Back to Top
Charles H. Hood Foundation | Eunjung Alice Lee, Ph.D. – July 2019
By identifying innovative pediatric advancements and providing funding in the critical phases of development, we are able to expedite high-impact breakthroughs that improve the health and lives of millions.
portfolio_page-template-default,single,single-portfolio_page,postid-17770,ajax_fade,page_not_loaded,,qode-title-hidden,qode-child-theme-ver-1.0.0,qode-theme-ver-10.0,wpb-js-composer js-comp-ver-4.12,vc_responsive

Eunjung Alice Lee, Ph.D.

Assistant Professor

Boston Children’s Hospital

Systematic Discovery and Correction of Splicing Defects caused by Retroelement Insertions


Key Words: Splicing, Transposable elements, Retrotransposon, Antisense oligonucleotides (ASOs), Genetic disease

The objectives of this proposal are to systematically uncover transposable element (TE) insertions as an under-explored genetic cause of childhood Mendelian diseases (Aim 1) and to characterize how the insertions influence RNA splicing and screen antisense-oligonucleotides (ASO) to correct splicing defects (Aim 2). This project will therefore be supportive of our long-term goal of defining the role of TE insertions in diverse human diseases beyond Mendelian diseases and provide the basis for effective diagnosis and treatment.

My laboratory focuses on aberrations in repetitive DNA, particularly transposable elements, and how they affect RNA in various human diseases, including cancer, Mendelian disorders, and complex neurological disorders. My expertise is in large-scale genomic and transcriptomic analysis of human TEs and splicing. In this proposal, we will analyze genome sequences from multiple rare childhood disease cohorts using Tea (Transposable Element Analyzer), a computational method I have developed to identify TE insertions at single-nucleotide resolution (Science 2012; Neuron 2015).

As numerous studies, including our own, indicate that TE insertions greatly influence gene transcripts, we will perform RNA-seq analysis on selected candidates to understand these insertional effects. For TE insertions that are confirmed as splice-altering, we will design and screen ASOs to restore normal splicing. Our preliminary data demonstrates the feasibility of splicing modulation therapy and has yielded high quality insertion candidates to justify this line of investigation.

Given that genetic causes of a significant fraction of cases with Mendelian disorders remain unresolved with conventional single-nucleotide variant analysis, we expect our focused and systematic investigation to provide insights into the relevance and importance of TE insertions as a previously underappreciated mechanism at work in Mendelian disorders as well as providing a foundation for effective diagnosis and novel therapeutics to greatly improve childhood health.