Clinicn Investigator, Full Prf Endocrine Division, Mass General Research Institute

Professor of Pediatrics Harvard Medical School

Pediatrician Pediatrics-Pediatric Nephrology, Massachusetts General Hospital

MD Medizinische Hochschule 1983

fgf23; fibroblast growth factor; gtp-binding protein alpha subunits gs; osteomalacia; parathyroid hormone; parathyroid hormone-related protein; pseudohypoparathyroidism; receptor parathyroid hormone; receptors parathyroid hormone; rickets; serum alkaline phostaphase activity; serum phosphorus levels; type 1; x-linked hypophosphatemia

Dr. Jueppner has been studying the regulation of calcium and phosphate homeostasis. After joining the Endocrine Unit in 1986, he worked initially on the characterization and then the molecular cloning of the PTH/PTHrP receptor (PTHR1) through an expression cloning approach.

Besides characterizing this G protein-coupled receptor extensively, additional investigations focused on defining inherited human disorders associated with an abnormal regulation of mineral ion homeostasis and bone metabolism.

In addition to determining the molecular cause of Jansen’s metaphyseal chondrodysplasia, infantile cortical hyperostosis, and different forms of hypo- and hyperphosphatemia, his efforts led to the discovery of microdeletions within or up-stream of the GNAS locus as the cause of autosomal dominant pseudohypoparathyroidism type Ib (PHP-Ib) and to the discovery of homozygous or compound heterozygous mutations in NPT2c (also referred to as NaPi-IIc) as the cause of hereditary hypophoshatemic rickets with hypercalciuria (HHRH).

He developed the first murine model of PHP-Ib and tested in vivo the effect of different PTH analogs on phosphate homeostasis and Npt2a/c expression.  For example, he showed that the acute phosphaturic actions of PTH are mediated through the cAMP/PKA pathway, while the long-term regulation of renal phosphate handling requires the IP3/PKC signaling pathway.

In addition, Dr. Jueppner developed one of the first assays for the measurement of FGF23, which was used for evaluating the role of this phosphaturic hormone in different disorders, particularly in patients with chronic kidney disease (CKD). He furthermore has expertise in the measurement of PTH through different immunoassays and using these measurements for predicting bone disease in CKD patients.