Dr. Richard E. Honkanen, professor of biochemistry at the USA College of Medicine, was recently awarded a five-year Transformative Research Project Award by the National Institutes of Health. The grant award totals $ 1,695,625. Dr. Honkanen was only one of 17 researchers across the United States to receive the highly competitive award this year.
According to Dr.Honkanen, the grant will help fund a research project that could change the way we treat high cholesterol in the future.
Dr. Honkanen said that for most people, having a heart attack or stroke is a lifestyle choice. “Most people that have a heart attack or stroke choose to eat a poor diet, do not get enough exercise, or do not take the advice of their physician,” he said. “However, children suffering from a rare form of high serum cholesterol, called familial hypercholesterolemia, have heart attacks before they reach their teenage years and do not respond to available treatment options. To develop a treatment for children with familial hypercholesterolemia, we needed to think outside of the box.”
For both children with familial hypercholesterolemia and most people with cardiovascular disease, the process leading to a heart attack or stroke starts with the development of atherosclerosis, a common disorder that occurs when fat, cholesterol, and other substances build up in artery walls and form abnormal structures called plaques.
“If our bodies could break down excess cholesterol in the developing plaques, we would not likely develop the serious health threats that occur over time such as heart attacks and strokes,” Dr. Honkanen said.
“In this research project, we will develop methods to safely engineer human immune cells, adapting a strategy used by bacteria to allow macrophages, or natural defense cells, to metabolize cholesterol,” he added. “In humans, the inability of macrophages to break down cholesterol represents a critical early event in the maladaptive immune response that leads to the onset and progression of atherosclerosis.”
Dr. Honkanen said that in order to develop an entirely new therapy, they plan to introduce humanized versions of genes from bacteria that can feed on cholesterol into human immune cells. “If successful, the transformed cells would gain the ability to ‘eat’ the cholesterol in the plaques of the arteries of people with disease, providing a new approach for the prevention of heart attacks and strokes.”
According to Dr. Honkanen, the key to the research project is to develop a therapy that will be safe. “We must make sure the new therapy does not cause negative consequences by removing too much cholesterol, which is an essential component of all human cells” he said. “We need to only get rid of the excess cholesterol, which will require the development of new regulatory controls.”
The Common Fund’s NIH Director’s Transformative Research Projects Program was specifically created to support exceptionally innovative, high risk, original and/or unconventional research projects that have the potential to create or overturn fundamental paradigms. These projects tend to be inherently risky, but if successful can profoundly impact a broad area of biomedical research.
The primary emphasis of the Transformative Research Projects Program is on creative ideas and projects that have the potential to transform a field of science and to provide adequate support for the work.
For more information on the program, visit
http://commonfund.nih.gov/T-R01.
