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Gerda E Breitwieser, PhD

Senior Scientist


Weis Center for Research
100 North Academy Avenue
Danville, PA 17822
Phone: 570-271-6675
Fax: 570-271-6701


PhD, Washington University at St. Louis, 1982
Postdoctoral Training, University of Texas Medical Branch, Galveston, 1982-1987


G protein-Coupled Receptor Signaling, Protein-Protein Interaction, Signal Transduction, Cellular Regulation, Cardiovascular Sciences


Molecular biology and biochemistry, cell physiology, membrane protein trafficking, confocal and total internal reflection fluorescence microscopy


Laboratory of Molecular and Cellular Regulation of Calcium Sensing Receptors

The laboratory’s current focus is on calcium sensing receptors (CaSR). CaSR transduces local changes in extracellular calcium and metabolites (amino acids, polyamines) into intracellular signals, which include acute alterations in cell metabolism and secretion, and long term changes in cell proliferation and differentiation. CaSR is critical to organismal calcium homeostasis. Mutations, polymorphisms or altered expression of the CASR gene cause diseases of calcium homeostasis (familial hypocalciuric hypercalcemia (FHH) and neonatal severe hyperparathyroidism (NSHPT), autosomal dominant hypocalcemia (ADHH), primary & secondary hyperparathyroidism, hypercalcemia of malignancy), and contribute to the progression of cancers, diabetes, hypertension, bone and gastrointestinal disorders, and incidence of renal stones.

CaSR is among a subset of G protein-coupled receptors which are chronically exposed to agonist. Our laboratory has recently defined a novel mechanism, Agonist-Driven Insertional Signaling (ADIS), which accounts for the ability of CaSR to signal in the chronic presence of calcium. Key features of the mechanism  include a large, pre-plasma membrane pool of CaSR which can be mobilized to the plasma membrane upon exposure to increased extracellular calcium or other agonists, and constant, agonist-independent endocytosis of CaSR leading to the lysosome for degradation. The requirement for CaSR signaling to initiate trafficking has recently led us to re-interpret the defects of CaSR mutations which cause FHH/NSHPT, i.e., their trafficking to the plasma membrane is defective because of insufficient CaSR signaling. This insight explains the benign phenotype of FHH and argues for the use of calcimimetics in treatment of FHH/NSHPT.

Current research foci in the laboratory are:
• Adaptations of the CaSR ADIS mechanism in endothelial cells
• Signaling – biosynthesis coupling mechanism to maintain intracellular CaSR pools
• Linkage of CaSR mutations to disease (renal, cardiovascular)
• Endothelial cell regulation by calcium


Grant MP, Stepanchick A, Breitwieser GE. (2012, Dec). Calcium signaling regulates trafficking of familial hypocalciuric hypercalcemia (FHH) mutants of the calcium sensing receptor. Mol Endocrinol , 26(12) 2081-91.   

Cavanaugh A, Huang Y, Breitwieser GE. (2012, March). Behind the curtain: cellular mechanisms for allosteric modulation of calcium-sensing receptors. Br J Pharmacol , 165(6), 1670-7.   

Breitwieser GE. (2012, Sep). Minireview: the intimate link between calcium sensing receptor trafficking and signaling: implications for disorders of calcium homeostasis. Mol Endocrinol , 26(9), 1482-95.   

Huang Y, Cavanaugh A, Breitwieser GE. (2011). Regulation of stability and trafficking of calcium-sensing receptors by pharmacologic chaperones.. Adv Pharmacol , 62.143-73.   

Grant MP, Stepanchick A, Cavanaugh A, Breitwieser GE. (2011, Nov). Agonist-driven maturation and plasma membrane insertion of calcium-sensing receptors dynamically control signal amplitude. Sci Signal , 200, ra78.   

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