This federal Project Grant award from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), under the Diabetes, Digestive, and Kidney Diseases Extramural Research program (CFDA 93.847), aims to elucidate how the heme metabolite unconjugated bilirubin, both at toxic and beneficial levels, regulates liver and kidney function in primary human cells and organoids. The $380,625 award to Vanderbilt University Medical Center will fund three specific research aims: 1) determining how toxic bilirubin levels activate basolateral bilirubin efflux pumps in primary human hepatocytes, 2) investigating how beneficial bilirubin levels are sensed by human kidney organoids and the role of the nuclear receptor LRH-1, and 3) elucidating the molecular mechanisms by which nuclear receptors mediate these liver and kidney responses. This comprehensive, multi-year study will leverage VUMC's expertise in primary human cell and organoid models to advance the understanding of both the detrimental and beneficial effects of bilirubin on organ function.
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