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Home > Directory > Primary Faculty > Peter A. Friedman, PhD

Peter A. Friedman, PhD

Professor
E1356 Biomedical Science Tower
200 Lothrop Street
Pittsburgh, PA 15261
paf10@pitt.edu
Phone: 412-383-7783
Fax: 412-648-1945

Education

BA (Zoology), Syracuse University, 1970
PhD (Pharmacology), SUNY Upstate Medical Center, 1975
Postdoctoral Fellow (Pharmacology), University of Lausanne, Switzerland, 1975-1977
Postdoctoral Fellow (Physiology), Cornell University Medical College, 1977-1979
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.

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.

Sponsored Research

RGS14 Regulation of Hormone-sensitive NPT2A Phosphate Transport
  - 8/1/2021 - 6/30/2026
NIH - R01GM140632-A1
Functional Polarity of PTH Receptor Signaling: Cellular and Molecular Mechanisms - 8/20/2017 - 6/30/2021
NIH - R01DK111427
Hormonal Regulation of NHERF1 in Bone - 12/28/2015 - 11/30/2019
NIH - R01DK105811