Since many FA patients also suffer from diabetes and insulin resistance, the research proposed in this application is designed to determine the function of Fanconi anemia proteins in the endocrine pancreas. This study will analyze the dynamic features of FA protein expression and response to glucose in purified human islets from donors and evaluate impaired expression on hormone secretion. Additionally, a comprehensive quantitative proteomics analysis of FA interacting proteins by mass spectrometry will delineate the “normal” molecular pathways by which FA proteins prevent diabetes and insulin resistance. Understanding these alternative pathways could lead to precision treatments in FA patients that help prevent or treat these endocrinopathies with the goals of diminishing adverse responses to hematopoietic cell transplant and improving their lives. Research my lead to new treatments for diabetes in both the FA and general population.