Intersection of PARP and ubiquitin signaling in Inflammatory Bowel Disease

Proteins serve essential functions in all living things by performing the many tasks required to keep a cell, and an entire organism, alive and healthy. To perform their jobs properly, however, proteins must be told what to do, and the way that this is accomplished is through protein modifications that serve as microscopic work orders. When proteins are not properly told what to do, this can cause diseases like autoinflammation. Two such modifications, known scientifically as ADP-ribosylation and ubiquitylation, are intimately linked to human health, and accordingly have emerged as multi-billion-dollar therapeutic targets in diseases such as cancer and neurodegeneration. Though historically considered as separate work orders for proteins, we recently discovered that ADP-ribosylation and ubiquitylation function cooperatively through a process we call MARUbylation. Remarkably, we have found that factors controlling MARUbylation are dysregulated in Inflammatory Bowel Disease (IBD). As such, further discovery in this space brings immense potential for understanding and treating these debilitating diseases. Our interdisciplinary team includes world-leaders in ubiquitylation, ADP-ribosylation and intestinal inflammation, bringing together the expertise necessary to understand MARUbylation in IBD. From our proposed work, we expect numerous biological insights and translational discoveries to emerge, yielding transformative impacts on future IBD research and care.