Dr. O’Keefe performs translational research into the physiological and pathophysiological responses to feeding and nutritional deprivation. He has recieved NIH R01 grant support for his studies on the physiological effects of feeding on pancreatic enzyme synthesis in humans with and w/o disease, the optimal feeding in patients with severe acute pancreatitis, and most recently the role of diet, the microbiome and its metabolites in determining colon cancer risk in extreme risk Alaska Native People, high risk African Americans (AA), and minimal risk rural South Africans (NA).

His pivotal study in Nature Communications 2015 showed that switching the diets of AA and NA (i.e. Americans were given a traditional African diet high in fiber, low in meat and fat, whilst Africans were given a westernized diet high in meat and fat, low in fiber) led to profound changes in the colonic microbiome and its metabolome, associated with reciprocal changes in colonic mucosal biomarkers of cancer risk within 2 weeks. This supports the hypothesis that diet drives colon cancer risk and that it is largely preventable by a high fiber diet. Studies are underway in Alaska to determine whether fiber supplementation will annul the health disparity and extreme rates of colon cancer risk and mortality in Alaska Natives.

Finally, Dr O'Keefe is partnering with the University of Stellenbosch in South Africa to develop the African Microbiome Institute, which plans to study the ecology of the microbiome through the Faculties of Medicine, Agrisciences, and Plant Biology, with the overarching aim of improving life.atocellular carcinoma.

Dr O'Keefe's research interests are linked to his clinical interests. He has 40 years experience in nutritional gastroenterology, stimulated by his unique combination of postgraduate degrees in Medicine and Human Nutrition. His theses were based on the application of stable isotope labeling techniques of amino acids to measure in vivo protein metabolic responses in humans to a variety of GI diseases, including surgical trauma, liver failure, acute and chronic pancreatitis, the short bowel syndrome and intestinal transplantation. These measurements were used to determine the acute metabolic effects of these diseases and their associated rates of protein catabolism to design the most effective forms of metabolic support of malnourished hospitalized patients.

Their application of these techniques led to paradigm changes in the routine enteral and parenteral nutritional support, summarized in his solo authored "The Principles and Practice of Nutritional Support" (Springer Publ 2015). Dr O'Keefe has played a leadership role in the nutritional support of hospitalized patients, patients with intestinal failure dependent on home IV and enteral feeding, and patients following small bowel transplantation at UPMC. His research into the etiology of colon cancer has added the clinical interest of improving peoples' diets to prevent colon cancer, the second leading cause of cancer deaths worldwide.