Skip to Main Content

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

Complete NCBI Publications

Studies in my laboratory focus on spatiotemporal regulation of protein-protein interactions governing GPCR signaling and function. We are especially interested in the parathyroid hormone receptor (PTHR), which controls extracellular mineral ion homeostasis and bone turnover. Key advances have been made in understanding cell-specific PTHR signaling, trafficking, and post-translational modifications.

Recent observations indicate that PTHR activation, desensitization and endocytosis are mediated through distinct structural states that derive from specific interactions between ligand andreceptor. Agonist- or antagonist-occupied receptor states induce discrete conformations with accessibility to intracellular receptor domains. The differential or inducible involvement of these domains in coupling to G proteins may represent a molecular basis for ligand-selective responses notonly for the PTHR, but also for other G protein-coupled receptors, and are novel drug targets.

Current work is directed at elucidating the molecular and structural mechanisms of how cytoplasmic PDZ proteins such as NHERF1 legislate cell-, ligand-, and stage-specific receptor trafficking. 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.

Tatyana Mamonova, PhD

Dr. Mamonova's research focuses on molecular modeling of the interactions of the adapter protein EBP50/ NHERF1 with its target ligands, including parathyroid hormone receptor and type II sodium-dependent phosphate co-transporters. The goal of these studies will contribute to our understanding and prediction of conformational reorganization and the structure-function relationships in NHERF1 proteins associated with the ligand binding. The results will provide insights into developing drugs for selective therapeutic applications.

Headshot of Peter A. Friedman, PhD
Peter A. Friedman, PhD

Headshot of Tatyana Mamonova, PhD
Tatyana Mamonova, PhD
Research Assistant Professor

Peter A. Friedman, PhD

Journal Articles

Suva LJ and Friedman PA. Structural Pharmacology of PTH and PTHrP. Vitam Horm 120, 2022.
Nolin TD and Friedman PA. Agents Affecting Mineral Ion Homeostasis and Bone Turnover. In: Goodman & Gilman's The Pharmacological Basis of Therapeutics (14 ed.), edited by Brunton LL, Knollman B and Hilal-Dandan R. New York: McGraw Hill, 2022.
Vistrup-Parry M, Sneddon WB, Bach S, Stromgaard K, Friedman PA and Mamonova T. Multisite NHERF1 phosphorylation controls GRK6A regulation of hormone-sensitive phosphate transport. J Biol Chem 296: 100473, 2021.
Zhang Q, Gefter J, Sneddon WB, Mamonova T and Friedman PA. ACE2 interaction with cytoplasmic PDZ protein enhances SARS-CoV-2 invasion. iScience 24: 102770, 2021.
Mamonova T and Friedman PA. Noncanonical sequences involving NHERF1 interaction with NPT2A govern hormone-regulated phosphate transport: binding outside the box. Int J Med Sci 22: 1087, 2021.
Zhang Q and Friedman PA. Receptor-Loaded Virion Endangers GPCR Signaling: Mechanistic Exploration of SARS-CoV-2 Infections and Pharmacological Implications. Int J Mol Sci 22: 10963, 2021.
Ardura JA, Alvarez-Carrion L, Gutiérrez-Rojas I, Friedman PA, Gortazar AR, and Alonso V. Mindin secretion by prostate tumors induces premetastatic changes in bone via β-catenin. Endocr Relat Cancer 27: 441-456, 2020.
Suva LJ and Friedman PA. PTH and PTHrP Actions on Bone. Handb Exp Pharmacol 262: 27-46, 2020.

Tatyana Mamonova, PhD

Journal Articles

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.