Case Western Reserve University School of Medicine, Cleveland, has received a $2.1 million grant from the National Center for Research Resources, part of the Nationaal Institutes of Health , to expand basic research models for the study of cystic fibrosis (CF). The 4-year NIH grant was awarded to Mitchell Drumm, PhD, and Craig Hodges, PhD, co-investigators of the research supported by the grant.
Drumm is professor of pediatrics and genetics at Case, and vice chair for research in pediatrics. Hodges is an assistant professor of pediatrics and genetics, also at Case.
Drumm and Hodges have collaborated to develop and study a series of basic research models that have contributed significantly to the research community’s understanding of CF and examined the effects of correcting the genetic defect in CF using these models. The newly secured grant provides the researchers with the resources necessary to advance CF research through the development of additional basic research models.
“Basic research is critical in helping investigators pinpoint the cellular and molecular mechanisms that cause CF in order to determine how they can be reversed,” Drumm said. “As there are currently a number of therapeutic approaches designed to correct CF gene function, it is important to understand what aspects of the disease can be corrected, or even reversed.”
Such research entails the study of mouse genetics to better understand CF. Drumm and Hodges co-direct an animal core facility with the most comprehensive collection of CF mouse models in the world. With the new NIH grant, Drumm and Hodges plan to generate even more of these basic research models.
The models developed thus far include mice with different versions of the CF gene, each with a different amount of function, so that researchers can determine the critical levels of the gene function for the manifestation of any disease-related characteristic.
Recently, these researchers generated models that allow them to turn the CF gene on or off in different organs of the body, or at different times in the life of the animal. Turning the gene off enables researchers to determine how the gene directly and indirectly affects different organs, while turning it on allows researchers to assess the effects of correcting the CF gene. Their work with these mice has shown that the effects of the disease on the lungs and digestive system are more complex than originally thought, involving not only the cells lining those organs, but also the immune system and other types of cells. One of the apparent ramifications is that there may be targets for therapy not previously considered.
“Our hope is that we’ll find out where in the body and when we need to focus our attention for therapies,” say the researchers. “This is a devastating disease for the children affected by it, and for their families, so anything we might do to improve the health of these kids would be of great significance.”
Source: Case Western Reserve University
