Professor of Internal Medicine
- Infectious Diseases
Primary Office: D154 MTF
Iowa City, IA 52242
Web: Inflammation Program
BS, Biochemistry, University of California-Riverside
MS, Biochemistry, University of California-Riverside
PhD, Biochemistry, University of Wisconsin-Madison
Post Doctorate, Laboratory of Cellular Physiology and Immunology, and Laboratory of Signal Transduction, The Rockefeller University
Education/Training Program Affiliations
Interdisciplinary Graduate Program in Molecular and Cellular Biology
Interdisciplinary Graduate Program in Translational Biomedicine
Medical Scientist Training Program
"Research in my laboratory studies the mechanisms of pathogenesis of two Gram-negative bacteria –Francisella tularensis and Helicobacter pylori.
Helicobacter pylori, colonizes the gastric epithelium of half the world's population and plays a causative role in the development of peptic ulcers and gastric cancer. One hallmark of H. pylori is its persistence. H. pylori infection causes a massive influx of neutrophils (PMN) and mononuclear cells into the gastric mucosa, chronic gastritis, and damage to host tissue, but the immune response does not resolve the infection and the reasons for this host-defense defect are incompletely understood. Our long-term goal is to determine at the molecular level how H. pylori avoids being killed by the host innate immune system with a focus on bacteria-phagocyte interactions. At the present time our research in this area includes: 1) Identification of H. pylori virulence genes important for intracellular survival. 2) Characterization of the mechanism(s) by which H. pylori activates neutrophils and disrupts granule targeting. 3) Studying late stage of infection to eludicate the fate of infected neutrophils and their effects on the inflammatory response.
Francisella tularensis is a facultative intracellular pathogen and the causative agent of tularemia. Interest in this organism has increased recently because of its potential use as a bioweapon. It has long been known that Francisella replicates inside macrophages, and recent data indicate that several hours after upatake, these organisms breach the phagosome membrane and replicate in the macrophage cytosol. We have identified two receptors that mediate uptake of this bacterium by human macrophages and are beginning to define the composition of the compartment from which it escapes. Francisella also evades elimination by human neutrophils, and our data suggest a model in which early inhibition of the respiratory burst allows Franicsella to escape from neutrophil phagosomes and persist in the nutrient rich cytosol. To date we have identified six genes required for disruption of neutrophil function and defined two distinct mechanisms of NADPH oxidase inhibition. In addition, we have shown that F. tularensis modulates neutrophil gene expression to delay apoptosis and prolong cell lifespan and are collaborating with Brad Jones to identify novel virulence factors required for bacterial survival in macrophages. Current projects include: 1) Elucidation of the mechanisms of NADPH oxidase inhibition. 2) Defining how changes in neutrophil gene expression alter cell lifespan. 3) Identifying the mechanism of phagosome escape. 4) Role of host cell gene expression changes and microRNAs in modulating the inflammatory response during tularemia. 5) Role of PKC signaling in blockade of phagosome maturation in macrophages."
Date Last Modified: 06/06/2016 -