Di Virgilio Lab

Our Research

How do cells preserve genome integrity while executing specialized biological functions?

Our laboratory investigates the molecular mechanisms that preserve genome integrity during both physiologically programmed and pathological DNA damage. By combining DNA repair, chromatin biology, and immunology, we seek to understand how genome maintenance pathways are regulated, how they are adapted to different biological contexts, and how their dysfunction contributes to human disease.

For many years, our research has focused on B lymphocytes, a unique cellular system in which programmed DNA damage is deliberately generated to diversify antibody responses while preserving genome stability. This balance between genome diversification and genome integrity provides a powerful framework to uncover fundamental principles of DNA repair regulation.

Building on these foundations, we are extending our research beyond the immune system to investigate how genome maintenance pathways operate in different cellular contexts and how variation in genome maintenance strategies contributes to disease susceptibility, tissue vulnerability, and biological resilience.

DNA Repair and Genome Maintenance in B Cells: Physiology and Disease

B lymphocytes provide a unique physiological system in which programmed DNA damage is deliberately generated to diversify antibody responses. For over a decade, our laboratory has investigated how mature B cells safely generate, process, and repair this programmed DNA damage while preserving genome integrity during immune responses.

Through the study of antibody diversification, we have uncovered molecular mechanisms controlling DNA end protection, chromatin regulation, transcriptional control, cellular stress responses, and the coordination of DNA repair with B‑cell differentiation. Building on these discoveries, we are now investigating how DNA repair pathways are integrated with the broader biology of activated B lymphocytes, how genome maintenance is coordinated with cellular state, transcriptional programs, and immune function, and how defects in these processes contribute to immunodeficiency, lymphomagenesis, and other disorders of adaptive immunity.

By studying programmed DNA damage in B lymphocytes, we seek to uncover general principles of genome maintenance that extend far beyond the immune system.

Genome Maintenance Across Biological Systems: Vulnerability and Resilience

Defects in genome maintenance pathways are associated with a remarkably broad spectrum of human disorders, including immunodeficiency, cancer predisposition, developmental abnormalities, and neurological disease. Understanding why these defects manifest so differently across cell types and tissues remains one of the major unanswered questions in genome stability research.

Building on our expertise in the molecular mechanisms of DNA repair, we are establishing a complementary research program that extends these studies beyond the immune system. Our current efforts focus on developing neuronal and human iPSC-based models to investigate how genome maintenance pathways are adapted to different biological contexts and to understand the cellular mechanisms that determine vulnerability or resilience to genome instability.

More broadly, we seek to understand how genome maintenance strategies vary across cell types, tissues, and biological systems, and how these differences influence physiology, disease susceptibility, and organismal resilience. By integrating mechanistic studies with emerging cellular models, we aim to uncover both universal and context-dependent principles that govern the preservation of genome integrity throughout life.