Ronald Rubenstein, MD, PhD

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Ronald Rubenstein, MD, PhD, is an Attending Pulmonologist in the Division of Pulmonary Medicine at Children's Hospital of Philadelphia.

Areas of Expertise: Advanced techniques for diagnosis and evaluation of cystic fibrosis, Noisy breathing in infancy, Novel pharmacotherapies for cystic fibrosis
Locations: Main Campus

Appointments and Referrals: 1-800-TRY-CHOP (1-800-879-2467)



Protein trafficking in cystic fibrosis. Dr. Rubenstein is pediatric pulmonologist interested in novel drug therapies for cystic fibrosis (CF). By understanding the molecular defects in the mutant CF conductance regulatory protein (CFTR), which is absent in the disease, Dr. Rubenstein and his colleagues aim to use novel pharmaceuticals to overcome these molecular defects and "repair" the dysfunctional CFTR. The researchers anticipate that such "protein repair" agents will improve the health of patients with CF.

Dr. Rubenstein and his colleagues have focused on the repair of the most common CFTR mutation, deltaF508-CFTR, which is not found at its appropriate location within epithelial cells. The researchers are studying one particular "protein repair" agent, sodium 4-phenylbutyrate (4PBA), which allows deltaF508-CFTR to reach the appropriate location in epithelial cells. They are using standard cell and molecular biology in vitro techniques in cultured cells and the Xenopus oocyte model expression system to assess the influence of 4PBA on proteins important in the intracellular trafficking of deltaF508-CFTR. As they identify 4PBA-regulated proteins that interact with deltaF508-CFTR, we aim to perform specific modulations of protein expression that will afford insight to the mechanism and repair of deltaF508-CFTR's aberrant intracellular trafficking. The researchers ultimately aim to extend and translate these observations into clinical trials of 4PBA and other "protein repair" agents.

Education and Training

Medical School

University of Texas Southwestern Medical School, Dallas, TS


Children's Hospital of Pittsburgh, Pittsburgh, PA

Board Certification

Pediatric Pulmonology

Titles and Academic Titles

Attending Pulmonologist

Director, Cystic Fibrosis Center

Richard B. Johnston, Jr. Endowed Chair in Pediatrics

Departments and Services



Yan W, Samaha FF, Ramkumar M, Kleyman TR, Rubenstein RC.  CFTR Differentially Regulates Human and Murine Epithelial Sodium Channels in Xenopus Oocytes. J Biol Chem. 2004 May 28; 279 (22):23183-92. Cited in PubMed; PMID: 15047694.

Samaha FF, Rubenstein RC, Yan W, Ramkumar M, Levy DI, Ahn YJ, et al.  Functional Polymorphism in the Carboxyl Terminus of the Alpha Subunit of the Epithelial Sodium Channel Alters Surface Expression in Xenopus Oocytes. J Biol Chem. 2004 Jun 4; 279 (23):23900-7. Cited in PubMed; PMID: 15069064.

Yan W, Suaud L, Kleyman TR, Rubenstein RC. Differential Modulation of a Polymorphism in the Carboxyl Terminus of the Alpha Subunit of the Human Epithelial Sodium Channel by Protein Kinase C d. Am. J. Physiol.-Renal Physiol. 2006 Feb; 290(2):F279-88. Cited in PubMed; PMID: 16174865.

Goldfarb SB, Kashlan OB, Watkins JN, Suaud L, Yan W, Kleyman TR,et al. Differential Effects of Hsc70 and Hsp70 on the Intracellular Trafficking and Functional Expression of Epithelial Sodium Channels. Proc. Nat. Acad. Sci. U.S.A., 2006 Apr 11; 103(15):5817-22. Cited in PubMed; PMID: 16585520.

Rubenstein RC. Abnormal Regulatory Interactions of I148T-CFTR and the Epithelial Na+ Channel in Xenopus Oocytes. Am. J. Physiol Cell Physiol, 2007 Jan;292(1):C603-11. Cited in PubMed; PMID: 16822950.

Antunes MB, Woodworth BA, Bhargave G, Xiong G, Aguilar JL, Ratner AJ, et al. Murine nasal septa for respiratory epithelial air-liquid interface cultures. Biotechniques. 2007 Aug;43(2):195-6, 198, 200 passim. Cited in PubMed; PMID: 17824387.

Kashlan OB, Mueller GM, Qamar MZ, Poland PA, Abner A, Rubenstein RC, et al. Small heat shock protein alphaA-crystallin regulates epithelial sodium channel expression.  J Biol Chem. 2007 Sep 21;282(38):28149-56. Epub 2007 Jul 30. Cited in PubMed; PMID: 17664274.

Suaud L, Yan W, Carattino MD, Robay A, Kleyman TR, Rubenstein RC. Regulatory interactions of N1303K-CFTR and ENaC in Xenopus oocytes: evidence that chloride transport is not necessary for inhibition of ENaC. Am J Physiol Cell Physiol. 2007 Apr;292(4):C1553-61. Epub 2006 Dec 20. Cited in PubMed; PMID: 17182731.

Yan W, Spruce L, Rosenblatt MM, Kleyman TR, Rubenstein RC. Intracellular trafficking of a polymorphism in the COOH terminus of the alpha-subunit of the human epithelial sodium channel is modulated by casein kinase 1. Am J Physiol Renal Physiol. 2007 Sep;293(3):F868-76. Epub 2007 Jun 27. Cited in PubMed;PMID: 17596527.

Rubenstein RC. Targeted therapy for cystic fibrosis: cystic fibrosis transmembrane conductance regulator mutation-specific pharmacologic strategies.  Mol Diagn Ther. 2006;10(5):293-301. Review. Cited in PubMed; PMID: 17022692.

Leadership and Memberships

CHOP Clinical Trials Research Affinity Group, Advisory committee member