안녕하세요, 데이터사이언스대학원에서 아래의 내용과 같이 BK21 세미나를 개최하오니 여러분의 많은 관심과 참여를 부탁드립니다.
연사 이동원 교수님은 Harvard Medical School의 소아과 조교수이자 Boston Children’s Hospital 신장내과에서 연구원으로 재직 중이시며, Broad Institute of MIT and Harvard의 준회원 및 Harvard Biomedical Informatics 학과의 교수진으로 활동하고 계십니다. 이동원 교수님은 인간 질환, 특히 신장 질환에서의 유전자 조절 메커니즘을 이해하기 위해 단일세포 multi-omics 데이터, 유전체 정보, 머신러닝 기법을 통합하는 연구를 수행하고 있으시며, 임상의 및 실험 생물학자들과 협력하여 예측 결과를 실험적으로 검증하는 데 주력하고 있습니다. 이번 발표에서는 인간 신장에서의 대립유전자 특이적 발현(ASE)을 분석하여, 신장 질환에서 나타나는 유전자 발현 조절의 이상과 그 유전적 원인을 다룬 연구를 소개해주실 예정입니다.
일시: 2025년 4월 29일 오후 2:00 - 3:30
장소: 서울대학교 942동 302호
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.