Lawrence T. Reiter, Ph.D.
Department of Neurology
Department of Anatomy and Neurobiology
The University of Tennessee Health Science Center
855 Monroe Avenue, Suite 415
Memphis, TN 38163
Phone: (901) 448-2635
Office: (901) 448-7443
Fax: (901) 448-7440
Lab: 431 Johnson Building
Email: Lawrence T. Reiter
- Ph.D. Institution: Department of Cell and Molecular Biology, Baylor College of Medicine
- Postdoctoral: University of California San Diego
- Tooth Study
- Homophila Database
- Negative Proteome Database
- Duplication 15q Alliance
- GoogleScholar H-Index
My laboratory utilizes the powerful genetic model organism Drosophila melanogaster (fruit flies) to investigate the functions of genes involved in human neurological disease. Our main focus is the study of genes related to Angelman syndrome and autism spectrum disorders. These disorders are interrelated at the molecular level and one of the goals of our laboratory is to identify genes and proteins regulated by one or more of the proteins that, when mutated, can cause and autism phenotype. In addition, approximately 3-5 % of all autism cases result from maternally derived duplications of the region containing the gene that causes AS, UBE3A. Mutations in the protein targets of the ubiquitin ligase UBE3A may therefore account for a significant percentage of idiopathic autism cases.
In our laboratory we utilize Drosophila specific genetic techniques that allow us to generate artificially high levels of normal and mutant fly Dube3a proteins in fly heads. Wild type, dominant negative and epitope tagged forms of ube3a are over-expressed in the brains of flies using the GAL4/UAS system in order to increase or decrease the levels of ube3a protein targets. We have now identified 50 of these potential Dube3a regulated proteins and are actively validating these interactions using whole genome molecular methods (genomics), genetic suppressor/enhancer screens, immunostaining in fly neurons (immunoflourescence), and changes in synaptic function and stability at the fly neuromuscular junction (electrophysiology). Using these methodologies in flies we have identified Dube3a regulation of the actin cytoskeleton (Reiter et al. Hum Mol Genet. 2006 Sep 15;15(18):2825-35) as well as the synthesis of monoamines (Ferdousy et al Neurobiol Dis. 2011 Mar;41(3):669-77).
Another aspect of our work is related to describing various quantifiable behavior phenotypes in Ube3a deficient and over-expressing mice. Specifically, we are interested in abnormal social behavior (a measure of autistic behavior in mice) as well as abnormal fluid licking behavior (a natural behavior which reflects cerebellar function). These experiments have already shown that Ube3a deficient animals have measurable deficits in fluid licking that are directly related to the decrease in Ube3a levels in the brain (Heck et al. Hum Mol Genet. 17(14):2181-9) as well as hypoactivity and defects in exploratory behavior in the Ube3a deficient animals (Allensworth et al. BMC Genet. 2011 Jan 14;12:7).
Finally, we have been doing in depth phenotypic and molecular analysis of individuals with interstitial duplication 15q autism. Since 2007 we have been collecting a variety of language, neuropsychiatric, neurological and gene expression data from subjects with interstitial 15q chromosomal duplications. We hope that our basic research into the functional targets of UBE3A will lead to a better understanding of the phenotypes in this particular autism population where the UBE3A gene is duplicated, and presumably expressed at higher levels than in unaffected individuals. For more information on our clinical study see http://www.idic15.org/Dr-Reiter.html. As an extension of this work which bridges the gap between basic and clinical research, we recently began an NIH funded study to generate dental pulp derived neruons from individuals with either the Angelman syndrome deletion in this region or a duplication of this region on chromosome 15q causing autism. We hope that these patient-derive neuronal cultures will allow us to perform more in depth molecular and electrophysiological analysis of both conditions in the near future. For more information on the dental pulp stem cell study please see http://tinyurl.com/88f688l.
- Hatfield I, Harvey I, Yates ER, Redd JR, Reiter LT, Bridges D. The role of TORC1 in muscle development in Drosophila. Sci Rep. 2015 Apr 13;5:9676. doi: 10.1038/srep09676. PubMed PMID: 25866192.
- Germain ND, Chen PF, Plocik AM, Glatt-Deeley H, Brown J, Fink JJ, Bolduc KA, Robinson TM, Levine ES, Reiter LT, Graveley BR, Lalande M, Chamberlain SJ. Gene expression analysis of human induced pluripotent stem cell-derived neurons carrying copy number variants of chromosome 15q11-q13.1. Mol Autism. 2014 Aug 20;5:44. doi: 10.1186/2040-2392-5-44. eCollection 2014. PubMed PMID: 25694803; PubMed Central PMCID: PMC4332023.
- Conant KD, Finucane B, Cleary N, Martin A, Muss C, Delany M, Murphy EK, Rabe O, Luchsinger K, Spence SJ, Schanen C, Devinsky O, Cook EH, LaSalle J, Reiter LT, Thibert RL. A survey of seizures and current treatments in 15q duplication syndrome. Epilepsia. 2014 Mar;55(3):396-402. doi: 10.1111/epi.12530. Epub 2014 Feb 6. PubMed PMID: 24502430.
- Jensen L, Farook MF, Reiter LT. Proteomic profiling in Drosophila reveals potential Dube3a regulation of the actin cytoskeleton and neuronal homeostasis. PLoS One. 2013 Apr 23;8(4):e61952. doi: 10.1371/journal.pone.0061952. Print 2013. PubMed PMID: 23626758; PubMed Central PMCID: PMC3633955.
- Urraca N, Cleary J, Brewer V, Pivnick EK, McVicar K, Thibert RL, Schanen NC, Esmer C, Lamport D, Reiter LT. The interstitial duplication 15q11.2-q13 syndrome includes autism, mild facial anomalies and a characteristic EEG signature. Autism Res. 2013 Aug;6(4):268-79. doi: 10.1002/aur.1284. Epub 2013 Mar 14. PubMed PMID: 23495136; PubMed Central PMCID: PMC3884762.
- Farook MF, DeCuypere M, Hyland K, Takumi T, LeDoux MS, Reiter LT. Altered serotonin, dopamine and norepinepherine levels in 15q duplication and Angelman syndrome mouse models. PLoS One. 2012;7(8):e43030. doi: 10.1371/journal.pone.0043030. Epub 2012 Aug 16. PubMed PMID: 22916201; PubMed Central PMCID: PMC3420863.