Neuroscience Institute

• News & Events
  • Grants (New and Support)
  • Faculty Spotlight
  • Seminars
  • Symposia
  • Brain Awareness Week
• Departments
• Graduate Program
• Fellowship Information
  (Mentors & Undergraduates)
• Faculty Directory
• Conference Room
  (Schedule / Reservations)
• Imaging Center
• Resources
  (Behavioral Core & Mouse Lines)
• Links

Education

• Ph.D. Institution: Department of Cell and Molecular Biology, Baylor College of Medicine
• Postdoctoral: University of California San Diego

Links

• Tooth Study
• Homophila Database
• Negative Proteome Database
• Duplication 15q Alliance
• GoogleScholar H-Index

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 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, cause fragile X, RTT or AS. 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 40 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.

Representative Publications

• 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. 2011 Dec 12;2(1):19. PubMed PMID: 22152151; PubMed Central PMCID: PMC3287113.
• 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. 2011 Dec;125(6):962-9. Epub 2011 Oct 17. PubMed PMID: 22004265.
• 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. 2011 Jul;2(7):554-63. Epub 2011 Aug 6. PubMed PMID: 21822800.
• 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. 2011 Jan 14;12:7. PubMed PMID: 21235769; PubMed Central PMCID: PMC3025901.
• 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. 2011 Mar;41(3):669-77. Epub 2010 Dec 13. PubMed PMID: 21147225; PubMed Central PMCID: PMC3040417.
• Urraca N, Davis L, Cook EH Jr, 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. 2010 Aug;14(4):571-6. PubMed PMID: 20642357; PubMed Central PMCID: PMC3064527.

View more references (pubmed link)