Contents
- Cover Story
Forging a Path From Laboratory to Clinic
Critical Resources
Forging a Path From Laboratory to Clinic
Enabling Preclinical Studies and Their Translation to Patients
Daniel Marks and colleague Kevin Grove at the Oregon Health & Science University have been studying the effects of a high-fat diet on developing organs using a nonhuman primate animal model. These photographs show the livers of monkey fetuses whose mothers had been fed either a regular, low-fat diet (control) or a diet high in fat and calories. The livers were treated with a compound (oil-red O) that specifically stains fat deposits red. Many more fat deposits can be seen inside liver cells of fetuses in the high-fat diet group—a picture reminiscent of the fatty liver disease typically observed in alcoholics. (Images courtesy of Oregon Health & Science University)
Whereas many clinical insights come from basic studies in the laboratory, others have their roots in observations in animal models. Daniel Marks of Oregon Health & Science University received a pilot grant from the university’s CTSA to collaborate on a project initiated five years earlier by Kevin Grove at the NCRR-funded Oregon National Primate Research Center. “The pilot grant was so important, because I have not published in this field before,” says Marks, whose medical training was in pediatrics. “It is hard to apply for an R01 grant if you have no publication record.”
Grove had established a model of obesity in Japanese macaques by feeding them a diet consisting of 35 percent fat, the proportion of fat in the average U.S. diet. When given to pregnant monkeys, the diet invariably caused abnormalities in different organs in the developing fetuses. Marks documented an accumulation of fat in fetal liver cells associated with varying degrees of inflammation and scarring, a picture reminiscent of the liver disease typically observed in alcoholics. “To see this in the developing fetus is very alarming,” says Marks. “If the results are confirmed in humans, they would have profound implications in light of the current obesity epidemic.”
To examine this question, Marks started collaborating with physicians at the neonatal intensive care unit of the university’s affiliated hospital to examine the livers of human fetuses by ultrasound. “To set up a study like this, you must draft consent forms for the parents, in English and Spanish in this case, draft a procedure that details exactly what you want to do with the patient, the risks and benefits, how the data will be managed, how we will protect patient privacy, and so on,” Marks elaborates. He is receiving invaluable assistance from his institution’s CTSA in fulfilling these requirements.
