David L. Nelson

David L. Nelson (born 1956) is an American human geneticist, currently an associate director at the Intellectual and Developmental Disabilities Research Center (1995), and professor at the Department of Molecular and Human Genetics at Baylor College of Medicine BCM since 1999. Since 2018, he is the director at the Cancer and Cell Biology Ph.D program, and the director of Integrative Molecular and Biomedical Sciences Ph.D since 2015 at BMC.[1][2]

David L. Nelson
Born1956
Washington DC
Alma materUniversity of Virginia (BA)
Massachusetts Institute of Technology MIT (PhD, Postdoc)
Baylor College of Medicine (Postdoc)
AwardsWilliam Rosen Award (2000)
Huntington Disease Society of America Leadership Award (200)
Barbara Bowman Distinguished Geneticist (2010)
Scientific career
FieldsMolecular genetics, Human genome, Segmental duplication, Gene duplication
InstitutionsUniversity of Virginia
MIT Department of Biology
National Institute of Neurological Disorders and Stroke
Baylor College of Medicine
ThesisChromosome Transfer of Introduced Selectable Markers: Use in Gene Mapping and Isolation" Thesis Project, MIT, with Dr. David Housman) (1984)

Education and career

Nelson received a bachelor's degree from the University of Virginia in 1978 and received his PhD in molecular genetics from the Massachusetts Institute of Technology in 1984. He carried out his postdoctoral training at Massachusetts Institute of Technology (1984–1985) and National Institutes of Health before moving to Baylor College of Medicine.

Nelson joined the MIT Center for Cancer Research (CCR) group of David Housman at the Massachusetts Institute of Technology as a postdoctoral trainee (1986–1989). Nelson's work using introduced selectable genes expanded approaches to whole human genome mapping. From 1984 to 1985, in an intramural National Institutes of Health program at the laboratory of Robert Lazzarini, Nelson studied neuroscience and defined genes encoding neurofilament proteins. In 1986 he joined the C. Thomas Caskey laboratory at the Institute of Molecular Genetics, Baylor College of Medicine.[3]

Applying the Polymerase chain reaction PCR, a technique that allows rapid gene mapping and isolation of specific chromosomal regions, Nelson et al. identified chromosomal locations of large fragments of the human X chromosome;[4] Nelson contributed to the human, mouse and fly reference sequences and was a co-discoverer of the mutation that causes Fragile X syndrome as an expansion of a trinucleotide repeat in the FMR1 gene.[5] Nelson's contributions have led to the description of Lowe syndrome,[6] and the identification of FMR2 for FRAXE syndrome.[7]

Contributions to science

Human Genome Project

Nelson's molecular techniques led to the development of genome mapping and sequencing and discovery of disease genes, contributing efforts to map and sequence of the human X chromosome. He was a leader in genetic and genomic analyses across all species.[4][8][9][10]

Incontinentia Pigmenti (IP)

With a group of international collaborators, Nelson's research group was able to identify a recurrent, homology-driven deletion in the NEMO gene in Incontinentia pigmenti (IP), an X-linked genetic disease.[11][12][13][14] [15]

Unstable repeats as mutations in human genetic disease

Nelson and other collaborators at BMC, Emory University, and Erasmus University Rotterdam identified a massive expansion of CGG repeat (Trinucleotide repeat disorder) in FMR1. This was the first to be identified as the underlying mutations in human genetic disorders. Their findings in FMR1 explained the unusual inheritance in Fragile X syndrome and provided the principles for all subsequent unstable repeat disorders such as myotonic dystrophy, Huntington's disease, and amyotrophic lateral sclerosis.[5][16][17][18]

FMR1 in neuronal function

By studying humans, mice, flies and yeast Nelson's research group has characterized the origins of instability in the repeat, the consequences of "premutation" length expansions, and the function of FMR1 and related FXR1 and FXR2. Nelson and his research group have defined roles for FMR1 and paralogs in circadian rhythm, energy metabolism, neuronal stem cell development, and microRNA function. Their research results are being used in research to define the role of FMR1 in development and potential treatment for these diseases in adulthood.[19][20][21][22][23]

Fragile X tremor ataxia syndrome (FXTAS)

FXTAS individuals are cognitively unaffected until they reach their 60 or 70, when they show neural degeneration and nuclear inclusions during autopsy. Nelson's research group has used flies and mice to identify and characterize modifiers that showed that the CGG repeat is necessary and sufficient to affect mammalian neurons. Models developed by Nelson's research group have improved the understanding of mechanisms of this disease, including a role for RNA-binding functions such as TDP-43 and alterations in 5-Hydroxymethylcytosine.[24][25][26][27]

Public service

Nelson is a member of the Board of Directors of the American Society of Human Genetics, was its President in 2018, and served as Secretary from 2003 to 2009.

Nelson has served in many advisory boards and committees, including FRAXA Research Foundation Advisory Board (1999–present), National Fragile X Foundation Advisory Board (1999–present), March of Dimes Grants Review Board (2010–2015), Hungtinton Disease Society of America Steering Committee (1999–2010), United States NIH/NICHD Mental Retardation Review Committee (1998–2002), and US DOE Joint Genome Institute Advisory Board (1997–2000).

Nelson served on the editorial boards of eleven academic journals, including American Journal of Human Genetics, Mammalian Genome, Clinical Genetics (journal), and Genome Research.

Patents

6824972. Diagnosis and treatment of medical conditions associated with defective NFkappa B (NF-κB) activation. [28]

6107025. Diagnosis of the fragile X syndrome.[29]

Awards and honors

References
  1. "David L Nelson - Google Scholar Citations". scholar.google.com.
  2. "My Bibliography - My NCBI Collection". ncbi.nlm.nih.gov. Retrieved 2019-06-26.
  3. "Issue: The American Journal of Human Genetics". www.cell.com.
  4. Nelson, D. L.; Ledbetter, S. A.; Corbo, L.; Victoria, M. F.; Ramirez-Solis, R.; Webster, T. D.; Ledbetter, D. H.; Caskey, C. T. (1 September 1989). "Alu polymerase chain reaction: a method for rapid isolation of human-specific sequences from complex DNA sources". Proceedings of the National Academy of Sciences. 86 (17): 6686–6690. Bibcode:1989PNAS...86.6686N. doi:10.1073/pnas.86.17.6686. PMC 297910. PMID 2771952.
  5. Verkerk, Annemieke J.M.H.; Pieretti, Maura; Sutcliffe, James S.; Fu, Ying-Hui; Kuhl, Derek P.A.; Pizzuti, Antonio; Reiner, Orly; Richards, Stephen; Victoria, Maureen F.; Zhang, Fuping; Eussen, Bert E.; van Ommen, Gert-Jan B.; Blonden, Lau A.J.; Riggins, Gregory J.; Chastain, Jane L.; Kunst, Catherine B.; Galjaard, Hans; Thomas Caskey, C.; Nelson, David L.; Oostra, Ben A.; Warren, Stephen T. (May 1991). "Identification of a gene (FMR-1) containing a CGG repeat coincident with a breakpoint cluster region exhibiting length variation in fragile X syndrome". Cell. 65 (5): 905–914. doi:10.1016/0092-8674(91)90397-H. PMID 1710175.
  6. Attree, Olivier; Olivos, Isabelle M.; Okabe, Ichiro; Bailey, L. Charles; Nelson, David L.; Lewis, Richard A.; Mclnnes, Roderick R.; Nussbaum, Robert L. (July 1992). "The Lowe's oculocerebrorenal syndrome gene encodes a protein highly homologous to inositol polyphosphate-5-phosphatase". Nature. 358 (6383): 239–242. Bibcode:1992Natur.358..239A. doi:10.1038/358239a0. PMID 1321346.
  7. Gu, Yanghong; Shen, Ying; Gibbs, Richard A.; Nelson, David L. (May 1996). "Identification of FMR2, a novel gene associated with the FRAXE CCG repeat and CpG island". Nature Genetics. 13 (1): 109–113. doi:10.1038/ng0596-109.
  8. Adams, Mark D., George L. Gabor Miklos, Angela Center, Robert D. C. Saunders, Susan E. Celniker, Robert A. Holt, Cheryl A. Evans, et al. 2000. "The Genome Sequence of Drosophila melanogaster". Science. 287 (5461): 2185–2195. DOI: https://doi.org/10.1126/science.287.5461.2185
  9. Lander, Eric S.; Linton, Lauren M.; Birren, Bruce; Nusbaum, Chad; Zody, Michael C.; Baldwin, Jennifer; Devon, Keri; Dewar, Ken; Doyle, Michael; Fitzhugh, William; Funke, Roel; Gage, Diane; Harris, Katrina; Heaford, Andrew; Howland, John; Kann, Lisa; Lehoczky, Jessica; Levine, Rosie; McEwan, Paul; McKernan, Kevin; Meldrim, James; Mesirov, Jill P.; Miranda, Cher; Morris, William; Naylor, Jerome; Raymond, Christina; Rosetti, Mark; Santos, Ralph; Sheridan, Andrew; et al. (February 2001). "Initial sequencing and analysis of the human genome". Nature. 409 (6822): 860–921. Bibcode:2001Natur.409..860L. doi:10.1038/35057062.
  10. Ross, Mark T.; Grafham, Darren V.; Coffey, Alison J.; Scherer, Steven; McLay, Kirsten; Muzny, Donna; Platzer, Matthias; Howell, Gareth R.; Burrows, Christine; Bird, Christine P.; Frankish, Adam; Lovell, Frances L.; Howe, Kevin L.; Ashurst, Jennifer L.; Fulton, Robert S.; Sudbrak, Ralf; Wen, Gaiping; Jones, Matthew C.; Hurles, Matthew E.; Andrews, T. Daniel; Scott, Carol E.; Searle, Stephen; Ramser, Juliane; Whittaker, Adam; Deadman, Rebecca; Carter, Nigel P.; Hunt, Sarah E.; Chen, Rui; Cree, Andrew; et al. (March 2005). "The DNA sequence of the human X chromosome". Nature. 434 (7031): 325–337. Bibcode:2005Natur.434..325R. doi:10.1038/nature03440. PMC 2665286. PMID 15772651.
  11. Julia E. Parrish, Angela E. Scheuerle, Richard A. Lewis, Moise L. Levy, David L. Nelson (1996). Selection Against Mutant Alleles in Blood Leukocytes is a Consistent Feature in Incontinentia Pigmenti Type 2. Human Molecular Genetics, 5 (11):1777–1783. DOI: https://doi.org/10.1093/hmg/5.11.1777
  12. Smahi, Asmae; Courtois, G.; Vabres, P.; Yamaoka, S.; Heuertz, S.; Munnich, A.; Israël, A.; Heiss, Nina S.; Klauck, S. M.; Kioschis, P.; Wiemann, S.; Poustka, A.; Esposito, Teresa; Bardaro, T.; Gianfrancesco, F.; Ciccodicola, A.; d'Urso, M.; Woffendin, Hayley; Jakins, T.; Donnai, D.; Stewart, H.; Kenwrick, S. J.; Aradhya, Swaroop; Yamagata, T.; Levy, M.; Lewis, R. A.; Nelson, D. L. (May 2000). "Genomic rearrangement in NEMO impairs NF-κB activation and is a cause of incontinentia pigmenti". Nature. 405 (6785): 466–472. Bibcode:2000Natur.405..466T. doi:10.1038/35013114. PMID 10839543.
  13. Aradhya, S. (1 September 2001). "A recurrent deletion in the ubiquitously expressed NEMO (IKK-gamma) gene accounts for the vast majority of incontinentia pigmenti mutations". Human Molecular Genetics. 10 (19): 2171–2179. doi:10.1093/hmg/10.19.2171. PMID 11590134.
  14. Swaroop Aradhya, Hayley Woffendin, Tracy Jakins, Tiziana Bardaro, Teresa Esposito, Asmae Smahi, Christine Shaw, Moise Levy, Arnold Munnich, Michele D’Urso, Richard A. Lewis, Sue Kenwrick, David L. Nelson (2001). A recurrent deletion in the ubiquitously expressed NEMO (IKK-γ) gene accounts for the vast majority of incontinentia pigmenti mutations, Human Molecular Genetics. 10(19):2171–2179, https://doi.org/10.1093/hmg/10.19.2171
  15. Swaroop Aradhya, Tiziana Bardaro, Petra Galgóczy, Takanori Yamagata, Teresa Esposito, Henry Patlan, Alfredo Ciccodicola, Arnold Munnich, Sue Kenwrick, Matthias Platzer, Michele D’Urso, David L. Nelson (2001). Multiple pathogenic and benign genomic rearrangements occur at a 35 kb duplication involving the NEMO and LAGE2 genes. Human Molecular Genetics 10(22):2557–2567. DOI: https://doi.org/10.1093/hmg/10.22.2557
  16. Pieretti, Maura; Zhang, Fuping; Fu, Ying-Hui; Warren, Stephen T.; Oostra, Ben A.; Caskey, C.Thomas; Nelson, David L. (August 1991). "Absence of expression of the FMR-1 gene in fragile X syndrome". Cell. 66 (4): 817–822. doi:10.1016/0092-8674(91)90125-I.
  17. Fu, Ying-Hui; Kuhl, Derek P.A.; Pizzuti, Antonio; Pieretti, Maura; Sutcliffe, James S.; Richards, Stephen; Verkert, Annemieke J.M.H.; Holden, Jeanette J.A.; Fenwick, Raymond G.; Warren, Stephen T.; Oostra, Ben A.; Nelson, David L.; Caskey, C.Thomas (December 1991). "Variation of the CGG repeat at the fragile X site results in genetic instability: Resolution of the Sherman paradox". Cell. 67 (6): 1047–1058. doi:10.1016/0092-8674(91)90283-5.
  18. Eichler, Evan E.; Holden, Jeanette J.A.; Popovich, Bradley W.; Reiss, Allan L.; Snow, Karen; Thibodeau, Stephen N.; Richards, C. Sue; Ward, Patricia A.; Nelson, David L. (September 1994). "Length of uninterrupted CGG repeats determines instability in the FMR1 gene". Nature Genetics. 8 (1): 88–94. doi:10.1038/ng0994-88.
  19. Jin, Peng; Zarnescu, Daniela C; Ceman, Stephanie; Nakamoto, Mika; Mowrey, Julie; Jongens, Thomas A; Nelson, David L; Moses, Kevin; Warren, Stephen T (4 January 2004). "Biochemical and genetic interaction between the fragile X mental retardation protein and the microRNA pathway". Nature Neuroscience. 7 (2): 113–117. doi:10.1038/nn1174.
  20. Zhang, Jing; Fang, Zhe; Jud, Corinne; Vansteensel, Mariska J.; Kaasik, Krista; Lee, Cheng Chi; Albrecht, Urs; Tamanini, Filippo; Meijer, Johanna H.; Oostra, Ben A.; Nelson, David L. (July 2008). "Fragile X-Related Proteins Regulate Mammalian Circadian Behavioral Rhythms". The American Journal of Human Genetics. 83 (1): 43–52. doi:10.1016/j.ajhg.2008.06.003. PMC 2443847.
  21. Guo, Weixiang; Allan, Andrea M; Zong, Ruiting; Zhang, Li; Johnson, Eric B; Schaller, Eric G; Murthy, Adeline C; Goggin, Samantha L; Eisch, Amelia J; Oostra, Ben A; Nelson, David L; Jin, Peng; Zhao, Xinyu (24 April 2011). "Ablation of Fmrp in adult neural stem cells disrupts hippocampus-dependent learning". Nature Medicine. 17 (5): 559–565. doi:10.1038/nm.2336. PMC 3140952. PMID 21516088.
  22. Lumaban, J. G.; Nelson, D. L. (30 December 2014). "The Fragile X proteins Fmrp and Fxr2p cooperate to regulate glucose metabolism in mice". Human Molecular Genetics. 24 (8): 2175–2184. doi:10.1093/hmg/ddu737. PMC 4380067. PMID 25552647.
  23. Higashimori, H.; Schin, C. S.; Chiang, M. S. R.; Morel, L.; Shoneye, T. A.; Nelson, D. L.; Yang, Y. (6 July 2016). "Selective Deletion of Astroglial FMRP Dysregulates Glutamate Transporter GLT1 and Contributes to Fragile X Syndrome Phenotypes In Vivo". Journal of Neuroscience. 36 (27): 7079–7094. doi:10.1523/JNEUROSCI.1069-16.2016. PMC 4938857. PMID 27383586.
  24. Sofola, Oyinkan A.; Jin, Peng; Qin, Yunlong; Duan, Ranhui; Liu, Huijie; de Haro, Maria; Nelson, David L.; Botas, Juan (August 2007). "RNA-Binding Proteins hnRNP A2/B1 and CUGBP1 Suppress Fragile X CGG Premutation Repeat-Induced Neurodegeneration in a Drosophila Model of FXTAS". Neuron. 55 (4): 565–571. doi:10.1016/j.neuron.2007.07.021. PMC 2215388. PMID 17698010.
  25. Nelson, David L.; Paylor, Richard; Oostra, Ben A.; Willemsen, Rob; Mori, Mayra; Galloway, Jocelyn N.; Hashem, Vera (1 July 2009). "Ectopic expression of CGG containing mRNA is neurotoxic in mammals". Human Molecular Genetics. 18 (13): 2443–2451. doi:10.1093/hmg/ddp182. ISSN 0964-6906. PMID 19377084.
  26. Yao, Bing; Lin, Li; Street, R. Craig; Zalewski, Zachary A.; Galloway, Jocelyn N.; Wu, Hao; Nelson, David L.; Jin, Peng (15 February 2014). "Genome-wide alteration of 5-hydroxymethylcytosine in a mouse model of fragile X-associated tremor/ataxia syndrome". Human Molecular Genetics. 23 (4): 1095–1107. doi:10.1093/hmg/ddt504. PMID 24108107.
  27. Galloway, Jocelyn N.; Shaw, Chad; Yu, Peng; Parghi, Deena; Poidevin, Mickael; Jin, Peng; Nelson, David L. (15 November 2014). "CGG repeats in RNA modulate expression of TDP-43 in mouse and fly models of fragile X tremor ataxia syndrome". Human Molecular Genetics. 23 (22): 5906–5915. doi:10.1093/hmg/ddu314. PMID 24986919.
  28. Kenwrick, Sue J.; Woffendin, Hayley; Munnich, Arnold; Smahi, Asmae; Israel, Alain; Poustka, Annemarie; Heiss, Nina; D'Urso, Michele; Lewis, Richard A.; Nelson, David L.; Aradhya, Swaroop; Levy, Moise (2004). "United States Patent: 6824972 - Diagnosis and treatment of medical conditions associated with defective NFkappa B(NF-.kappa.B) activation".
  29. Caskey, C. Thomas; Nelson, David L.; Pieretti, Maura; Warren, Stephen T.; Oostra, Ben A. (2000). "United States Patent: 6107025 - Diagnosis of the fragile X syndrome".
  30. http://www.texasgeneticssociety.org/wp-content/uploads/2019/04/Barabara-Bowman-Award-Recipients.pdf
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