| |
Research Description:
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.
Education:
B.A. (Zoology), Syracuse University, 1970.
Ph.D. (Pharmacology), SUNY Upstate Medical Center, 1975.
Postdoctoral Fellow (Pharmacology), University of Lausanne, Switzerland, 1975-1977.
Postdoctoral Fellow (Physiology), Cornell University Medical College, 1977-1979.
Important Publications:
- Alonso V, JA Ardura, B Wang, WB Sneddon and PA Friedman. A naturally occurring isoform inhibits parathyroid hormone receptor trafficking and signaling. J Bone Miner Res, in press, 2010
- Romero G, WB Sneddon, Y Yang, D Wheeler, HC Blair and PA Friedman. Parathyroid hormone receptor directly interacts with dishevelled to regulate beta-catenin signaling and osteoclastogenesis. J Biol Chem 285:14756-14763, 2010
- Friedman PA. Molecular biology of parathyroid hormone. In: Textbook of Nephro-Endocrinology: Hormones and the Kidney, edited by Singh AK and Williams GH. San Diego: Elsevier, p. 95-104, 2009
- Bernardo JF, CE Magyar, WB Sneddon and PA Friedman. Impaired renal calcium absorption in mice lacking calcium channel ß3 subunits. Can J Physiol Pharmacol 87:522-530, 2009
- Gamba B and PA Friedman. Thick ascending limb: The Na+:K+:2Cl− cotransporter, NKCC2, and the calcium-sensing receptor, CaSR. Pflugers Arch 458:61-76, 2009
- Garrido JL, D Wheeler, LL Vega, PA Friedman and G Romero. Role of phospholipase D in parathyroid hormone receptor type 1 signaling and trafficking. Mol Endocrinol 23:2048-2059, 2009
- Wang B, Y Yang, AB Abou-Samra and PA Friedman. NHERF1 regulates parathyroid hormone receptor desensitization: Interference with ß-arrestin binding. Mol Pharmacol 75:1189-1197, 2009
|
