Yu-Ju Chen is a neuroscientist who studies the molecular and cellular mechanisms of pathophysiology underlying neurodevelopmental disorders. He has a doctorate in biomedical science. After completing Ph.D. training in Guo-Jen Huang’s laboratory at Chang Gung University in Taiwan, he joined Hye Young Lee’s laboratory at the University of Texas Health Science Center at San Antonio as a postdoctoral research fellow in 2022. He focuses on the following areas of research: 1) identifying the molecular and cellular mechanisms responsible for the pathophysiology underlying fragile X syndrome, and 2) using non-viral vector to deliver Cas9 mRNA/sgRNA to develop potential therapeutics in mouse models for brain disorders. To address these questions, he uses molecular and cellular neurobiology tools, bioengineering and animal behavioral assays.

Principal Investigator: Hye Young Lee

Fellow: Benjamin Fletcher

Undergraduate Fellow Project: Non-viral gene editing in brain disorders

Gene therapeutics have great potential for treating neurological disorders. However, challenges with delivery have limited their clinical potential. CRISPR/Cas9 is one of the most widely used gene editing tools due to the target specificity and simple design of sgRNA lending it both precision and ease of use. The Lee Lab has demonstrated that gene editing with Cas9 RNPs (Cas9 protein/sgRNA complexes) using non-viral delivery is possible in adult mouse brain (see Lee et al.2018, Nature Biomedical Engineering). Our current project aims to deliver Cas9 in a form of mRNA/sgRNA using non-viral vector in brain disorder mouse models given the promising features of mRNA delivery. To achieve this goal, aim 1 will focus on identifying the most efficient delivery vehicle by using reporter mice which can detect tdTomato expression as a result of gene editing. Aim 2 will focus on optimizing a dose, brain region, delivery efficiency, injection method and duration conditions. Aim 3 will focus on testing delivery vehicle in the preclinical model for brain disorders. We will use molecular, cellular and behavioral assessments to test aim 3.