Ronald C. Rubenstein

faculty photo
Associate Professor of Pediatrics
Director, Cystic Fibrosis Center, The Children's Hospital of Philadelphia and the University of Pennsylvania
Member, Institute for Translational Medicine and Therapeutics, Perelman School of Medicine at the University of Pennsylvania
Scientific Director, Translational Core Lab, The Children's Hospital of Philadelphia
Richard B. Johnston, Jr. Endowed Chair in Pediatrics, The Children's Hospital of Philadelphia
Department: Pediatrics

Contact information
Pulmonary Medicine and Cystic Fibrosis Center
Abramson Center Room 410A
Philadelphia, PA 19104
Office: 215 590-1281
Fax: 215 590-1283
Graduate Group Affiliations
S.B. (Chemistry)
Massachusetts Institute of Technology, 1984.
Ph.D. (Pharmacology)
Medical Scientist Training Program, The University of Texas Southwestern Medical Center at Dallas, Southwestern Medical School, 1990.
Medical Scientist Training Program, The University of Texas Southwestern Medical Center at Dallas, Southwestern Medical School, 1991.
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Description of Research Expertise

Research Interests
Pharmacologic repair of mutant CFTR function in Cystic Fibrosis.

Key words: Cystic Fibrosis, CFTR, Molecular Chaperone, ENaC, Phenylbutyrate, Protein Trafficking.

Description of Research
I initially developed my interest in the molecular basis of drug action and my goal to design new drug threapies as an undergraduate at MIT, and began to hone this interest as a student in the Medical Scientist Training Program at UT-Southwestern. Building on the the biochemical techniques learned during my graduate training in molecular pharmacology and my clinical interest in Cystic Fibrosis, my primary research focus has been on basic (laboratory) and translational (clinical) studies of novel means to correct the dysfunction of mutant CFTR proteins. My initial in vitro work as a fellow demonstrated that sodium 4-phenylbutyrate (4PBA) improved the intracellular trafficking and function of the most common CFTR mutation in CF, ΔF508. These data led to our pilot clinical trial of 4PBA that demonstrated small improvments in ΔF508 function in people with CF. These data were a crucial proof of concept that havesupported larger efforts to identify correctors of ΔF508 traffikcing and function.

Our investigations into the mechanism(s) underlying this effect have focused on how 4PBA regulated molecular chaperones modulate the trafficking of CFTR in epithelial cells and other model systems. Because relative hyperfunction of the epithelial sodium channel (ENaC) is a characteristic feature of the CF airway, we have incresingly focused on how these 4PBA-regulated chaperones influence ENaC trafficking, as well as how CFTR itself may modulate ENaC traffikcing and function. Through these studies, my lab has gained significant expertise in molecular and physiologic techniques, including Ussing chambers, to study epithelial ion channel trafficking and function, as well as in the detection of CFTR and ENaC.

We have recently developed a keen mechanistic (laboratory) and translational (clinical) interest in Cystic Fibrosis Related Diabetes Mellitus (CFRD), which is an emerging clinical problem that increases morbidity and mortality in people with CF. The underlying basis of CFRD remains poorly understood, and we are beginning to apply things learned from our previous work to these problems as well.

Description of Itmat Expertise

Dr. Rubenstein focuses on novel, mutation-specific approaches to repair the function of mutant CFTR's in cystic fibrosis

Selected Publications

Sheikh Saba, Gudipaty Lalitha, De Leon Diva D, Hadjiliadis Denis, Kubrak Christina, Rosenfeld Nora K, Nyirjesy Sarah, Pelekis Amy, Malik Saloni, Stefanovski Darko, Cuchel Marina, Rubenstein Ronald C, Kelly Andrea, Rickels Michael R: Reduced β-Cell Secretory Capacity in Pancreatic Insufficient, But Not Pancreatic Sufficient, Cystic Fibrosis Despite Normal Glucose Tolerance. Diabetes 66: 134-144, January 2017.

Moss, RB, Flume, PA, Elborn, JS, Cooke, J, Rowe, SM, McColley, SA, Rubenstein, RC, Higgins, M on behalf of the VX11-770-110 (KONDUCT) Study Group: Efficacy and safety of ivacaftor in patients with cystic fibrosis who have an Arg117His-CFTR mutation: a double-blind, randomised controlled trial. Lancet Respir Med 3: 524-33, July 2015.

Conrad C, Lymp J, Thompson V, Dunn C, Davies Z, Chatfield B, Nichols D, Clancy J, Vender R, Egan M E, Quittell L, Michelson P, Antony V, Spahr J, Rubenstein R C, Moss R B, Herzenberg L A, Goss C H, Tirouvanziam R: Long-term treatment with oral N-acetylcysteine: Affects lung function but not sputum inflammation in cystic fibrosis subjects. A phase II randomized placebo-controlled trial. Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society 14(2): 219-227, 2015.

Sheikh, S, Putt, M, Forde, KA, Rubenstein, RC and Kelly A: Elevation of 1-Hour Plasma Glucose During Oral Glucose Tolerance Testing And Pulmonary Function in Cystic Fibrosis. Pediatr Pulmonol 50: 963-9, 2015.

Adams Kelly M, Abraham Valsamma, Spielman Daniel, Kolls Jay K, Rubenstein Ronald C, Conner Gregory E, Cohen Noam A, Kreindler James L: IL-17A Induces Pendrin Expression and Chloride-Bicarbonate Exchange in Human Bronchial Epithelial Cells. PloS one 9(8): e103263, 2014.

Grumbach Yael, Bikard Yann, Suaud Laurence, Chanoux Rebecca A, Rubenstein Ronald C: ERp29 Regulates Epithelial Sodium Channel Functional Expression by Promoting Channel Cleavage. American journal of physiology. Cell physiology 307(8): C701-9, 2014.

Sheikh Saba, Zemel Babette S, Stallings Virginia A, Rubenstein Ronald C, Kelly Andrea: Body composition and pulmonary function in cystic fibrosis. Frontiers in pediatrics 2: 33, 2014.

Millington, Kate, Miller, Victoria, Rubenstein, Ronald C., Kelly, Andrea: Patient and parent perceptions of the diagnosis and management of cystic fibrosis-related diabetes. Journal of Clinical & Translational Endocrinology. Elsevier, 1(3): 100-107, 2014.

Chanoux RA, Shubin CB, Robay A, Suaud L, Rubenstein RC.: Hsc70 negatively regulates epithelial sodium channel trafficking at multiple sites in epithelial cells. Am J Physiol Cell Physiol. 305: C776–C787, Oct 2013.

Clancy, J.P., Dupont, L., Konstan, M.W., Billings, J., Fustik, S., Goss, C.H., Lymp, J., Minic, P., Quittner, A.L,, Rubenstein, R.C., Young, K.R., Saiman, L., Burns, J.L., Govan, J.R., Ramsey, B. and Gupta, R, for the Arikace Study Group. : Phase II studies of nebulised Arikace in CF patients with Pseudomonas aeruginosa infection. Thorax 68(9): 818-25, Sep 2013.

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Last updated: 04/19/2017
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