Robert D. Wells, Ph.D.
1964, University of Pittsburgh School of Medicine
Texas A&M University System Health Sciences Center
Institute of Biosciences and Technology
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Robert D. Wells, Ph.D. 1964, University of Pittsburgh School of Medicine Texas A&M University System Health Sciences Center |
Research Interests: Repeating triplet sequences in hereditary neurological disease; DNA structural studies; gene expression
The goal of this laboratory is to elucidate the role of DNA structure in human genetic disorders. At least fifteen hereditary neurological diseases involve mutant trinucleotide repeats (CCG, CTG, and GAA). These include fragile X syndrome, myotonic dystrophy, Friedreich’s ataxia, and Huntington’s disease. The number of triplet repeats increases dramatically from normal individuals to carriers to afflicted individuals. This increase in copy number of the unstable sequences in subsequent generations accounts for the non-Mendelian genetic property termed anticipation. We have investigated non-B DNA for many years. The repeating triplet sequences adopt unusual DNA structures (flexible and writhed conformations, sticky DNA, triplexes) which are different from orthodox right-handed B-conformations. Our goal is to understand these structures and their role in human diseases.
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Genetic Instabilities and Neurological Diseases, Second Edition ( Robert D. Wells and Tetsuo Ashizawa, eds.), Elsevier-Academic Press Inc. (2006).
DNA Sequence-Specific Polyamides Alleviate Transcription Inhibition Associated with Long GAA•TTC Repeats in Friedreich’s Ataxia. Ryan Burnett, Christian Melander, James W. Puckett, Leslie S. Son, Robert D. Wells, Peter B. Dervan, and Joel M. Gottesfeld. Proc. Natl. Acad. Sci. USA 103, 11497-11502 (2006).
The Involvement of Non-B DNA Structures in Gross Chromosomal Rearrangements. (2006) Albino Bacolla, Marzena Wojciechowska, Beata Kosmider, Jacquelynn E. Larson, and Robert D. Wells. Invited Review for Special Issue of the Journal, DNA Repair. Dr. Michael Lieber, Editor, Elsevier Press 5, 1161-1170.
Double-Strand Breaks in the Myotonic Dystrophy Type 1 and the Fragile X Syndrome Triplet Repeat Sequences Induce Different Types of Mutations in DNA Flanking Sequences in E. coli. Beata Kosmider and Robert D. Wells. Nucleic Acids Research 34, 5369-5382 (2006).
Sticky DNA: in vivo Formation in E. coli and in vitro Association of Two Long GAA•TTC Sequences Related to Friedreich’s Ataxia. Leslie S. Son, Albino Bacolla, and Robert D. Wells. J. Mol. Biol. 360, 267-284 (2006).
Non-B DNA Structures Formed by Long DNA Repeats of DM1, DM2, and FRDA Genes, Not the Sequences per se, Promote Mutagenesis in Flanking DNA. Marzena Wojciechowska, Marek Napierala, Jacquelynn E. Larson, and Robert D. Wells. J. Biol. Chem. 281, 24531-24543 (2006).
Long Homopurine•homopyrimidine Sequences are Characteristic of Genes Expressed in Brain and in the Pseudoautosomal Region. Albino Bacolla, Jack R. Collins, Bert Gold, Nadia Chuzhanova, Ming Yi, Robert M. Stephens, Stefan Stefanov, Adam Olsh, John P. Jakupciak, Michael Dean, Richard A. Lempicki, David N. Cooper, and Robert D. Wells. Nucleic Acids Res. 34, 2663-2675 (2006).
Advancements in the Pathophysiology of Friedreich’s Ataxia and New Prospects for Treatments. Ngolela E. Babady, Nadege Carrelle, Robert D. Wells, Tracy A. Rouaualt, Michio Hirano, David R. Lynch, Martin B. Delatycki, Robert B. Wilson, Grazia Isaya; and Helene Puccio. Molecular Genetics and Metabolism 92, 23-35 (2007).
Program Affiliation:
Program in Human and Molecular Genetics