A University of Nebraska Medical Center researcher, Duygu Dee Harrison-Findik, Ph.D., has received a five-year, $1.1 million research grant from the National Institutes of Health (NIH) to study the regulation of iron metabolism in alcoholic liver disease.
Iron is essential to the body, as it is an oxygen-carrying mineral that boosts a person’s immune system, cognitive development and energy metabolism. Without it, a person becomes tired, irritable and even depressed.
Patients with liver diseases, such as alcoholic liver disease and chronic hepatitis C infection, frequently exhibit iron overload, and these increased iron levels in the liver are associated with hepatic injury and a poor prognosis.
An assistant professor of internal medicine in the section of gastroenterology-hepatology, Dr. Harrison-Findik wants to better understand the underlying mechanisms of iron accumulation, which are largely unknown.
Changes in intestinal permeability were thought to be the underlying mechanism of enhanced iron absorption in alcoholic liver disease, she said. However, her team’s recent findings, published in the Journal of Biological Chemistry (2006) and Hepatology (2007), strongly suggest that iron overload in alcoholic liver disease is a regulated event. The central player, she said, is an iron regulatory hormone called hepcidin, which is synthesized in the liver.
Alcohol-induced oxidative stress suppresses hepcidin transcription in the liver, which then leads to increased iron absorption in the intestine and iron accumulation in the liver. Iron and alcohol act synergistically to cause liver injury.
"We were delighted to see that Japanese researchers recently confirmed our findings and demonstrated that the same events not only happen with alcoholic liver disease, but also with chronic hepatitis C infection," Dr. Harrison-Findik said of the Japanese research team’s work that was published in Gastroenterology 2008 (vol. 134). "These findings are exciting because they indicate that different liver diseases share common pathways to induce iron overload and liver injury.
"More importantly, it opens up a window of opportunity to tailor common diagnostic markers and treatment schemes for liver diseases. It also highlights the importance of oxidative stress in liver diseases. The treatment with antioxidants may need to be revisited."
Through the grant, Dr. Harrison-Findik’s team will try to better understand the molecular mechanisms of oxidative stress and the involvement of mitochondria (energy-producing structures within cells) in the regulation of iron metabolism in alcoholic liver disease.
"Hepcidin already has been recognized as a potential diagnostic marker and a therapeutic agent in various iron disorders including anemia of chronic disease, iron-deficiency anemia and chronic kidney diseases," she said. "Our work indicates that hepcidin also is an attractive candidate for the treatment of liver diseases, whereby iron overload induces liver injury."
A native of Istanbul, Turkey, Dr. Harrison-Findik studied veterinary medicine at Istanbul University in Turkey (1983) and earned her Ph.D. at Justus-Liebig University in Giessen, Germany (1989). She did her post-doctorate training at Tufts University in Boston and the University of Adelaide Australia. She joined UNMC in 2002 when she followed her mentor, John Gollan, M.D., Ph.D., when he was named chairman of UNMC’s internal medicine department. Dr. Gollan has since moved up to dean of the UNMC College of Medicine, a position he has held for the past five years.
"Dee relishes a challenge and, in these economic times, for her to be funded on the first review is unusual and reflects the high quality of her work," Dr. Gollan said.
UNMC is the only public health science center in the state. Its educational programs are responsible for training more health professionals practicing in Nebraska than any other institution. Through their commitment to education, research, patient care and outreach, UNMC and its hospital partner, The Nebraska Medical Center, have established themselves as one of the country’s leading centers in cancer, transplantation biology, bioterrorism preparedness, neurodegenerative diseases, cardiovascular diseases, genetics, biomedical technology and ophthalmology. UNMC’s research funding from external sources now exceeds $82 million annually and has resulted in the creation of more than 2,400 highly skilled jobs in the state. UNMC’s physician practice group, UNMC Physicians, includes 513 physicians in 50 specialties and subspecialties who practice primarily in The Nebraska Medical Center. For more information, go to UNMC’s Web site at www.unmc.edu.