Le Pen Lab
My research seeks to explain a fundamental paradox in human disease: why common viral infections cause little harm in most individuals yet lead to life-threatening or chronic disease in others. We investigate the cell-intrinsic mechanisms of innate immunity that enable cells to detect viruses, limit infection, and resolve immune activation after the pathogen has been cleared. Our work has revealed that these fundamental pathways can determine the outcome of infection, shaping both antiviral defense and inflammatory pathology.
651 Huntington Avenue,
Building FXB, Room 205
Boston, MA 02115
Innate Immunity to RNA Viruses
Most viral infections are rapidly controlled and eliminated by the body’s natural defenses, leaving little lasting consequence. However, when the body’s immune response fails to effectively control an infection or shut down once the threat has passed, it can contribute to disease. In some cases, this leads to severe illness during the infection itself. In others, inflammation – a cellular state that helps limit infection but can also interfere with normal cellular and tissue function -persists long after the virus has been eliminated, causing chronic disease that can last for months or years.
Our laboratory studies how cells balance antiviral defense with the preservation of normal cellular function. We focus on long-lived, irreplaceable cell types such as neurons and pancreatic β cells, whose loss cannot be readily compensated by tissue regeneration. Unlike epithelial cells that can be continuously replaced, these cells must survive infection while maintaining the specialized functions on which the body depends. We hypothesize that this challenge requires dedicated mechanisms that allow antiviral responses to be mounted, controlled, and ultimately terminated without compromising cellular identity and function.
To understand these mechanisms, we investigate three fundamental questions. First, how do cells distinguish their own RNA from that of invading viruses and initiate an appropriate immune response? Second, how do infected cells control viral replication while preserving the specialized functions required for normal tissue function? Third, how are antiviral and inflammatory responses actively shut down once a threat has been eliminated? By answering these questions, we seek to define how failures in viral sensing, virus control, and inflammatory resolution contribute to acute disease, chronic inflammation, and tissue dysfunction.
