Dr. Fred Wright, co-PI for new CF grant

Professor Fred Wright is a co-Principal Investigator for a new R01 award from the National Heart, Lung, and Blood Institute, entitled “Molecular Phenotypes for Cystic Fibrosis Lung Disease.” The $3.0 million, four- year grant will enable the collection of microarray gene expression data on 1200 participants in an ongoing study to map the genetic variants that determine the severity of lung disease in cystic fibrosis. Professor Michael Knowles of the UNC School of Medicine is the principal investigator of the mapping study, and is also co-Principal Investigator for the new grant. Wanda O’Neal, Assistant Professor of Medicine, will provide critical molecular biology expertise for growing the cell lines and obtaining genomic material to be used in the study.

The aim of the new grant is to elucidate the underlying biological mechanisms for the disease process, by examining which genes are turned on and off in individuals with cystic fibrosis, and relating these data to other clinical data in the patients. The data analysis will require the development of new computational and statistical methods, as the expression of 30,000 genes must be compared to additional data on about 600,000 genetic markers. The project is an example of a so- called “eQTL” (expression quantitative trait locus) study. Wright says that “a large number of genetic mapping studies are underway for a variety of diseases, but now we must move toward understanding the ‘why’ of such outcomes. To do this, we must gather more biological data and face the new analytic challenges. The new grant will be among the largest clinical eQTL studies of which I am aware.”

Drs. Fei Zou and Wei Sun are co-investigators on the project. Dr. Zou’s work on genetic association and controlling for possible confounds due to human population substructure will play a key role in the data analysis. Dr. Sun’s research on discovering transcriptional modules that control biological responses will also be extremely important, as the investigators seek to find parsimonious sets of genes and pathways that explain much of the variation in clinical severity of cystic fibrosis.