Hello,
The Graduate School of Data Science is pleased to host the BK21 Seminar as detailed below, and we invite your active interest and participation.
Professor Dongwon Lee is an Assistant Professor of Pediatrics at Harvard Medical School and a researcher in the Division of Nephrology at Boston Children’s Hospital. He also serves as an Associate Member of the Broad Institute of MIT and Harvard and as part of the faculty at Harvard Biomedical Informatics. His research focuses on integrating single-cell multi-omics data, genomic information, and machine learning techniques to understand gene regulatory mechanisms in human diseases, particularly kidney diseases. Professor Lee collaborates with clinicians and experimental biologists to experimentally validate predictive findings.
In this presentation, he will introduce his research analyzing Allele-Specific Expression (ASE) in the human kidney, addressing abnormalities in gene expression regulation observed in kidney diseases and their genetic causes.
Date and Time: April 29, 2025, 2:00 PM - 3:30 PM
Location: Room 302, Building 942, Seoul National University
Speaker: Dongwon Lee
Title: The landscape of allele-specific expression in human kidneys in health and disease
Abstract:
Allele-specific expression (ASE), the preferential expression of one gene copy, is a fundamental gene regulatory mechanism in pathogenesis across human tissues. While ASE has been observed in the kidney, comprehensive assessments remain limited. Here, we present a high-quality, genome-wide ASE map of microdissected glomerular and tubulointerstitial compartments from human kidneys. We leveraged a unique dataset of paired whole-genome sequencing and bulk RNA-seq, analyzed with improved computational pipelines for ASE analyses incorporating advanced bias correction. Our analysis reveals a higher proportion of genes exhibiting ASE in glomerular compartments compared to tubulointerstitial compartments in proteinuric kidneys, but not in healthy kidneys. Integration with single-cell RNA-seq data identifies cell-type specific expression of many ASE genes. We then characterize genomic mechanisms driving ASE in our cohort, including cis-regulatory variants, alternative splicing, and imprinting. Furthermore, differential gene expression analysis revealed that overexpression of genes in glomeruli with high ASE proportion were involved in fundamental processes such as mitochondrial function, ATP production, ribosome biogenesis, and cytoplasmic translation, suggesting a link between ASE genes and these core cellular mechanisms in disease. Finally, we employ an ASE-based approach to characterize kidney-specific imprinting patterns, identifying novel candidate imprinted genes. This study provides a comprehensive landscape of ASE in the human kidney, highlighting transcriptional dysregulation in proteinuric disease and revealing key cellular drivers and genetic determinants.
Bio:
Dongwon Lee is an assistant professor of Pediatrics at Harvard Medical School and a research associate at Boston Children’s Hospital. He is also an associate member of the Broad Institute of MIT and Harvard. His research focuses on the role of gene regulation in human diseases, particularly kidney diseases, through integrative analysis of single-cell multiomics, genetic data, and machine learning. He works closely with clinicians and experimental biologists to validate computational predictions. He received his Ph.D. in Biomedical Engineering from Johns Hopkins University under the supervision of Michael Beer, and his B.S. in Computer Science and Biological Sciences from KAIST. Prior to joining Harvard, he conducted postdoctoral research at Johns Hopkins and NYU with Professor Aravinda Chakravarti.