Research
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Gene Dosage and Cell-Type-Specific Regulation of Brain Development and Dysfunction
We study why a 50% change in the copy number of a single transcriptional regulator — retinoic acid-induced 1 (RAI1) or TCF20 — produces such diverse and severe neurodevelopmental consequences. Our work reveals that dosage-sensitive transcriptional regulators do not cause a single, uniform phenotype; instead, they program distinct circuit properties in different cell types, at different developmental windows and in diverse brain regions. By dissecting these cell-type- and region-specific mechanisms in mice and in human iPSC-derived neurons, and by developing gene- and circuit-targeted interventions, we work toward therapies for Smith-Magenis syndrome, Potocki-Lupski syndrome, and TCF20-associated neurodevelopmental disorder — three conditions caused by disruption of the same transcriptional complex. Currently, we are interested in the following questions:
Molecular and Cellular Pathogenic Mechanisms of Syndromic Autism Spectrum Disorders:
Molecular and Cellular Pathogenic Mechanisms of Syndromic Autism Spectrum Disorders:
- How does gene dosage imbalance affect molecular and cellular aspects of neuronal development and function?
- What are the neurobehavioural and neural circuit functions of RAI1-containing chromatin complex?
- Building novel disease models of syndromic autism spectrum disorders
- How to correct disrupted molecular signalling pathways and reverse symptoms of syndromic autism spectrum disorders?
- Can increasing the expression levels of disease-causing genes at transcriptional and post-translational levels alleviate disease features?
For our published work, please visit the PUBLICATIONS page