Research Overview

The Lee laboratory studies transposable elements and other types of genomic variations in human disease using computational genomic and bioinformatic approaches. Specifically, we develop and apply computational methods for genomic studies using next-generation sequencing and perform integrative analyses of DNA- and RNA-sequencing data.

Laboratory Projects

  1. Pathogenic retrotransposon insertions in human disease: Retrotransposon mobilization is a significant source of human genomic variability and is causally implicated in various Mendelian disorders and complex diseases. We aim to define the relevance and importance of retrotransposon insertions as a mechanism underlying human diseases, including cancer, Mendelian disorders, and complex neurological disorders.
  2. The role of somatic mutation in developmental and degenerative disorders: Our previous single-cell studies have revealed extensive somatic mosaicism in the human brain. We aim to analyze single-cell genomic data and develop novel methods to detect various types of low-clonal or single-cell unique somatic mutations and to understand how these mutations relate to neurodegeneration.
  3. The effects of DNA variants on RNA splicing: One major pathogenic mechanism underlying human disease is disruption of RNA splicing caused by DNA mutations including retrotransposon insertions. Our recent analysis of cancer DNA- and RNA-seq profiles found a large set of somatic mutations that disrupted RNA splicing, highlighting intron retention as a common yet underappreciated mechanism of tumor suppressor inactivation. Our goal is to systematically characterize the effects of pathogenic DNA variants, especially non-coding variants, on RNA splicing.

About E. Alice Lee

Dr. Lee received her BA and MS in Computer Science, and her PhD in Bioinformatics from the Korea Advanced Institute of Science and Technology (KAIST) in South Korea. During her PhD, she studied pathway and network analysis as a research associate in Dr. Trey Ideker's laboratory at UC, San Diego. She served as a postdoctoral fellow in Peter Park’s laboratory at Harvard Medical School (HMS) starting in 2010 and became an Instructor in 2013. She joined the faculty in the Division of Genetics and Genomics at Boston Children's Hospital in 2017 and is currently an Assistant Professor of Pediatrics at HMS. She won an NIH K01 award for work on somatic mutations in neurodegenerative disorders, and

Selected Publications

Lee E, Iskow R, Yang L, Gokcumen O, Haseley P, Luquette LJ, Lohr JG, Harris CC, Ding L, Wilson RK, Wheeler DA, Gibbs RA, Kucherlapati R, Lee C, Kharchenko PV**, Park PJ**, and The Cancer Genome Atlas Research Network (2012) Landscape of somatic retrotransposition in human cancers, Science, 337:967-71. PMCID: PMC3656569

Evrony GD*, Lee E*, Mehta BK, Benjamini Y, Johnson RM, Cai X, Yang L, Haseley P, Lehmann HS, Park PJ**, Walsh CA** (2015) Cell lineage analysis in human brain using endogenous retroelements. Neuron, 85:49-59.

Jung H, Lee D, Lee J, Park D, Kim YJ, Park W, Hong D**, Park PJ**, Lee E** (2015) Intron retention is a widespread mechanism of tumor suppressor inactivation, Nature Genetics, Nov;47(11):1242-8 PMID: 26437032

Evrony GD*, Lee E*, Park PJ**, Walsh CA** (2016), Resolving Rates of Mutation in the Brain using Single-Neuron Genomics, eLife,5. pii: e12966 PMID: 26901440

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