Lawrence T. Reiter , Ph.D.

Lawrence T. Reiter , Ph.D.

Associate Professor, Department of Neurology Director, Drosophila Transgenic Core Facility


Education

  • B.S. - University of Southern California, 1991
  • Ph.D. - Baylor College of Medicine, 1997

Post-Graduate Training

  • Fellowship - Drosophila genetics, University of California, San Diego, 2005

Positions and Honors

  • Undergraduate Research - Dr. Carol Miller, U.S.C., Los Angeles, CA, 1987-1991
  • Eighth Grade Teacher - Mc Main School, Orleans Parrish, New Orleans, LA, 1991-1992
  • Research Associate - Dr. Max Oeschger, L.S.U. Dental School, New Orleans, LA, 1992-1993
  • Graduate Student - Dr. James R. Lupski, Baylor College of Medicine, Houston, TX, 1993-1997
  • Postdoctoral Fellow - Dr. James R. Lupski, Baylor College of Medicine, Houston, TX, 1997-1998
  • Postdoctoral Fellow - Dr. Ethan Bier, U.C.S.D., San Diego, CA, 1999-2005
  • Assistant/Associate Professor - Dept. of Neurology, UTHSC, Memphis, TN, 2005-present

Research Interests

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 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.

Representative Publications

L. Reiter and E. Bier. 2002. Using Drosophila melanogaster to uncover human disease gene function and potential drug target proteins. Expert Opinion on Therapeutic Targets. 6:387-399.

S. Chien, L. Reiter, E. Bier and M. Gribskov. 2002. Homophila: human disease gene congnates in Drosophila.Nucleic Acids Research 30:149-51.

K. Inoue, K. Dewar, N. Katsanis, L. Reiter, E. Lander, K. Devon, D. Wyman, J. Lupski and B. Birren. 2001. The 1.4-Mb CMT1A duplication/HNPP deletion genomic region reveals unique genome architectrual features and provides insights into the recent evolution of new genes. Genome Research11:1018-1033.

L. Reiter, L. Potocki, M. Gribskov and E. Bier. 2001. A systematic analysis of human disease associated gene sequences in Drosophilamelangaster. Genome Research11:1114-1125.

T. Liehr, L. Reiter, J. Lupski, T. Murakami, U. Cluassen and B. Rautenstrauss. 2001. Regional localization of 10 mariner transposon-like ESTs by means of FISH-evidence for a correlation with fragile sites. Mammalian Genome 12:326-328.

L. Reiter , T. Liehr, B. Rautenstrauss, H. Robertson and J. Lupski. 1999. Human recomination-associated genomic disorders appear to coincide with locations of mariner transposons. Genome Research 9:839-843.

L . Reiter , E. Nelis, P. De Jonhge, C. Van Broekhoven and J. Lupski. 1998. Human meiotic recombination products revealed by sequencing a hotspot for homologous strand exchange in multiple HNPP deletion patients. American Journal of Human Genetics62:1023-1033.

V. Timmerman, B. Rautenstrauss, L. Reiter, T. Koeuth, A. Löfgren, T. Leihr, E. Nelis, K. Bathke, P. De Jonghe, H. Grehl, J.- J. Martin, J. Lupski and C. Van Broeckhoven. 1997. Detection of the CMT1A/HNPP recombination "hotspot" in unrelated patients of European descent. Journal of Medical Genetics34:43-49.

T. Murakami, L. Reiter and J. Lupski. 1997. Genomic structure and expression of the human heme A:farnesyltransferase (COX10) gene. Genomics 42:161-164.

L. Reiter , T. Murakami, T. Koeuth, R. Gibbs and J. Lupski. 1997. The human COX10 gene is disrupted during homologous recombination between the 24-Kb proximal and distal CMT1A-REPs. Human Molecular Genetics 6:1595-1603.

L. Reiter , T. Murakami, T. Koeuth, L. Pentao, M. Muzny, R. Gibbs and J. Lupski. 1996. A recombination hotspot responsible for two inherited peripheral neuropathies is located near a mariner transposon-like element. Nature Genetics12:288-297.

L. Reiter , D. Steffen, S. Shapira, J. Lupski, M. Frazier and D. Wheeler. 1995. A searchable video database of dysmorphology. Journal of the American Medical Informatics Association (symposium supplement SCAMC Proceedings), p. 1000.

J. Hubar, M. Oeschger and L. Reiter. 1994. Effectiveness of radiographic film barrier envelopes. General Dentistry 42:406-408

Contact Us

Department of Neurology

415 Link Building
855 Monroe Avenue
Memphis, Tennessee 38163
Phone: (901) 448-6199
Fax: (901) 448-7440

David M. Stern, M.D.
Executive Dean

Andrei V. Alexandrov, M.D.
Chairman, Department of Neurology
Semmes-Murphey Professor
aalexa30@uthsc.edu