Three main areas we focus on:
1) Detecting novel tandem repeats and repeat expansions
2) Studying the pathogenic roles of novel repeat expansion mutations
3) Studying functions of tandem repeats in the central nervous system (CNS)
Alzheimer’s disease (AD)
Amyotrophic lateral sclerosis (ALS)
Frontotemporal dementia (FTD)
Other neurodegenerative and neurological diseases with unknown etiologies
We believe our research will lead to identification of novel therapeutic targets, development of disease models, and treatment strategies for neurodegenerative and neurological disorders.
Repeat expansion detection
We screen repeat expansion related pathology (e.g. the accumulation of RAN proteins and RNA foci) in patient tissue and samples to identify cases that could carry novel repeat expansion mutations.
We then use the information of repeat expansion pathology for enrichment and detection of repeat expansions in patient individuals at genome-wide scales.
Case control association studies are performed to identify novel disease-associated repeat expansion mutations.
Repeat expansion in disease
We develop animal models (AAV, BAC transgenic, and knock-in) and patient-derived models (e.g. 2D cell cultures and 3D organoids) that express novel disease-associated RE mutations. These models combined with patient samples are used to study the contribution of the novel repeat expansions in disease. Additionally, these models are important tools that allow us to test the effects of stress in triggering or exacerbating disease and that could contribute to development of personalized medicine.
Tandem repeats in the CNS
Understanding the functions of tandem repeats and repeat expansions in biology can provide important information for developing therapeutic interventions and methods to regulate cellular function. Here we test the hypothesis that tandem repeats are an important player in maintaining the CNS function by regulating expression of CNS-specific genes and involving in response to stress. We use transcriptomic data, sequencing and bioinformatic tools, gene editing and reporter assays to tackle this question.