Research seeks to improve treatment for cystic diseases

Polycystic kidney disease is a fairly common genetic disorder. It affects about 500,000 people in the United States and nearly 1 in 400 people worldwide. It is part of a broader grouping of genetic disorders known as ciliopathies, which can often be fatal and have no known cure.

Andrew Resnick, associate professor of physics and a member of the Center for Gene Regulation in Health and Disease (GRHD) at �ϰ������ϲʹٷ�����, is leading a multi-institutional research effort designed to better understand how these diseases advance and impact human health. Dr. Resnick has been awarded a $445,000 R15 grant from the National Institutes of Health (NIH), to investigate how fluid flow sensing by cells may impact ciliopathy disease development and ultimately disease treatment.

“Ciliopathy diseases, including many cystic diseases, are characterized by the structure and function of cilia, slender protuberances that extend from the cell body and help regulate overall cellular development,” adds Resnick, who also serves as associate dean of the College of Science and Health Professions at �ϰ������ϲʹٷ�����. “Unfortunately, we still know very little about why the cilia malfunction in ciliopathy patients or, more generally, how these protuberances actually sense fluid flow.”

Resnick’s team will create a series of experiments in which they will grow kidney cells,  manipulate their primary cilia, and measure how the cells’ response to fluid flow changes. The goal will be to better assess how the cilia/flow relationship operates and then examine how changes either to the cilia or to the flow affects the overall function of the cell.

“If fluid flow slows too much, cells can initiate a tissue repair function; conversely, if too much flow occurs the cells can also initiate undesired biological processes,” Resnick adds. “Through this project we hope to develop a better model for how the flow sensing system actually works and how genetic mutations alter the process. With this information, we could then begin to develop targeted genetic therapies or create flow perfusion protocols to directly slow disease development.”

The current project builds on previous pilot studies conducted by Resnick, which received support from NIH, GRHD and �ϰ������ϲʹٷ�����’s Office of Research. Organizational partners on the current grant include: Case Western Reserve University, the Cleveland Clinic, New Jersey Institute of Technology and the University of Illinois at Chicago.

The Center for Gene Regulation in Health and Disease was launched with a grant from the Ohio Third Frontier Commission in 2008 and was designated as a state Center of Excellence by the Ohio Department of Higher Education in 2010. The Center serves as the home for 15 faculty members from the Departments of Biological, Geological and Environmental Sciences; Chemistry; and Physics as well as over 50 graduate students within the �ϰ������ϲʹٷ�����/Cleveland Clinic joint Ph.D. programs in Regulatory Biology and Clinical-Bioanalytical Chemistry.

###