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Case Western Reserve Receives $2.1 M NIH Grant to Expand Cystic Fibrosis Research Models

Funding From National Center For Research Resources Will Fuel Gene Studies

July 26, 2011

CLEVELAND - Case Western Reserve University School of Medicine has received a $2.1 million grant from the National Center for Research Resources, part of the National Institutes of Health (NIH), to expand basic research models for the study of cystic fibrosis (CF).

CF is an inherited disease that causes thick, sticky mucus to build up in the lungs and digestive tract. The four-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 the Case Western Reserve School of Medicine, and vice chair for research in Pediatrics. He co-discovered the gene that causes CF, CFTR, along with Francis Collins, MD, PhD, the noted physician-geneticist and current director of the NIH. Hodges is an assistant professor of Pediatrics and Genetics at the Case Western Reserve School of Medicine as well.

Together, Drumm and Hodges have developed and studied 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 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. 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.”

Founded in 1843, Case Western Reserve University School of Medicine is the largest medical research institution in Ohio and is among the nation's top medical schools for research funding from the National Institutes of Health. The School of Medicine is recognized throughout the international medical community for outstanding achievements in teaching. The School's innovative and pioneering Western Reserve2 curriculum interweaves four themes--research and scholarship, clinical mastery, leadership, and civic professionalism--to prepare students for the practice of evidence-based medicine in the rapidly changing health care environment of the 21st century. Nine Nobel Laureates have been affiliated with the School of Medicine.

Annually, the School of Medicine trains more than 800 MD and MD/PhD students and ranks in the top 25 among U.S. research-oriented medical schools as designated by U.S. News & World Report's "Guide to Graduate Education."

The School of Medicine is affiliated with University Hospitals Cleveland Medical Center, MetroHealth Medical Center, the Louis Stokes Cleveland Department of Veterans Affairs Medical Center, and the Cleveland Clinic, with which it established the Cleveland Clinic Lerner College of Medicine of Case Western Reserve University in 2002.