1989 B.S. University of Athens, Greece
1995 Ph.D. University of Athens, Greece
My laboratory is interested in studying the molecular basis of neurodegenerative diseases using Huntington?s Disease (HD) as a model system. HD is an autosomal dominant disorder that affects 1 in 10,000 individuals. HD is characterized by chorea, rigidity and progressive dementia. Symptoms usually begin between the ages of 35 and 50 years, with death typically following 15 to 20 years later. HD is caused by the expansion of an unstable stretch of CAG triplet repeats within the coding region of the HD gene. Moreover the protein encoded by the HD gene, huntingtin, is a novel protein of unknown function.
We are using the mouse as a model organism. Inactivation of the mouse homologue of the HD gene results in embryonic lethality demonstrating that huntingtin is essential for early embryonic development. Conditional inactivation of the gene at later stages results in progressive neurodegeneration in the adult mouse, suggesting that huntingtin is also essential for neuronal survival.
Analysis of genetically engineered mice provides information in the context of the entire organism, throughout development and in adult organs, and complements in vitro analyses of normal and mutant huntingtin. In addition to providing important practical information regarding a devastating disorder, an analysis of the normal function of huntingtin and its interacting proteins can also provide important basic information regarding normal development and neuronal function in the brain.
Molecular Biology: DNA and RNA isolation, PCR, cloning, site-directed mutagenesis,
sequencing, Southern and Northern analysis, RT-PCR analysis, RNase protection,
in vitro transcription.
Biochemistry: SDS-Page, detection of proteins using immunoblotting and immunoprecipitation.
Cell Biology: Cell culture (mammalian cells and in particular fibroblasts
and mouse embryonic stem cells (ES), transfection and electroporation of mammalian
cells, immortalization of cell lines.
Histology: paraffin and frozen sectioning, immunohistochemistry, in-situ
hybridisation, confocal microscopy. Skeleton preparation.
Mouse genetics: Generation of genetically engineered (transgenic, chimeric)
mice. Embryo collection, microinjection and embryo transfer