Research in the Nguyen Lab
Our lab is interested in studying the roles of repetitive DNA or “genome dark matter” in disease and cellular function. We use molecular, genetic, and advanced sequencing and computational tools, animal models, patient samples and patient-derived models to identify and study pathogenic or functional tandem repeats and repeat expansions.
Our research aims to:
- Identify novel repeat expansions that contribute to Alzheimer’s disease (AD), amyotrophic lateral sclerosis (ALS), and other neurological disorders
- Study how novel repeat expansion mutations contribute to these diseases and the involvement of stress in triggering and exacerbating disease
- Study if and how tandem repeats regulate gene expression & function of the central nervous system (CNS)
We believe our research will lead to identification of novel therapeutic targets, development of disease models, and treatment strategies for neurodegenerative and neurological disorders.
- Alzheimer’s disease (AD)
- Amyotrophic lateral sclerosis (ALS)
- Frontotemporal dementia (FTD)
- Other neurodegenerative and neurological diseases with unknown etiologies
Who we are and what drives our research?
We are a group of scientists who are highly enthusiastic about learning new things about human genetics, the central nervous system, and related diseases.
As so, we love new ideas, asking questions, and creating new molecular biology tools.
We very much care about patients and we wish to contribute to helping patients.
We are looking for outstanding and motivated students, postdocs, and biological scientists to join our team. Please contact Dr. Nguyen for details on open positions.
Lien has always been interested in understanding the molecular pathogenesis of neurodegenerative disorders and in developing therapeutic strategies for these devastating diseases. She received her B.S. in Chemistry from Hanoi College of Science at Vietnam National University. Dr. Nguyen then earned her Ph.D. in Chemistry at the University of Illinois at Urbana-Champaign with Dr. Steven Zimmerman, in which she designed, synthesized, and studied biological activities of small molecules that target Myotonic Dystrophy. Continuing her interest in repeat expansion disorders, she joined the lab led by Dr. Laura Ranum in the Center for NeuroGenetics (CNG) as a postdoctoral fellow. During the early phase of the postdoctoral training, Lien studied the roles of C9orf72 repeat-associated non-AUG (RAN) proteins in disease pathogenesis and developed therapeutic strategies for C9orf72 ALS/FTD.
While doing research in repeat expansion disorders, Lien learned that the discovery of repeat expansion mutations is very challenging because of technical difficulties. Since repetitive elements account for >50% of human genome, it is highly likely that many repeat expansion mutations remain unidentified and could contribute to common disorders including Alzheimer’s disease (AD). This innovative thought has led Lien to develop a novel pathology-to-gene-identification strategy to isolate and study the roles repeat expansion mutations in disease with unknown genetic etiologies. In 2020, Lien received the K99/R00 – Pathway to Independence Award (NIH/NIA) to develop and use this strategy to study genetics and molecular mechanisms of AD. In December 2022, Lien started her independent lab in the CNG, the Department of Molecular Genetics and Microbiology, University of Florida. She is enthusiastic about gaining new knowledge and doing research to increase our understanding of disease and how the central nervous system works. She looks forward to working with outstanding and motivated researchers and to contributing to the huge effort of the scientific community to help patients and their families.
Research in the Nguyen Lab
Our research focuses on three main areas: 1) detecting novel tandem repeats and repeat expansions (RE), 2) studying the pathogenic roles of novel RE mutations, and 3) studying functions of tandem repeats in the CNS.
1) Repeat expansion detection
We screen repeat expansion related pathology including the accumulation of RAN proteins and RNA foci in patient tissue and samples to identify cases that could carry novel RE mutations. We then use this information 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.
2) Pathogenic roles of novel RE mutations
We develop animal models (AAV, BAC transgenic, and knock-in) and patient-derived models (2D and 3D) 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.
3) 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.