Research | Jeong Lab

Our lab studies how genome structure and epigenetic regulation evolve, and how that variation contributes to differences in species, cell types, aging, and disease risk. We combine comparative genomics, long-read sequencing and telomere-to-telomere assemblies, DNA methylation profiling, and single-cell and multi-omic approaches to identify the genetic and evolutionary origins of regulatory variation and its effects on gene expression and genome function. By comparing humans and other non-human primates, we ask what makes the human genome distinct and how human-derived genetic and regulatory changes contribute to human traits and disease susceptibility.

Comparative Neurogenomics

Comparative DNA methylation patterns across human and non-human primate brain cell types — Comparative epigenomic analyses reveal human-derived DNA methylation patterns across primate brain cell types and connect lineage-specific regulatory changes to genes and pathways involved in neurodevelopment.

We study how DNA methylation changed along the human lineage, with a focus on the brain and neurodevelopment. By comparing humans with non-human primates, we identify methylation patterns that evolved during human evolution. Our work examines these changes in cell-type-level, including neurons and glial cells, and asks how they are associated with transcriptional programs and neurodevelopmental pathways. We also develop computational methods for comparative neurogenomics and epigenomics, enabling us to distinguish lineage-specific methylation changes from cell type composition, technical variation, and species-specific genome annotation differences.

Complex Genome Architecture and Duplicate Genes

Chromosome alignment of chromosome 16 between human and chimpanzee assemblies. The aligned region (blue) includes multiple large inversion (orange) and translocation events. Large structural variation between species is flanked by segmental duplications (red) and overlaps genomic regions associated with a copy number variation morbidity map of developmental delay (turquoise).

Segmental duplications, copy number variable regions, and large structural variants are among the most dynamic parts of the genome. They often contain duplicated genes and regulatory elements that evolve rapidly, but they are difficult to analyze because highly similar paralog copies cannot be assigned to their original genomic locations with short-read sequencing. Our lab uses long-read sequencing, telomere-to-telomere genome assemblies, and donor-derived genome assemblies to separate gene copies, reconstruct structurally complex loci, and measure paralog-specific epigenomic patterns. By integrating DNA methylation with multi-tissue epigenome data, we study how duplicated genes acquire distinct regulatory states during human evolution and how these changes influence neurodevelopmental gene regulation and tissue-specific genome function.

Epigenetic Aging and Cell Identity

Cell-resolved DNA methylation profiles across species, ages, and disease contexts — Cell-resolved DNA methylation profiling reveals how regulatory states vary across cell types, species, ages, and disease contexts. These maps support mechanistic studies of epigenomic remodeling during tissue aging, injury response, and disease-associated repair.

We study how DNA methylation changes during aging and how these changes differ across cell types, tissues, species, and disease states. Aging can alter cell type-specific methylation patterns, disrupt regulatory programs that maintain cell type identity, and shift cells toward injury-associated or disease-associated states. Our lab uses single-cell DNA methylation profiling, cross-species comparisons, transcriptomics, chromatin accessibility, and spatial genomics to map these age-associated changes in defined cell populations. By comparing aging trajectories across tissues and species, we aim to identify which epigenomic changes are conserved, which are human-specific, and how they contribute to vulnerability in the brain and other organs.