David L. Nelson, Ph.D.
Professor of Molecular and Human Genetics
Professor, Program in Integrative Molecular and Biomedical Sciences
B.A., University of Virginia, 1978
Ph.D., Massachusetts Institute of Technology, 1984
Postdoc, National Institute for Neurological, Communicative Disorders and Stroke, National Institutes of Health, 1985
Postdoc, Baylor College of Medicine, 1986
One of the most exciting recent developments in human genetics has been the identification of unstable trinucleotide repeats involved in high frequency mutations leading to more than one dozen genetic disorders, including myotonic dystrophy and Huntington's disease. With collaborators, Dr. Nelson described the first of these unstable DNA sequences, a CGG trinucleotide repeat in the FMR1 gene and responsible for the fragile X site and mental retardation found in people with Fragile X syndrome. This is the most common form of inherited mental retardation, with a frequency of ~1/2000 males in the general population. The mechanism by which this mutation leads to disease is through loss of function of the FMR1 gene product due to diminished expression resulting from aberrant methylation of the gene. Recent evidence suggests that the gene product of FMR1 interacts with complexes of RNA and ribosomes, implying a role in regulation of translation. Efforts in the Nelson group are focused on dissecting this pathway and understanding the development of DNA instability at this locus. Two additional fragile sites are found in the vicinity of the FMR1 gene on the X chromosome. The Nelson laboratory described one of these at the molecular level (FRAXF) and has identified a second gene involved in mental retardation expressed from the FRAXE fragile site (FMR2). Efforts to understand the function of FMR2 are underway.
The group has recently identified the gene defect in the X-linked disorder Incontinentia Pigmenti. This mutation is lethal in males, and leads to a spectrum of effects in females. Mutations are found in an essential modulator of NF-kB activity (NEMO), and the role of loss of function for this protein in the disease is under investigation.
The Nelson group has been involved in numerous aspects of the Human Genome Project, with key input into the mapping and sequencing of the human X chromosome, and participation in several other sequencing projects, from fly to Rhesus monkey. Dr. Nelson also has interest in the genetic contribution to common disorders such as cancer, and has investigated the potential role of common variants in genes involved in DNA repair in human disease.
- Nelson DL, Orr HT, Warren ST (2013). The unstable repeats – Three evolving faces of neurological disease. Neuron 77: 825-843. PubMed PMID: 23473314
- Lee J, Moulik M, Fang Z, Saha P, Zou F, Xu Y, Nelson DL, Ma K, Moore DD, Yechoor VK (2013). Bmal1 and β-cell clock are required for adaptation to circadian disruption, and their loss of function leads to oxidative stress-induced β-cell failure in mice. Mol. Cell Biol. 33: 2327-38. PubMed PMID: 23547261
- Xu Z, Poidevin M, Li X, Li Y, Shu L, Nelson DL, Li H, Hales CM, Gearing M, Wingo TS, Jin P (2013). Expanded GGGGCC repeat RNA associated with amyotrophic lateral sclerosis and frontotemporal dementia causes neurodegeneration. Proc. Natl. Acad. Sci. U S A 110: 7778-83. PubMed PMID: 23553836
- Vislay RL, Martin BS, Olmos-Serrano JL, Kratovac S, Nelson DL, Corbin JG, Huntsman MM (2013). Homeostatic responses fail to correct defective amygdala inhibitory circuit maturation in fragile X syndrome. J. Neurosci. 33: 7548-58. PubMed PMID: 23616559
- Yrigollen CM, Durbin-Johnson B, Gane L, Nelson DL, Hagerman R, Hagerman PJ, Tassone F (2012). AGG interruptions within the maternal FMR1 gene reduce the risk of offspring with fragile X syndrome. Genet. Med. 14: 729-36. PubMed PMID: 22498846
- Qurashi A, Liu H, Ray L, Nelson DL, Duan R, Jin P (2012). Chemical screen reveals small molecules suppressing fragile X premutation rCGG repeat-mediated neurodegeneration in Drosophila. Hum. Mol. Genet. 21: 2068-75. PubMed PMID: 22298836
- Tan H, Qurashi A, Poidevin M, Nelson DL, Li H, Jin P (2012). Retrotransposon activation contributes to fragile X premutation rCGG-mediated neurodegeneration. Hum. Mol. Genet. 21: 57-65. PubMed PMID: 21940752
- Whitman SA, Cover C, Yu L, Nelson DL, Zarnescu DC, Gregorio CC (2011). Desmoplakin and Talin2 Are Novel mRNA Targets of Fragile X-Related Protein-1 in Cardiac Muscle. Circ. Res. 109: 262-271. PubMed PMID: 21659647
- Guo W, Allan AM, Zong R, Zhang L, Johnson EB, Schaller EG, Murthy AC, Goggin SL, Eisch AJ, Oostra BA, Nelson DL, Jin P, Zhao X (2011). Ablation of Fmrp in adult neural stem cells disrupts hippocampus-dependent learning. Nat. Med. 17(5): 559-565. PubMed PMID: 21516088
- Hashem V, Galloway JN, Mori M, Willemsen R, Oostra BA, Paylor R, Nelson DL (2009). Ectopic expression of CGG containing mRNA is neurotoxic in mammals. Hum. Mol. Genet. 18(13): 2443-51. PubMed PMID: 19377084
- Zhang J, Hou L, Klann E, Nelson DL (2009). Altered hippocampal synaptic plasticity in the FMR1 gene family knockout mouse models. J. Neurophysiol. 101(5): 2572-80. PubMed PMID: 19244359
- Sofola OA, Sundram V, Kleyner Y, Morales J, Botas J, Jackson FR, Nelson DL (2008). The Drosophila FMRP and LARK RNA-binding proteins function together to regulate eye development and circadian behavior. J. Neurosci. 28(41): 10200-5. PubMed PMID: 18842880
- Zhang J, Fang Z, Lee CC, Albrecht U, Oostra B, Nelson DL (2008). Fragile X proteins regulate mammalian circadian behavior. Am. J. Hum. Genet. 83(1): 43-52. PubMed PMID: 18589395
Awards and Honors
2012: Editor-in-chief, American Journal of Human Genetics
2010: Barbara Bowman Distinguished Texas Geneticist Award
2004: Secretary, American Society of Human Genetics
2003: Cullen Foundation Chair in Molecular and Human Genetics
2000-2003: National Institute of Child Health and Human Development (NICHD) - Member, Mental Retardation Review Committee
2000: Huntington Disease Society of America - Leadership Award
2000: National Fragile-X Foundation - William Rosen Award
David L. Nelson, Ph.D.
Department of Molecular and Human Genetics
Baylor College of Medicine
One Baylor Plaza, MS BCM225
Houston, TX, 77030, U.S.A.