Therapeutic Intersections of DNA Repair, Immune Signalling, and Epigenetic Control

The Fanconi anaemia DNA repair pathway safeguards genome stability by resolving DNA inter-strand crosslinks and replication stress; its loss promotes NHEJ-mediated genomic instability and leukemic transformation. Beyond haematopoiesis, disrupted DNA damage responses broadly activate innate immune sensing pathways - including cGAS-STING and NF-κB - that rewire epigenetic and transcriptional landscapes. Analogous mechanisms operate across disease contexts: NK cells restrain pulmonary fibrosis by targeting senescent fibroblasts and reprogramming fibroblast lipid metabolism to suppress Hippo-YAP-driven fibrogenesis; Epstein-Barr virus exploits host epigenetic machinery to maintain latency and evade immune elimination; and endothelial epigenetic dysregulation - mediated by long non-coding RNAs such as Malat1 - underlies vascular contributions to cognitive impairment. These parallels suggest that genome integrity, innate immune signalling, and epigenetic regulation form a unified disease-relevant axis.Genomic instability, innate immune activation, and epigenetic reprogramming are increasingly recognized as interconnected drivers of diverse human diseases. This Research Topic addresses a central question: how does disruption of DNA damage repair - particularly the Fanconi anaemia (FA) pathway - interface with downstream innate immune cascades and transcriptional reprogramming to promote oncogenesis and hematologic failure? And how do parallel mechanisms in innate immune cells, viral biology, and vascular physiology converge on similar epigenetic and metabolic axes? By uniting research on FA-pathway-dependent leukemogenesis, NK cell–mediated resolution of pulmonary fibrosis through lipid metabolic reprogramming, epigenetic regulation of Epstein-Barr virus latency, and endothelial epigenetic dysfunction in vascular cognitive impairment, this Topic aims to define shared regulatory logic across disease contexts. The ultimate goal is to leverage these mechanistic insights toward the development of targeted therapies that restore genome integrity, tissue homeostasis, and immune balance.This Research Topic welcomes Original Research, Review, and Mini-Review manuscripts addressing the following themes: (1) FA pathway function in suppressing leukemogenesis, with emphasis on NHEJ-mediated genomic instability, leukemic stem cell biology, and therapeutic targeting in MLL-rearranged or other high-risk leukaemia; (2) NK cell–based immunotherapy in fibrotic disease, including mechanisms of senescent fibroblast elimination, lipid metabolic reprogramming, and Hippo-YAP signalling modulation in IPF and related interstitial lung diseases; (3) epigenetic regulation of herpesvirus (EBV) latency, reactivation, and virus-associated oncogenesis; (4) vascular and endothelial epigenetic mechanisms - including non-coding RNA-mediated regulation - in neuroinflammation and vascular cognitive impairment. Studies employing multi-omics profiling, spatial transcriptomics, mouse disease models, or translational patient cohorts are especially encouraged. Manuscripts bridging two or more of these themes are particularly welcome. Topic editors: Jian Xu, Yuchi Zhang, Yuxin Liu, Rui Wang Source: https://www.frontiersin.org/research-topics/80667/therapeutic-intersections-of-dna-repair-immune-signalling-and-epigenetic-control