 |
| Faculty |
|
| Neuroscience Institute |
|
| Neuroscience Seminar Series |
|
| Imaging Center |
|
| Brain Awareness Week |
|
| In The News |
|
| Areas of Research |
|
| Graduate Studies Program |
|
| Students |
|
| Poster |
|
| Links | |
LAWRENCE T. REITER, Ph.D.
Address
Education
Research InterestsMy 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 Rett syndrome (RTT) and Angelman syndrome (AS). These disorders are interrelated at the molecular level and mutations in the gene that causes RTT can also cause 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 or the transcriptional regulator MECP2 may, therefore, account for a significant percentage of inherited autism cases as well. 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 will be validated though genetic suppressor/enhancer screens, immunoprecipitation binding assays in 293T cells and immunohistochemistry in the brains of the appropriate mouse models. We are also performing both proteomic and microarray screens for the transcriptional target genes regulated by the Drosophila MECP2 orthologue, MBD-R2. We will then validate these targets by both indirect (Q_RTPCR) and direct (ChIP) methods in Drosophila tissues. We will then confirm that the mammalian homologues to the targets are also regulated by Mecp2 or Ube3a in the relevant mouse models for Rett syndrome and Angelman syndrome. Our long term hypothesis is that synaptic plasticity in post-mitotic neurons, which requires ubiquitination, is regulated and or executed by the genes transcriptionally repressed by MECP2 and the post translationally modified proteins ubiquitinated by UBE3A. The identification of these target genes may also prove useful in the future since they may be appropriate therapeutic targets for the treatment of autism spectrum disorders. LinksRecent Publications
|