Deciphering the role of the cystic fibrosis transmembrane receptor (CFTR) in dietary fatty acid transport in the small intestine - program director/principal investigator (last, first, middle): kohan,…

The National Institute of Diabetes and Digestive and Kidney Diseases awarded the University of Pittsburgh $1.610 million on September 15, 2025, under the Diabetes, Digestive, and Kidney Diseases Extramural Research program (CFDA 93.847) to investigate the role of the cystic fibrosis transmembrane receptor (CFTR) in dietary fatty acid transport in the small intestine.

The research, led by Principal Investigator Alison B. Kohan and co-investigator C.A. Hodges, will test clinically relevant experimental diets and modulator therapy in gold-standard models of fat absorption and use patient-derived human intestinal organoids to quantify dietary fat absorption and chylomicron secretion. The work targets mechanisms of intestinal CFTR dysfunction and persistent nutritional defects in cystic fibrosis patients, with potential applicability to other malabsorptive and diarrheal diseases.

Performance takes place in Pittsburgh, Pennsylvania. The award runs through July 31, 2030.

Case Western Reserve University participates as a sub-recipient under a sub-award dated January 29, 2026, delivering collaborative work on the same research objectives.

Deciphering the role of the cystic fibrosis transmembrane receptor (CFTR) in dietary fatty acid transport in the small intestine - program director/principal investigator (last, first, middle): kohan, alison B (PI); hodges, CA (MPI) project summary though cystic fibrosis (CF) is considered a lung disease, IT presents in infancy as an intestinal disease leading to severe malnutrition and low body weight. These small intestinal symptoms are directly related to future respiratory failure and mortality rates. A major GAP in the field, even with modulator therapy, is determining the mechanisms of intestinal CFTR dysfunction and how to reverse the persistent nutritional defects in patients with CF. Using a novel surgical model and primary intestinal organoids, identified fatty acid (FA) trafficking across the apical epithelial membrane as the step of lipid absorption that is inhibited by CFTR-/-. Our studies will test clinically relevant experimental diets and modulator therapy in gold-standard models of FAT absorption and use patient- derived human intestinal organoids to directly quantify dietary FAT absorption and chylomicron secretion. The outcome of our studies could have a measurable impact on patients with CF, especially in early life, as these studies will fill a persistent GAP in knowledge about the activity of CFTR modulators in the intestine and mechanisms of FAT malabsorption (in CF and in other malabsorptive or diarrheal diseases).