Positions
- Professor
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Molecular and Human Genetics
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Houston, TX, US
- Director
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Graduate Program in Cancer & Cell Biology
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- Director
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Graduate Program in Integrative Molecular and Biomedical Sciences
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- The Cullen Foundation Professorship in Molecular Genetics
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91¹ú²úÊÓƵ
Houston, Texas, United States
- Member
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Dan L Duncan Comprehensive Cancer Center
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Houston, Texas, United States
- Director
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BCM Michigan Emory Fragile X Research Center
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NIH funded Center aimed at understanding mechanisms whereby premutation-length CGG repeats cause neurodegenerative and ovarian disorders.
Education
- PhD from Massachusetts Institute Of Technology
- 06/1984 - Cambridge, Massachusetts, United States
- Biology
- Post-Doctoral Fellowship at National Institutes Of Health
- 01/1985 - Bethesda, MD, United States
- Post-Doctoral Fellowship at Baylor College Of Medicine
- 01/1986 - Houston, TX, United States
- BA from University Of Virginia
- 05/1978 - Charlottesville, Virginia, United States
- Biology, Chemistry
Honors & Awards
- Editor-in-chief, American Journal of Human Genetics
- American Society of Human Genetics (01/2012 - 12/2017)
- Barbara Bowman Distinguished Texas Geneticist Award
- 2010
- Secretary, American Society of Human Genetics
- (01/2004 - 12/2009)
- Cullen Foundation Chair in Molecular and Human Genetics
- 2003
- National Institute of Child Health and Human Development (NICHD) - Member, Mental Retardation Review Committee
- 2003
- Huntington Disease Society of America - Leadership Award
- 2000
- National Fragile-X Foundation - William Rosen Award
- 2000
- AAAS Fellow
- 2015
- AAAS
- President
- American Society of Human Genetics (01/2018 - 12/2018)
Professional Interests
- Human genome and disease gene analysis
- Fragile X syndrome
- Incontinentia pigmenti
- Complex genetics
Professional Statement
RESEARCH INTERESTS
One of the most exciting findings in human genetics has been the recognition that unstable trinucleotide repeats contribute to more than four dozen genetic disorders, including myotonic muscular dystrophy, amyotrophic lateral sclerosis (Lou Gehrig's disease) and Huntington’s disease. With collaborators, Nelson described the first of these unstable DNA sequences, a polymorphic CGG trinucleotide repeat in the FMR1 gene found to be enlarged in people with fragile X syndrome, the most common form of inherited intellectual disability and autism. The mechanism by which this mutation leads to disease is through loss of function of the FMR1 gene product due to diminished expression accompanied by aberrant methylation of the gene. The FMR1 gene product is an RNA binding protein that interacts with complexes of RNA and ribosomes. It regulates the translation of hundreds of mRNAs. The Nelson group focuses on dissecting the function(s) of FMR1 and its paralogs FXR1 and FXR2. Understanding factors that lead to DNA instability of this sequence is also a key interest.
The Nelson group also studies disorders found in people with smaller expansions of the FMR1 CGG repeat, known as premutation carriers (55-200 repeats). Males with CGG repeat lengths in this range are at risk for a late-onset neurodegenerative disorder termed FXTAS. FXTAS is distinct from fragile X syndrome; individuals are cognitively unaffected until their 6th or 7th decade, but then show neuronal degeneration accompanied by neuronal nuclear inclusions that stain with ubiquitin on autopsy. The Nelson group has utilized models in flies and mice to investigate the hypothesis that a gain of function through RNA toxicity is responsible for neuronal dysfunction and death. Fly models allowed identification and characterization of modifiers, and mouse models showed definitively that the CGG repeat was both necessary and sufficient to affect mammalian neurons. The group is also studying fragile X-associated primary ovarian insufficiency, (FXPOI) a disorder resulting in early menopause found in some female carriers of the premutation. Using mouse models, the group has improved understanding of the mechanism of ovarian insufficiency. Identifying genetic modifiers in both FXTAS and FXPOI is a goal for potential therapies. The group has demonstrated roles for several RNA-binding proteins including TDP-43 and alterations in 5-hydroxymethylcytosine, suggesting widespread dysregulation of gene expression.
The Nelson group was 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 fruit fly to Rhesus monkey. Dr. Nelson's group identified gene mutations in other disorders such as Incontinentia Pigmenti and FRAXE intellectual disability. He 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.
One of the most exciting findings in human genetics has been the recognition that unstable trinucleotide repeats contribute to more than four dozen genetic disorders, including myotonic muscular dystrophy, amyotrophic lateral sclerosis (Lou Gehrig's disease) and Huntington’s disease. With collaborators, Nelson described the first of these unstable DNA sequences, a polymorphic CGG trinucleotide repeat in the FMR1 gene found to be enlarged in people with fragile X syndrome, the most common form of inherited intellectual disability and autism. The mechanism by which this mutation leads to disease is through loss of function of the FMR1 gene product due to diminished expression accompanied by aberrant methylation of the gene. The FMR1 gene product is an RNA binding protein that interacts with complexes of RNA and ribosomes. It regulates the translation of hundreds of mRNAs. The Nelson group focuses on dissecting the function(s) of FMR1 and its paralogs FXR1 and FXR2. Understanding factors that lead to DNA instability of this sequence is also a key interest.
The Nelson group also studies disorders found in people with smaller expansions of the FMR1 CGG repeat, known as premutation carriers (55-200 repeats). Males with CGG repeat lengths in this range are at risk for a late-onset neurodegenerative disorder termed FXTAS. FXTAS is distinct from fragile X syndrome; individuals are cognitively unaffected until their 6th or 7th decade, but then show neuronal degeneration accompanied by neuronal nuclear inclusions that stain with ubiquitin on autopsy. The Nelson group has utilized models in flies and mice to investigate the hypothesis that a gain of function through RNA toxicity is responsible for neuronal dysfunction and death. Fly models allowed identification and characterization of modifiers, and mouse models showed definitively that the CGG repeat was both necessary and sufficient to affect mammalian neurons. The group is also studying fragile X-associated primary ovarian insufficiency, (FXPOI) a disorder resulting in early menopause found in some female carriers of the premutation. Using mouse models, the group has improved understanding of the mechanism of ovarian insufficiency. Identifying genetic modifiers in both FXTAS and FXPOI is a goal for potential therapies. The group has demonstrated roles for several RNA-binding proteins including TDP-43 and alterations in 5-hydroxymethylcytosine, suggesting widespread dysregulation of gene expression.
The Nelson group was 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 fruit fly to Rhesus monkey. Dr. Nelson's group identified gene mutations in other disorders such as Incontinentia Pigmenti and FRAXE intellectual disability. He 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.
Selected Publications
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Kang JY, Wen Z, Pan D, Zhang Y, Li Q, (…), Nelson DL, Guo X, Zhou Y, Gou LT, Huang Y, Liu MF. " " Science. 2022 ; 377 : eabj6647.
Pubmed PMID: . -
Yildirim Z, Baboo S, Hamid SM, Dogan AE, Tufanli O, (…), Nelson DL, Yates JR 3rd, Walter P, Erbay E. " " EMBO Mol Med.. 2022 ; 14 : e15344.
Pubmed PMID: . -
Kong HE, Lim J, Linsalata A, Kang Y, Malik I, (…), Nelson DL, Epstein MP, Cutler DJ, Todd PK, Sherman SL, Warren ST, Jin. " " Proc Natl Acad Sci U S A. 2022 ; 119 : e2118124119.
Pubmed PMID: . -
Shelly KE, Candelaria NR, Li Z, Allen EG, Jin P, Nelson DL. " Ectopic expression of CGG-repeats alters ovarian response to gonadotropins and leads to infertility in a murine FMR1 premutation model.. " Hum Mol Genet.. 2021 ; 30 : 923-938.
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