The Busada Lab
Department of Microbiology, Immunology, and Cell Biology
West Virginia University School of Medicine
Gastric cancer is the 5th most common cancer in the world. Most cases of gastric cancer are associated with infection by the bacteria Helicobacter pylori. The infection causes massive gastric inflammation, which damages the stomach, and promotes gastric carcinogenesis. The factors that regulate gastric inflammation and how the inflammatory microenvironment promotes cancer development are unclear. Our goal is to understand how inflammation promotes gastric cancer development to facilitate the discovery of new gastric cancer diagnostics and treatments.
Research Projects
Glucocorticoid Regulation of Gastric Inflammation and Carcinogenesis
Glucocorticoids are steroid hormones produced by the adrenal glands. These hormones function as the brake pedal for the immune system. Within the stomach, glucocorticoids are critical for regulating the intensity of gastric inflammation. We've recently shown that disruption of glucocorticoid signaling quickly leads to spontaneous stomach inflammation. Type 2 innate lymphoid cells (ILC2s) and macrophages are at the forefront of this pathogenic inflammatory response, damaging the stomach and leading to the development of potentially precancerous spasmolytic polypeptide-expressing metaplasia (SPEM). We are currently investigating the role of glucocorticoid signaling in controlling inflammation during Helicobacter pylori infection. We hypothesize that disruption of glucocorticoid signaling during Helicobacter pylori infection leads to a more severe inflammatory response and promotes gastric cancer development.
Sex Hormone Regulation of Gastric Inflammation
Inflammation is regulated differently in males and females. Females typically have a more robust inflammatory response than men. While this provides greater protection from infection, women are more susceptible to autoimmune and chronic inflammatory diseases. Sex can influence inflammation through a host of different mechanisms ranging from lifestyle to sex chromosomes. We have found that androgen's, the male sex hormone, suppress gastric inflammation by regulating ILC2 activation. Interestingly, sex also affects gastric cancer, and cancer rates in men are nearly double rates in women. This relationship between men being protected from inflammation yet being more susceptible to gastric cancer is somewhat confusing. Androgen's may promote an alternative immune response that protects from inflammatory damage at the expense of immune surveillance for cancer. Our lab is currently investigating the important relationship between sex, inflammation, and gastric cancer.
Busada et al. 2021. Gastroenterology
Impact of cigarette smoke on H. pylori pathogenesis
Cigarette smoking is a well-established, independent risk factor for gastric cancer. Among H. pylori-infected individuals, smoking dramatically amplifies gastric cancer risk, with smokers facing up to an 11-fold increased risk compared to non-smokers or H. pylori-negative smokers. Despite this, the mechanisms by which cigarette smoke (CS) interacts with H. pylori to promote carcinogenesis remain poorly understood. Our work has shown that CS exposure suppresses the gastric inflammatory response to H. pylori, blunting gastric atrophy and metaplasia development. Since these pathological features are used in the clinic to diagnose H. pylori infection, our findings suggest that smoking suppresses H. pylori clinical detection. Thus, smokers may have an increased incidence of undiagnosed H. pylori infection.
