Department of Pharmacology & Chemical Biology at the University of Pittsburgh
Peter A. Friedman, PhD
E1356 Biomedical Science Tower
200 Lothrop Street, Pittsburgh, PA 15261

Phone: 412-383-7783

Fax: 412-648-1945

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

Research Areas
Signal Transduction
Hormone Pharmacology
Hormone Signaling and Action
Pharmacology of Cell and Organ Systems
Receptor Pharmacology
Structural Pharmacology
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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.

Important Publications
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, 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.

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