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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

PDZ proteins and mineral-ion homeostasis
 
Our lab focuses on the biochemistry underlying the regulatory mechanisms by which PDZ proteins such as NHERF1 and Scribble legislate PTH and FGF23 actions on signaling and the function of membrane receptors and transporters for phosphate and calcium. The overall goal of our work is to dissect the mechanism by which the NHERF1 PDZ protein platform integrates discrete but convergent signaling by the PTH receptor, a GPCR, and FGFR1, a structurally unrelated receptor tyrosine kinase to regulate NPT2A-mediated phosphate transport. A major thrust of the work is to characterize a cryptic internal PDZ ligand in NPT2A, which we advance as the hormone-sensitive control element associated with phosphate wasting in reported mutations. We are especially interested in characterizing the role of phosphorylation in dissembling the NPT2A-NHERF1-RGS14 complex, a vital step in hormone-regulated phosphate transport. We apply a combination of classical research tools, including cell-free and cell-based systems, molecular dynamics modeling, and state-of-the-art structural biological approaches.




 

Journal Articles

Sneddon WB, Friedman PA, and Mamonova T. Mutations in an unrecognized internal NPT2A PDZ motif disrupt phosphate transport and cause congenital hypophosphatemia. Biochem J 480: 685–699, 2023.
 
Stewart BZ, Mamonova T, Sneddon WB, Javorsky A, Yang Y, Wang B, Nolin TD, Humbert PO, Friedman PA and Kvansakul M. Scribble scrambles parathyroid hormone receptor interactions to regulate phosphate and vitamin D homeostasis. Proc Natl Acad Sci USA 120: e2220851120, 2023.
Friedman PA, Sneddon WB, Mamonova T, Montanez-Miranda C, Ramineni S, Harbin NH, Squires KE, Gefter JV, Magyar CE, Emlet DR, and Hepler JR. RGS14 regulates PTH- and FGF23-sensitive NPT2A-mediated renal phosphate uptake via binding to the NHERF1 scaffolding protein. J Biol Chem 298:101836, 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.

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