LAWRENCE T. REITER, Ph.D.
Associate Professor, Department of Neurology
Adjunct Associate Professor, Department of Pediatrics
Adjunct Associate Professor, Department of Anatomy and Neurobiology
Director, Drosophila Transgenic Core
431 Johnson Building
- PostDoc, University of California, San Diego, CA, Drosophila genetics
- PostDoc, Baylor College of Medicine, Houston, TX, Charcot Marie Tooth Fellow
- Ph.D., Baylor College of Medicine, Houston, TX, Cell and Molecular Biology
- B.S., University of Southern California, Los Angeles, CA, Molecular Biology
Genetic and biochemical analysis of autism spectrum disorders.
Autism, Angelman syndrome, UBE3A, Drosophila genetics, proteomics
Area of teaching/subject
Model Organism Genetics
Autism Spectrum Disorders
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 autism and autism spectrum disorders. Autism spectrum disorders include the severely debilitating fragile X, Rett (RTT) and Angelman syndromes (AS). These disorders appear to be interrelated at the molecular level one of the goals of our laboratory is to identify genes and proteins regulated by one or more of the proteins that, when mutated, cause fragile X, RTT or AS. In addition, approximately 3 % of all inherited autism cases may result from maternally inherited duplications of the region containing the gene that causes AS, UBE3A. Mutations in the protein targets of the ubiquitin ligase UBE3A, the transcriptional regulator MECP2 or the transcripts regulated by the fragile X gene FMRP, may account for a significant percentage of inherited autism cases.
In our laboratory we utilize Drosophila specific genetic techniques that allow us to generate artificially high levels of normal and mutant fly ube3a 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 then identify these targets by 2 D gel electrophoresis and mass spectrometry (proteomics). Potential targets are then validated though genetic suppressor/enhancer screens, looking for changes in fly neurons after deletion of these target genes, immunoprecipitation binding assays in cell culture and immunohistochemistry in the brains of the appropriate mouse models.
Another aspect of our work is related to describing various quantifiable behavior phenotypes in Ube3a, Fmr1 and Mecp2 deficient 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 expression levels in the brain (Heck DH, Zhao Y, Roy S, LeDoux MS, Reiter LT. 2008. Analysis of cerebellar function in Ube3a-deficient mice reveals novel genotype-specific behaviors. Hum Mol Genet. 17(14):2181-9).
An important additional area of our research is the 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/res_cur_reiter.php.
- Roy, S, Zhao, Y, Allensworth, M, Farook, MF, Ledoux, MS, Reiter, LT, Heck, DH. Comprehensive motor testing in Fmr1-KO mice exposes temporal defects in oromotor coordination. Behav Neurosci, 125 (6), 962-9, 2011.
- Scoles, HA, Urraca, N, Chadwick, SW, Reiter, LT, Lasalle, JM. Increased copy number for methylated maternal 15q duplications leads to changes in gene and protein expression in human cortical samples. Mol Autism, 2 (1), 19, 2011.
- Wangler, MF, Reiter, LT, Zimm, G, Trimble-Morgan, J, Wu, J, Bier, E. Antioxidant proteins TSA and PAG interact synergistically with Presenilin to modulate Notch signaling in Drosophila. Protein Cell, 2 (7), 554-63, 2011.
- Ferdousy, F, Bodeen, W, Summers, K, Doherty, O, Wright, O, Elsisi, N, Hilliard, G, O'Donnell, JM, Reiter, LT. Drosophila Ube3a regulates monoamine synthesis by increasing GTP cyclohydrolase I activity via a non-ubiquitin ligase mechanism. Neurobiol Dis, 41 (3), 669-77, 2011.
- Urraca, N, Davis, L, Cook, EH, Schanen, NC, Reiter, LT. A single-tube quantitative high-resolution melting curve method for parent-of-origin determination of 15q duplications. Genet Test Mol Biomarkers, 14 (4), 571-6, 2010.
- Allensworth, M, Saha, A, Reiter, LT, Heck, DH. Normal social seeking behavior, hypoactivity and reduced exploratory range in a mouse model of Angelman syndrome. BMC Genet, 12 (1), 7, 2010.
- Doronkin S, Djagaeva I, Nagle ME, Reiter LT, Seagroves TN.. Dose-dependent modulation of HIF-1alpha/sima controls the rate of cell migration and invasion in Drosophila ovary border cells.. Oncogene, 8 (29), 1123-34, 2010.
- Doronkin, S, Reiter, LT. Drosophila orthologues to human disease genes: an update on progress. Prog Nucleic Acid Res Mol Biol, 82, 1-32, 2008.
- Heck, DH, Zhao, Y, Roy, S, LeDoux, MS, Reiter, LT. Analysis of cerebellar function in Ube3a-deficient mice reveals novel genotype-specific behaviors. Hum Mol Genet, 17 (14), 2181-9, 2008.
- Pfleger, CM, Reiter, LT. Recent efforts to model human diseases in vivo in Drosophila. Fly (Austin), 2 (3), 129-32, 2008.
- Reiter, LT, Do, LH, Fischer, MS, Hong, NA, Bier, E. Accentuate the negative: proteome comparisons using the negative proteome database. Fly (Austin), 1 (3), 164-71, 2007.
- Reiter, LT, Seagroves, TN, Bowers, M, Bier, E. Expression of the Rho-GEF Pbl/ECT2 is regulated by the UBE3A E3 ubiquitin ligase. Hum Mol Genet, 15 (18), 2825-35, 2006.
- Reiter, LT, Bier, E. Using Drosophila melanogaster to uncover human disease gene function and potential drug target proteins. Expert Opin Ther Targets, 6 (3), 387-99, 2002.
- Chien, S, Reiter, LT, Bier, E, Gribskov, M. Homophila: human disease gene cognates in Drosophila. Nucleic Acids Res, 30 (1), 149-51, 2002.
- Reiter, LT, Potocki, L, Chien, S, Gribskov, M, Bier, E. A systematic analysis of human disease-associated gene sequences in Drosophila melanogaster. Genome Res, 11 (6), 1114-25, 2001.
- Inoue, K, Dewar, K, Katsanis, N, Reiter, LT, Lander, ES, Devon, KL, Wyman, DW, Lupski, JR, Birren, B. The 1.4-Mb CMT1A duplication/HNPP deletion genomic region reveals unique genome architectural features and provides insights into the recent evolution of new genes. Genome Res, 11 (6), 1018-33, 2001.
- Liehr, T, Reiter, LT, Lupski, JR, Murakami, T, Claussen, U, Rautenstrauss, B. Regional localization of 10 mariner transposon-like ESTs by means of FISH--evidence for a correlation with fragile sites. Mamm Genome, 12 (4), 326-8, 2001.
- Boerkoel, CF, Inoue, K, Reiter, LT, Warner, LE, Lupski, JR. Molecular mechanisms for CMT1A duplication and HNPP deletion. Ann N Y Acad Sci, 883, 22-35, 1999.
- Reiter, LT, Liehr, T, Rautenstrauss, B, Robertson, HM, Lupski, JR. Localization of mariner DNA transposons in the human genome by PRINS. Genome Res, 9 (9), 839-43, 1999.
- Reiter, LT, Hastings, PJ, Nelis, E, De Jonghe, P, Van Broeckhoven, C, Lupski, JR. Human meiotic recombination products revealed by sequencing a hotspot for homologous strand exchange in multiple HNPP deletion patients. Am J Hum Genet, 62 (5), 1023-33, 1998.
- Reiter, LT, Murakami, T, Koeuth, T, Gibbs, RA, Lupski, JR. The human COX10 gene is disrupted during homologous recombination between the 24 kb proximal and distal CMT1A-REPs. Hum Mol Genet, 6 (9), 1595-603, 1997.
- Murakami, T, Reiter, LT, Lupski, JR. Genomic structure and expression of the human heme A:farnesyltransferase (COX10) gene. Genomics, 42 (1), 161-4, 1997.
- Timmerman, V, Rautenstrauss, B, Reiter, LT, Koeuth, T, Löfgren, A, Liehr, T, Nelis, E, Bathke, KD, De Jonghe, P, Grehl, H, Martin, JJ, Lupski, JR, Van Broeckhoven, C. Detection of the CMT1A/HNPP recombination hotspot in unrelated patients of European descent. J Med Genet, 34 (1), 43-9, 1997.
- Murakami, T, Garcia, CA, Reiter, LT, Lupski, JR. Charcot-Marie-Tooth disease and related inherited neuropathies. Medicine (Baltimore), 75 (5), 233-50, 1996.
- Reiter, LT, Murakami, T, Koeuth, T, Pentao, L, Muzny, DM, Gibbs, RA, Lupski, JR. A recombination hotspot responsible for two inherited peripheral neuropathies is located near a mariner transposon-like element. Nat Genet, 12 (3), 288-97, 1996.
- Warner, LE, Reiter, LT, Murakami, T, Lupski, JR. Molecular mechanisms for Charcot-Marie-Tooth disease and related demyelinating peripheral neuropathies. Cold Spring Harb Symp Quant Biol, 61, 659-71, 1996.
- Hubar, JS, Oeschger, MP, Reiter, LT. Effectiveness of radiographic film barrier envelopes. Gen Dent, 42 (5), 406-8, 1994.