Institute researchers awarded major grant

Published 10:24 am Thursday, October 30, 2014

More than $1.6 million has been awarded to two lead scientists at The Hormel Institute, University of Minnesota for a collaborative research project on sepsis, a potentially life-threatening complication of infections that affects many people, including cancer patients.

The Hormel Institute’s Dr. Rhoderick Brown and Dr. Edward Hinchcliffe recently received funding approval for their portion of a nearly $4 million, five-year project with two other research institutions aimed at determining whether a new molecular target could lead to a potential cure for 65 percent of sepsis patients.

Sepsis, which annually strikes more than one million Americans, is the 10th-leading cause of death in the United States, with a mortality rate of more than 250,000 U.S. citizens per year.

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There have been numerous sepsis clinical trials but with limited success.

Sepsis is caused by an overwhelming immune response to infection that triggers inflammation and can lead to impaired blood flow damaging the body’s organs by depriving them of nutrients and oxygen. Often it results from an infection obtained while a person is hospitalized for treatment of another condition, such as cancer or heart disease. In severe cases, the patient can go into septic shock, which can lead to organs quickly failing and causing death.

“A critical need exists for new therapeutic approaches and treatments for sepsis, and our new molecular target provides hope for these patients who currently have no other effective therapies or alternatives,” said Hinchcliffe, leader of the Cellular Dynamics section at The Hormel Institute.

Anyone can get sepsis but those most at risk include people with weakened immune systems – such as cancer patients undergoing chemotherapy – children, infants and the elderly as well as those with chronic illnesses, including cancer, diabetes and AIDS, or those who have experienced a severe burn or physical trauma.

Funded by the National Heart, Lung and Blood Institute – part of the federal National Institutes of Health – the comprehensive project also will involve work by Dr. Charles Chalfant of Virginia Commonwealth University and Dr. Dinshaw Patel at Memorial Sloan-Kettering Cancer Center in New York. Drs. Brown and Hinchcliffe will bring biophysical and cell biology approaches to the project that will investigate the role of the cPLA2alpha/C1P interaction in regulating inflammatory processes that directly affect the blood/endothelial barrier.

U.S. Senators Amy Klobuchar and Al Franken along with U.S. Rep. Tim Walz assisted with the project’s grant application by writing letters of support.

During the summer of 2013 the same team of had related work published in the world’s leading scientific journal, “Nature.” That work was based on a discovery by Brown, leader of the Membrane Biochemistry section, and his team of a previously unknown protein (CPTP) in the body needed to prevent the overaccumulation of a sphingolipid known as ceramide-1-phosphate (C1P) within cells.

When the CPTP protein is depleted in cells, the inflammatory process becomes activated. Following the discovery, Brown’s team started collaborating with the other researchers, leading to the discovery of a new way to regulate the body’s pro-inflammatory eicosanoids, which contribute to the development of diseases, such as cancer, asthma or airway hyper-responsiveness, atherosclerosis and thrombosis.