Analysis of biological processes affected in individuals carrying genetic mutations associated with autism spectrum disorders.
- Study of autism and neurodevelopmental problems associated with abnormal amino acid (AA) homeostasis. Individuals with mutations in genes regulating the levels of branched-chain amino acids e.g. BCKDK or SLC7A5 show autism-associated behaviors, motor issues and microcephaly. SLC7A5 encodes a large neutral amino acid transporter called LAT1, which is responsible for regulating the branched-chain amino acid homeostasis in the brain. Employing a series of mouse models we discovered that a reduction of branched-chain amino acid (i.e. valine, leucine and isoleucine) levels leads to abnormal protein synthesis in the brain and several neurological abnormalities. Currently, we are studying how mutations in BCKDK or SLC7A5, and the consequent reduction in AA levels lead to specific neurodevelopmental defects.
- Study of mutations in genes encoding chromatin associated/modifier proteins. Several individuals with mutations in chromatin modifier genes have autism associated features, intellectual disability and developmental issues. Employing a series of in vivo and in vitro models we are studying how mutations in these genes affect brain development and function.
Our research won an ERC award and is funded by the European Research council.
Convergent molecular pathways in autism.
Although seemingly diverse, genes involved in autism spectrum disorders (ASDs) seem to converge along specific biological pathways. We hypothesize that the direct results of convergent network perturbations should be observable as measurable changes in the cerebral tissue. Thus, employ comparative analyses and system biology approaches to identify key molecular changes underlying ASDs.
The development of the nervous system is characterized by several phases that occur in a precise sequence. The correct temporal sequence and duration of each developmental phase is finely regulated and essential to obtain a properly functioning brain. ASDs have been classified as neurodevelopmental conditions. Due to their developmental nature, ASDs have typically been thought of as possibly preventable but not curable if the intervention was to be initiated once development has been completed, and thus to be a group of irreversible disorders. We are exploring how and when autism features are reversible at adult stages.