Project 1 (Radiation-Induced Lung Disease):
The focus of this program is to identify the genes involved in the radiation-induced lung diseases of pneumonitis (alveolitis) and fibrosis. We have mapped murine strain differences in propensity to develop lung disease in a C57BL/6J and C3H mouse model and are currently using genetic variation defined in the mouse Hap Map, along with gene expression data and siRNA investigations to identify the underlying causal genetic variations. We are also collaborating with the Division of Radiation Oncology to investigate whether these genetic variations, identified in mice, predict for the normal tissue side effect in the clinic.
Project 2 (Cystic Fibrosis):
The intestinal microbiome has been shown to influence many human diseases including obesity, asthma, inflammatory bowel disease and autoimmune disorders. In Cystic Fibrosis, a common autosomal recessive disorder caused by mutations in the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene, there is significant lung disease caused by repeated cycles of bacterial infiltration and inflammation. In addition to the lung disease, patients also experience intestinal disease including obstruction, inflammation and bacterial overgrowth. In initial studies of both patients with Cystic Fibrosis and mouse models of Cystic Fibrosis, the intestinal microbiome appears to be altered. Using both Cftr knockout mice (Cftrtm1UNC) and ΔF508 mutation mice (Cftrtm1EUR), we are focused on how the altered Cystic Fibrosis intestinal microbiome influences the immune environment and intestinal disease and to determine whether the intestinal microbiome of Cftr deficient mice influences the lung and intestinal disease which develops in this model.
These studies include characterization of the intestinal microbiome of cystic fibrosis mice using Illumina sequencing technology.