Jonathan Volmer, PhD, is a Postdoctoral Research associate under Dr. Richard Boucher.
Jonathan Volmer's work focuses on the development and use of tissue culture and animal models to examine the interactions of host environment, host response, and pathogen activity in cystic fibrosis lung disease. Hypoxic and inflammatory signaling pathways exhibit significant crossover and interaction. To examine the effects of this interaction, he maintains human tissue culture in controlled atmosphere conditions, with oxygen levels similar to those found clinically in the airway lumen, as opposed to traditional methods which maintain culture at atmospheric oxygen conditions. Although informative, only so much information can be obtained from isolated tissue cultures.
To address the impact on the whole organism, Volmer has developed a technique in which an infection with Pseudomonas aeruginosa, an organism commonly found in CF lungs, can be established and chronically maintained in the lungs of mice overexpressing the beta subunit of the epithelial sodium channel scnn1 (bENaC). bENaC and wild type (wt) mice were intratracheally challenged with a small volume (15uL) of low melting point agarose containing a low dose (1e4 cfu) of Pseudomonas aeruginosa. 21 days after the challenge, nearly 90% of wt mice had completely cleared the Pseudomonas challenge, and those wt mice still infected exhibited an average bacterial load of less than 50 cfu/mouse. However, more than 85% of the challenged bENaC mice maintained an active infection with Pseudomonas throughout the course of the challenge, with an average load of 6e3 cfu/mouse (fig1). The bacterial load did not significantly change through the course of the experiment.
The infection in bENaC mice led to a chronic mucopurulent obstructive inflammatory response in the airways characterized by neutrophil and lymphocyte infiltration (fig2), as well as mucus overproduction leading to obstruction of the airways and hypoxic regions of the airway lumen. These models will help dissect the pathways important in the development of the observed changes in the CF lung, and allow the investigation and comparison of clinical treatment regimens.
Please see Pubmed feed in righthand column for links to current publications.
Contact InformationPhone: (919) 966-9142