Center for Immunology and Infectious Diseases
SOM: Internal Medicine/Medical Microbiology & Immunology
University of California, Davis
Research Interest: Helicobacter pylori
Helicobacter pylori is a gram-negative spiral bacterium that was discovered in 1981 by Barry Marshall and Robin Warren, who in 2005 were awarded the Nobel Prize in Physiology or Medicine for their discovery. H. pylori infects the gastric mucosa of approximately half the world's population, and it is particularly common in developing countries. Although infection is asymptomatic in most cases, about 10% of those infected will develop peptic ulcer and 1-3% will develop gastric cancer, which is the second most common cause of cancer death in the world. The overall goal of the Solnick laboratory is to understand the pathogenic mechanisms by which H. pylori causes gastroduodenal diseases.
Functional Plasticity in the H. pylori Type IV Secretion System (T4SS)
Most strains of H. pylori that cause disease express a bacterial secretion system, a sort of molecular syringe that injects a bacterial protein inside the gastric cells and causes inflammation that can lead to peptic ulcer disease or gastric cancer. One of the essential components of the H. pylori secretion system is a protein called CagY, which is unusual because it contains a series of repetitive amino acid motifs that are encoded by a very large number of direct DNA repeats. We recently discovered that DNA recombination in cagY changes the protein motif structure and alters the function of the secretion system. Using mouse and non-human primate models, we have demonstrated that CagY is a sort of molecular rheostat that "tunes" the host inflammatory response, and likely contributes to persistent infection. The current focus of the lab is to address three questions regarding plasticity in the H. pylori T4SS. First, what is the mechanism by which recombination in CagY alters T4SS function? Second, how does the host immune response select cagY variants that alter T4SS function? Finally, what is the role of plasticity in the H. pylori T4SS during human infection? Determining the mechanism by which CagY functions will enhance our understanding of the effects of H. pylori on human health, and could lead to novel applications for the modulation of host cell function.