OHSU Student Receives National Honors for Liver Disease Discovery

11/02/99    Portland, Ore.

26-year-old Kara Manning was trying to unravel the secrets of a sometimes deadly liver disease. But instead of one discovery, the Oregon Health Sciences University predoctoral student made two. Now, she's receiving national honors for work that could someday result in the development of a new life-saving drug.

Recently, Manning was honored with a student award following her presentation at a national meeting of the American Society of Human Genetics. Manning's work centers on a genetic liver disease called tyrosinemia, which sometimes surfaces in a newborn's first month of life. An acute form of the disease may cause babies to have trouble gaining weight. Other symptoms include an enlarged liver and spleen, malfunctioning kidneys, and nose bleeds. For many patients, this form of tyrosinemia is deadly. Those who do survive may be at high risk for tumors or cirrhosis of the liver.

Tyrosinemia is caused by a defect in one of the metabolic enzyme pathways of the body due to a genetic mutation. It leads to a buildup of a toxic chemical in the liver. This chemical buildup normally would not occur in a person without the defect.

Manning's project was to use a mouse model to investigate new therapies for tyrosinemia. Through mouse breeding, she studied the combinations of mutated and normal genes that would result in the disease. Specifically, she and other researchers were hoping to breed a mouse with a less serious liver disease called alkaptonuria from parent mice with tyrosinemia. In the end, the experiment was a success. However, their work also resulted in a second surprising revelation.

Manning and her colleagues discovered a genetic combination that resulted in a form of alkaptonuria, which underwent a suppressor mutation. This means the illness was able to heal itself over time. Until now, scientists knew of the self-healing form of the disease, but they knew little about its cause. The experiment also allowed them to study the self-healing properties of the disease in a laboratory setting, something that had never been done before in a mammal.

Manning's success in breeding mice with alkaptonuria from parent mice with tyrosinemia may provide hope for couples who want to have children but are concerned about a history of the disease in their family. It is hoped that some time down the road, a drug may be developed to transform tyrosinemia in newborns into the milder alkaptonuria. While the child would not be disease-free, the life-threatening disease would be transformed. However, Manning and her colleagues say development and testing of such a drug may be years away.

Manning says the award recognizes the hard work of basic science students in labs across the campus of OHSU. She also hopes her work will help the university as a whole. "The entire genetics department should be proud," said Manning. "OHSU is already well-respected worldwide for its accomplishments and teaching, and this award is just one of many honors that gives us more international recognition."

Manning's faculty advisor Markus Grompe, M.D., professor of molecular and medical genetics, and pediatrics in the School of Medicine at OHSU, says the award is a tremendous honor for both Manning and the university. "This award is given to only one student each year, and the work is selected from hundreds of competing abstracts from all around the world," Grompe said. "It is, therefore, an accomplishment that Kara can be very proud of. It also illustrates the high caliber of the Ph.D. graduate students at OHSU. Working with bright young people like her is a big part of the fun in science."

Manning's work appears in the Oct. 12 issue of the Proceedings of the National Academy of Sciences.

Editor's Note: Kara Manning and Markus Grompe, M.D., are available for interviews. Contact Jim Newman in University News and Publications at (503) 494-8231 for more information.