Tuft Cell–Derived Prostaglandin D2 as a Target for Chemoprevention in FAP
Ken S. Lau, PhD
Professor of Cell and Developmental Biology
Director of the Center for Computational Systems Biology
Vanderbilt University School of Medicine
Tuft Cell–Derived Prostaglandin D2 as a Target for Chemoprevention in FAP
Chronic baseline inflammation and the resulting tissue damage are major risk factors for the development of precancerous lesions, particularly in individuals with Familial Adenomatous Polyposis (FAP), which is a hereditary disorder that predisposes the gastrointestinal tract to the formation of precancerous polyps. Thus, strategies that reduce inflammation prior to polyp formation represent an attractive chemoprevention approach for FAP. This pilot project focuses on tuft cells, a rare epithelial cell type in the gut that senses the microbiome and modulates immune responses. Tuft cells have been previously shown to suppress inflammation in models of inflammatory bowel disease. Specifically, we will investigate the function of prostaglandin D2 (PGD2), an immunomodulatory molecule that is produced uniquely by tuft cells in the gut. In this pilot, we will first use models of FAP to track tuft cell behaviors and PGD2 production throughout the course of disease. Then, we will assess how genetic ablation of tuft cells or PGD2 impacts polyp formation. The goal of this pilot is to determine whether the tuft cell-PGD2 axis is active and functionally relevant in FAP, potentially paving way for safer, more targeted, and personalized chemoprevention strategies for patients with this condition.
