Ion Transport and Tissue Development in Cystic Fibrosis Transmembrane Conductance Regulator (CFTR)-Knockout Rats. PLoS One 10: e.0091253  24608905 
Gunn, G., Dai, Y., Du, M., Belakhov, V., Kandeasamy, J., Schoeb, T., Baasov, T., Bedwell, D. and Keeling, K. (2014) Long-Term Nonsense Suppression Therapy Moderates MPS I-H Disease. Molecular Genetics and Metabolism 111: 374-381.  24411223 
Xue, X., Mutyam, V., Tang, L., Biswas, S., Du, M., Jackson, L., Dai, Y., Belakhov, V., Shalev, M., Chen, F., Schacht, J., Bridges, R., Baasov, T., Hong, J., Bedwell, D. and Rowe, S. (2014) Synthetic Aminoglycosides Efficiently Suppress CFTR Nonsense Mutations and are Enhanced by Ivacaftor. Am J Respiratory Cell & Molecular Biology 50: 805-816.  24251786 
Zhang S, Ranganath N, Skinner D, Bedwell D, Buckley-Lanier J, Sorscher E, Woodworth B. (2013) Marked repression of CFTR mRNA in the transgenic Cftr(tm1kth) mouse model. J Cyst Fibrosis 13: 351-352.  24378376 
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 208: 780-789.  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. 47:444-63.   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