Ignacio A. Portales Castillo, MD

Washington University in St. Louis (WU)

My research is inspired directly by patients and focuses in two main areas 1) PTH receptor function, 2) Genetic causes of Fanconi Syndrome. During my clinical nephrology fellowship we studied patients with rare diseases affecting endochondral bone formation and our group identified a role for impaired ßarrestin recruitment leading to overstimulation of the PTH receptor pathway in Eiken disease. I also met a family with a rare form of Fanconi syndrome caused by mutations in a mitochondrial enzyme encoded by the gene GATM. Most of these patients progress to end-stage kidney disease. Motivated by the possibility of finding a treatment, I performed several in vitro studies to show regulation of the mutant protein by creatine in human cells including kidney organoids. We have now not only in vitro models, but also a novel mouse GatmP341L, which we use to study creatine metabolism and its relation to Fanconi syndrome.