Kathleen E. DelGiorno, PhD

Overview

Pancreatic cancer is now the third leading cause of cancer death. This illustrates the dire need for new, better diagnostics, which, in turn, requires a better understanding of initiating events in tumor progression. We have found that early, pre-cancerous lesions have substantially more cellular heterogeneity than once thought, including a significant population of tuft cells. Tuft cells are solitary chemosensory cells found throughout the hollow organs of the digestive tract. They express components of taste, inflammatory, and neuronal cell signaling and we have found that they form spontaneously in the pancreas with chronic injury or oncogenic mutation. The limited functional data available from the study of other systems suggests that these cells have the ability to sense intra-luminal content and may instruct immune and nerve cells to control local secretory and absorptive processes. Using novel genetically engineered mouse models we have found that tuft cells have the potential to instruct several different cell populations. We hypothesize that tuft cells modulate the immune system and that elimination induces an inflammatory reaction resulting in prolonged pancreatic injury and increased risk of cancer. The scientific objective of this proposal is to expand our functional data to establish if targeting or bolstering tuft cells confers therapeutic benefit. The prevalence of tuft cells in pancreatic disease and the lack of functional data make this a meaningful and important area of study. Successful completion of these aims will enhance our understanding of pancreatic disease initiation and progression.