Friedman Lab

 

Studies in Dr. Friedman's laboratory focus primarily on the mechanism and regulation of calcium transport across cell membranes. Experimental work is presently directed toward characterizing the interactions between the calcium-sensing receptor (CaSR) and parathyroid hormone (PTH) on calcium absorption by renal thick ascending limbs and distal tubule cells.

Problems under investigation include: 1) delineating the role of the CaSR in controlling basal and PTH-dependent calcium absorption; 2) determining the role of calcium channel subunits in regulating distal tubule calcium absorption; and, 3) defining structural elements in the PTH receptor responsible for signaling and internalization.

Techniques applied to these studies include cell culture models, isolated perfused single tubules, and clearance studies in transgenic mice. Single cell fluorescence, tracer flux measurements, heterologous receptor expression, antisense depletion techniques, biochemical and molecular analyses of second messenger formation are routinely applied. Elucidation of the mechanism of PTH receptor signaling will not only explain the physiological action of PTH at one of its principal target sites but also provide insight into novel mechanisms by which cell specific signaling is conferred. The resulting information will be valuable in understanding mineral ion homeostasis under normal conditions, as well as disordered calcium balance in renal failure, hyperparathyroidism, or osteoporosis. The results will provide insights into analogs that may be candidates for selective therapeutic applications.


Peter A. Friedman, PhD
Professor


Tatyana Mamonova, PhD
Research Assistant Professor

Peter A. Friedman, PhD

Nolin TD and Friedman PA. Agents Affecting Mineral Ion Homeostasis and Bone Turnover. In: Goodman & Gilman's The Pharmacological Basis of Therapeutics (13 ed.), edited by Brunton LL, Knollman B and Hilal-Dandan R. New York: McGraw Hill, 2018, p. 887-906.
 
Vilardaga JP and Friedman PA. Molecular Biology of Parathyroid Hormone and Calcium Signaling. In: Textbook of Nephro-Endocrinology: Hormones and the Kidney (2 ed.), edited by Singh AK and Williams GH. San Diego: Academic Press, 2018, p. 523-537.
 
Zhang Q, Xiao K, Liu H, Song L, McGarvey JC, Sneddon WB, Bisello A and Friedman PA. Site-specific polyubiquitination differentially regulates parathyroid hormone receptor-initiated MAPK signaling and cell proliferation. J Biol Chem 10.1074/jbc.RA118.001737, 2018.

 
Ardura JA, Alonso V, Esbrit P and Friedman PA. Oxidation inhibits PTH receptor signaling and trafficking. Biochem Biophys Res Commun 482:1019-1024, 2017.
Mamonova T, Zhang Q, Chandra M, Collins BM, Sarfo E, Bu Z, Xiao K, Bisello A and Friedman PA. Origins of PDZ binding specificity. a computational and experimental case study using NHERF1 and the parathyroid hormone receptor. Biochemistry 56:2584-2593, 2017.
Pavlos NJ and Friedman PA. GPCR Signaling and Trafficking: The long and short of it. Trends Endocrinol Metab 28: 213-226, 2017.
Suva LJ and Friedman PA. PTH regulation of FGF23 fragments: A Tail in Two Acts. Endocrinology 158: 1106-1108, 2017.
Kittikulsuth W, Friedman PA, Van Hoek A and Kohan DE. Identification of adenylyl cyclase isoforms mediating parathyroid hormone- and calcitonin-stimulated cyclic AMP accumulation in distal tubule cells. BMC Nephrol 18: 292, 2017.
 
Mamonova T, Zhang Q, Chandra M, Collins BM, Sarfo E, Bu Z, Xiao K, Bisello A, and Friedman PA. Origins of PDZ binding specificity. a computational and experimental case study using NHERF1 and the parathyroid hormone receptor. Biochemistry 56:2584–2593, 2017.
 
Pavlos NJ and Friedman PA. GPCR Signaling and Trafficking: The long and short of it. Trends Endocrinol Metab 28:213-226, 2017.
 
Suva LJ and Friedman PA. PTH regulation of FGF23 fragments: A Tail in Two Acts. Endocrinology 158:1106-1108, 2017.
 
Sneddon WB, GW Ruiz, LI Gallo, K Xiao, Q Zhang, Y Rbaibi, OA Weisz, GL Apodaca and PA Friedman. Convergent signaling pathways regulate parathyroid hormone and fibroblast growth factor-23 action on NPT2A-mediated phosphate transport. J Biol Chem 291:18632-18642, 2016.
 
McGarvey JC, K Xiao, SL Bowman, T Mamonova, Q Zhang, A Bisello, WB Sneddon, JA Ardura, F Jean-Alphonse, JP Vilardaga, MA Puthenveedu and PA Friedman. Actin-sorting nexin 27 (SNX27)-retromer complex mediates rapid parathyroid hormone receptor recycling. J Biol Chem 291:10986–11002, 2016.
 

Mamonova T, Zhang Q, Khajeh JA, Bu Z, Bisello A and Friedman PA. Canonical and noncanonical sites determine NPT2A binding selectivity to NHERF1 PDZ1.  PLoS ONE 10:e0129554, 2015.


Tatyana Mamonova, PhD

Mamonova T, M Kurnikova and PA Friedman.  Structural basis for NHERF1 PDZ domain binding.  Biochemistry 51:3110-3120, 2012.
Mamonova T, AV Glyakina, MG Kurnikova and OV Galzitskaya.  Flexibility and mobility in mesophilic and thermophilic homologus proteins from molecular dynamics and fold unfold method.  J Bioinfo Comput Biology 8:1-18, 2010.
Mamonova T, K Speranskiy and M Kurnikova.  Interplay between structural rigidity and electrostatic interactions in the ligand binding domain of GluR2.  Proteins: Structure, Function and Bioinformatics 73:656-671, 2008.
Mamonova T, K Speranskiy and M Kurnikova.  Interplay between structural rigidity and electrostatic interations in the ligand binding domain of GluR2.  Proteins:  Structure, Function and Bioinformatics 73:656-671, 2008.
Mamonova T and M Kurnikova.  Structure and energetic of channel forming protein-polysaccaride complexes.  J Phys Chem 110:25091-25100, 2006.