Macrophage Pathogen Interactions in Regional Cystic Fibrosis Lung Inflammation

ABSTRACT
The goal of this K24 is to provide support to allow Dr. Ashare to spend an additional 25% of her
time mentoring junior physician scientists in patient-oriented research on inflammatory lung
disease. This K24 will provide the opportunity for Dr. Ashare to expand her program in patient-
oriented translational research, integrate new physician scientists and PhD scientists into her
research program, and allow for additional protected time so she can mentor additional trainees.
In addition, with the help of her senior advisory committee, she will also use this time to improve
her own mentoring skills. This K24 describes two aims that involve patient-oriented translational
research using primary lung macrophages obtained from human subjects. Each Aim will serve
as an individual project for a new trainee. Aim1 exploits preliminary findings that macrophages
isolated from different regions of the lung are metabolically different and will specifically
investigate the impact of increased glycolytic metabolism in upper lobe macrophages on the
generation of inflammation. This aim will also determine the role of succinate accumulation in
the generation of the macrophage inflammatory response. Based upon our data demonstrating
that there are phenotypic and genotypic differences in Pseudomonas aeruginosa isolates from
different regions of the CF lung, Aim 2 will test the hypothesis that regional P. aeruginosa
isolates differentially stimulate lung macrophage immune responses and exhibit different
responses to extracellular succinate. These two independent but complementary aims will allow
new trainees to pursue translational patient-oriented research projects that will lead to a greater
understanding of host-pathogen interactions in the CF lung.

Grant Number: 5K24HL150453-05
NIH Institute/Center: NIH
Principal Investigator: ALIX ASHARE