Friday, May 9, 2025
5/9/2025
IMAGINE: Intestinal Metaplasia And Gastritis INtErception Study - ABSTRACT Infection with the common bacteria, Helicobacter pylori, is associated with a range of changes to the gastric mucosa, resulting in conditions which can have significant effects on a patient’s morbidity and quality of life, in addition to increasing risk of gastric adenocarcinoma. This proposal focuses on pre-malignant disease in the stomach through clinically-relevant investigation of the synergy between H. pylori and host response in patients with H. pylori infection and in gastric intestinal metaplasia (GIM). In clinical practice, H. pylori is only considered as present or absent. However, H. pylori strain-specific factors such as cytotoxin associated gene A, CagA, interfere with the host adaptive immune system to allow H. pylori colonization in gastric mucosa. In addition, H. pylori strains may carry antibiotic resistance genes that contribute to treatment failure and persistence of the H. pylori infection, a known risk factor for gastric cancer development. In this proposal, the IMAGINE: Intestinal Metaplasia And Gastritis INtErception Study, we aim to address major knowledge gaps relating to molecular information about H. pylori heterogeneity and the relationship to gastric mucosal changes and outcomes. Specifically, we will focus on generating new knowledge that will result in more effective H. pylori eradiation and new approaches to cancer interception in premalignant gastric disease through identifying factors associated with disease progression in patients with GIM. Our preliminary data suggest that in patients infected with H. pylori, higher bacterial load and antibiotic resistance are associated with increased risk of persistence. The combination of exposure to the CagA virulence factor with life stress exposures including current life-stress as well as adverse childhood experiences may be associated with risk of progression. We hypothesize that the combination of infection with virulent H. pylori strains and stress exposures synergistically contribute to the development of premalignant disease in the stomach. A strength of our research program is the establishment of proven recruitment strategies that have allowed us to build racially diverse cohorts, collecting detailed survey information as well as biospecimens, to study premalignant disease in a high-risk population. Our goal is to build knowledge of premalignant gastric disease that will help us address the starkly disparate outcomes related to H. pylori-infection in the US, given both increased rates of gastric cancer incidence and survival in Black patients. Through this work, we are also generating a large bank of gastric organoids including GIM from a diverse patient population. Our work is particularly relevant as current clinical guidelines for GIM recognize the racial differences but offer no guidance on how to incorporate this or knowledge of other risk factors into clinical Indeed, surveillance of GIM among any patients is currently not recommended and strategies for risk-stratification are lacking. Deeper understanding of the role of H. pylori-specific factors and host response may allow for personalized, precision H. pylori treatment as well as better screening and surveillance strategies for GIM, and ultimately gastric cancer interception.
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