NLM DIR Seminar Schedule

Abstract:

Cell identity and disease states are shaped by transcription factor (TF) activity within cis-regulatory landscapes organized in three-dimensional chromatin space. Regulatory element composition and spatial organization are highly dynamic and frequently disrupted in cancer. The Abraham lab develops computational approaches to identify cis-regulatory architectures governing cell identity and their aberrant activation in pediatric malignancies. Using graph-based machine learning, we define higher-order communities of cis-regulatory elements, termed “3D super-enhancers,” that coordinate long-range gene regulation and association with transcriptional condensates. We also examine early enhancer and TF activation events during rhabdomyosarcoma transformation, revealing coordinate activation of muscle and neural lineage programs preceding overt oncogenic states and underscoring fundamental principles of gene dysregulation in cancer.