Leveraging new knowledge from the human pancreas to advance and improve understanding and treatment of Type 1 diabetes

Type 1 diabetes (T1D) affects >413,000 people in the UK, with incidence increasing 4% annually. Despite significant improvements in care and management, reliance is still placed on insulin replacement as a primary mode of therapy rather than on strategies to arrest or reverse disease progression, or efforts to replace functional beta cells. Progress will only be possible with a more comprehensive understanding of disease processes in the target organ, the pancreas, which is difficult in situ. This current proposal builds on my experience and track record, and my access to rare pancreas biobanks, to explore new avenues which will lead directly to patient benefit. It will focus on: defining differences between individuals to better define distinct forms of T1D (WP1; Fig1); exploring strategies that beta cells use to resist immune attack (WP1/2); engaging with, and contributing to, global T1D research networks seeking to validate key immunotherapeutic targets (WP3). It will use state-of-the-art imaging platforms allowing detailed interrogation of pancreas tissue from global biobanks, coupled with in vitro model systems involving co-culture of beta cells and immune cells. The outcomes will guide treatment and prevention strategies and offer valuable translational insights to inform the development of beta-cell recovery and replacement approaches.