From left, Drs. Agnes Fogo, Matthew Breyer and Raymond Harris are leading the pilot studies to spark new research in Nephrology. (photo by Dana Johnson)
Nephrology renews grants, legacy of kidney research
The Divisions of Adult and Pediatric Nephrology have preserved their legacy as leaders in research with successful renewals of awards from the National Institute for Diabetes and Digestive and Kidney Diseases for the Vanderbilt George O’Brien Kidney Research Centers. The grants filters a total of $10 million into the Medical Center over five years for research projects in their respective fields.
Vanderbilt is the only institution with both adult and pediatric awards, and it’s the only program that has been continually funded for both avenues of research since the awards’ inception; the adult project began in 1987 with Dr. Harry R. Jacobson, then the chief of Nephrology and now vice chancellor for Health Affairs, as the principal investigator, and the pediatric project started in 1992 with Dr. Iekuni Ichikawa, then professor of Pediatrics and Medicine, as the PI.
Today, Dr. Agnes Fogo, professor of Pathology, Medicine and Pediatrics, directs the pediatric O’Brien Center research. Dr. Raymond Harris, the Ann and Roscoe R. Robinson Professor of Medicine and chief of Nephrology, leads the adult studies. Dr. Matthew Breyer, Catherine McLaughlin Hakim Professor of Nephrology, continues to serve as the associate director of the adult center. The grants this year had a new requirement: pilot studies to spark new research.
The general goal of all the projects — four each in adult and pediatrics — is to better understand the progression of kidney damage by studying the biological and molecular mechanisms that contribute to progressive kidney disease.
“Once kidney damage begins, we frequently see the damage become progressive and get worse over the life of the individual, leading to the need for dialysis or transplantation,” said Breyer.
Much of the research will build on a foundation established by the Vanderbilt researchers, the role of COX-2 in progressive kidney damage.
In 1994, Breyer and Harris reported that COX-2 is expressed in the kidneys, a surprising finding at that time. COX-2 was known to play a role in blood pressure; their later studies indicated that COX-2 also plays a role in kidney damage. COX-1 also has a role, but it’s still undetermined, Breyer said.
Breyer and Harris each have projects that will further investigate COX-2. Harris will further investigate COX-2 in progressive renal injury; Breyer will look specifically at prostenoids derived from the enzyme and their function in renal growth and injury.
In other adult projects, Dr. Takamune Takahashi, research assistant professor of Medicine, will examine vascular injury and the role of angiogenesis in diabetic nephropathy and endothelial dysfunction, and Fogo will look at the role of angiotensin II in progressive renal injury and the mechanisms of age-related fibrosis.
Under the adult pilot projects, Ambra Pozzi, Ph.D., assistant professor of Medicine and Cancer Biology, will study the role of alpha-1, beta-1 integrins in diabetic nephropathy; Mark de Caestecker, Ph.D., assistant professor of Nephrology, will lead a study titled Cited proteins in renal development and diseases; and Roy Zent, Ph.D., assistant professor of Nephrology and Cancer Biology, will look for markers of ureteric bud development.
The pediatric projects are: the study of the development of atherosclerosis related to the renin angiotensin system, by Dr. Valentina Kon; Ichikawa, who now splits his time between Nashville and his homeland Japan, will study the role of angiotensin Type 1 A receptors on macrophages and how they influence scarring; Dr. Allison Eddy, professor of Pediatrics at the University of Washington, will collaborate with a study of macrophage scavenger receptors in kidney scarring; and Fogo will continue a project that focuses on tubular interstitial fibrosis and the roles played by angiotensin, TGF-beta and plasminogen activator inhibitor-1.
There are three pediatric pilot studies. Dr. Kathy Jabs, director of Pediatric Nephrology, will try to establish markers of the potential risk of cardiovascular disease in children with renal insufficiency by using ultrasound to measure the thickness of carotid arteries in children with the disorder and comparing the data to the same measurement in otherwise healthy kids. Poornima Upadhya, Ph.D., will examine the role of TGF 1-beta in kidney scarring. Dr. Taiji Matsusaka, research assistant professor of Medicine, will look at the podocyte, a primary target in many kidney diseases that keeps protein from leaking across the glomerulus.
Harris credits the stability and continuity of senior scientists involved in the grants for their continued renewal. “We have outstanding researchers in adult and pediatric nephrology. Our researchers are able to work together; we have a long history of collaboration,” he said.
The O’Brien Centers’ grants are named for former U.S. congressman George O’Brien who died of prostate cancer. His widow lobbied congress to fund research centers for kidney and genitourinary diseases.