Liver disease and recovery research at UF garners $1.3 million grant
University of Florida researchers have received nearly $1.3 million from the National Institute of Diabetes and Digestive and Kidney Diseases to uncover ways to lessen liver damage by studying the body’s natural process for breaking down and removing injured cells.
During surgery or transplantation, surgeons stop blood flow to the liver, temporarily cutting off oxygen and nutrients. When blood rushes back to the organ afterward it often causes serious damage called ischemia/reperfusion injury.
Finding a way to boost cells’ natural cleanup process, -- and with it, older livers’ ability to recover from such stress-related injury -- would help patients recover after liver surgery. It could also increase the number of livers available for people on the transplant waiting list by reducing damage to the organs of potential donors, and may lead to therapies for other diseases such as cancer and neurological disorders.
“All diseases, including liver disorders, are the consequence of multiple, complicated changes in the body,” said principal investigator Jae-Sung Kim, an assistant professor of surgery in the UF College of Medicine. “I think the way to cure diseases is to fully understand complicated mechanisms. We can take advantage of our natural defense mechanism that was evolutionally developed to fight against many causes of illness.”
More than 16,000 people in the United States await liver transplants, according to the U.S. Department of Health and Human Services’ Organ Procurement and Transplantation Network. Only 7 percent of all liver donations since 1988 have come from people older than 65, despite the fact that they die at higher rates than people in other age groups.
The multidisciplinary UF research team, which includes principal investigator Christiaan Leeuwenburh Ph.D, chief of the biology of aging division in the department of aging and geriatric research, seeks to confirm earlier findings that the liver’s ability to recover from ischemia/reperfusion injury is linked to the process by which cells remove structures called mitochondria when they are damaged. Mitochondria provide the cell with energy.
They also found that the older livers are, the slower they are at responding to stress-related damage, partly because of lowered levels of a protein responsible for directing the cell clean-up process. Injured cells resumed normal activity when inundated with the protein, called Atg4B.
The researchers will study older mice to examine age-related changes in the cell clean-up process. They also will explore ways to boost that process and examine the resulting effect on damaged livers.
“There are many studies that have investigated liver injury in younger animals and mechanisms there, but these studies are unique because they’re studying older animals,” said Leeuwenburgh a member of the UF Institute on Aging. “Most liver injuries occur and liver resection interventions are done in older individuals.”
Knowing more about how the cell clean-up process works could pave the way for new therapies, not just for liver disease, but also for a variety of other illnesses.
“Growing evidence indicates that dysfunctional or impaired autophagy, cells’ natural clean-up process, is directly associated with various diseases, including autoimmune diseases, cancer, neurological disorders and diabetes,” Kim said. “Through this study, we would like to better understand basic molecular mechanisms of autophagy.”