David M Bedwell
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Explore the profile of David M Bedwell including associated specialties, affiliations and a list of published articles.
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49
Citations
2009
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Recent Articles
1.
Mangkalaphiban K, Fu L, Du M, Thrasher K, Keeling K, Bedwell D, et al.
Nat Commun
. 2024 Mar;
15(1):2486.
PMID: 38509072
Protein synthesis terminates when a stop codon enters the ribosome's A-site. Although termination is efficient, stop codon readthrough can occur when a near-cognate tRNA outcompetes release factors during decoding. Seeking...
2.
Li C, Liu Z, Anderson J, Liu Z, Tang L, Li Y, et al.
PLoS One
. 2023 Nov;
18(11):e0295009.
PMID: 38019847
A major unmet need in the cystic fibrosis (CF) therapeutic landscape is the lack of effective treatments for nonsense CFTR mutations, which affect approximately 10% of CF patients. Correction of...
3.
Chen J, Thrasher K, Fu L, Wang W, Aghamohammadzadeh S, Wen H, et al.
Am J Physiol Lung Cell Mol Physiol
. 2023 Apr;
324(6):L756-L770.
PMID: 37014818
Ten percent of cystic fibrosis (CF) patients carry a premature termination codon (PTC); no mutation-specific therapies exist for these individuals. ELX-02, a synthetic aminoglycoside, suppresses translation termination at PTCs (i.e.,...
4.
Siddiqui A, Dundar H, Sharma J, Kaczmarczyk A, Echols J, Dai Y, et al.
Int J Mol Sci
. 2023 Mar;
24(5).
PMID: 36901952
Mucopolysaccharidosis I-Hurler (MPS I-H) is caused by the loss of α-L-iduronidase, a lysosomal enzyme that degrades glycosaminoglycans. Current therapies cannot treat many MPS I-H manifestations. In this study, triamterene, an...
5.
Long A, Liu H, Liu J, Daniel M, Bedwell D, Korf B, et al.
Hum Mutat
. 2021 Oct;
43(1):30-41.
PMID: 34694046
We have created a panel of 29 NF1 variant complementary DNAs (cDNAs) representing missense variants, many with clinically relevant phenotypes, in-frame deletions, splice variants, and nonsense variants. We have determined...
6.
A small molecule that induces translational readthrough of CFTR nonsense mutations by eRF1 depletion
Sharma J, Du M, Wong E, Mutyam V, Li Y, Chen J, et al.
Nat Commun
. 2021 Jul;
12(1):4358.
PMID: 34272367
Premature termination codons (PTCs) prevent translation of a full-length protein and trigger nonsense-mediated mRNA decay (NMD). Nonsense suppression (also termed readthrough) therapy restores protein function by selectively suppressing translation termination...
7.
Leier A, Bedwell D, Chen A, Dickson G, Keeling K, Kesterson R, et al.
Mol Ther Nucleic Acids
. 2020 May;
20:739-753.
PMID: 32408052
Significant advances in biotechnology have led to the development of a number of different mutation-directed therapies. Some of these techniques have matured to a level that has allowed testing in...
8.
Keeling K, Bedwell D
Elife
. 2020 Mar;
9.
PMID: 32202493
Ribosomal profiling has shed new light on how ribosomes can ignore stop codons in messenger RNA.
9.
Xue X, Mutyam V, Thakerar A, Mobley J, Bridges R, Rowe S, et al.
Hum Mol Genet
. 2017 Jun;
26(16):3116-3129.
PMID: 28575328
In-frame premature termination codons (PTCs) account for ∼11% of all disease-associated mutations. PTC suppression therapy utilizes small molecules that suppress translation termination at a PTC to restore synthesis of a...
10.
Roy B, Friesen W, Tomizawa Y, Leszyk J, Zhuo J, Johnson B, et al.
Proc Natl Acad Sci U S A
. 2016 Oct;
113(44):12508-12513.
PMID: 27702906
A premature termination codon (PTC) in the ORF of an mRNA generally leads to production of a truncated polypeptide, accelerated degradation of the mRNA, and depression of overall mRNA expression....