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Ronald C. Rubenstein, MD, PhD
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Emeritus Professor of Pediatrics (Pulmonary Medicine)
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Department: Pediatrics
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Contact information
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Pulmonary Medicine and Cystic Fibrosis Center
c CHOP
21 Abramson Center Room 410A
3b 34th & CIVIC CENTER BLVD
Philadelphia, PA 19104
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c CHOP
21 Abramson Center Room 410A
3b 34th & CIVIC CENTER BLVD
Philadelphia, PA 19104
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Office: 215 590-1281
32 Fax: 215 590-1283
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32 Fax: 215 590-1283
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Publications
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Education:
21 9 S.B. 16 (Chemistry) c
3e Massachusetts Institute of Technology, 1984.
21 a Ph.D. 19 (Pharmacology) c
97 Medical Scientist Training Program, The University of Texas Southwestern Medical Center at Dallas, Southwestern Medical School, 1990.
21 9 M.D. c
97 Medical Scientist Training Program, The University of Texas Southwestern Medical Center at Dallas, Southwestern Medical School, 1991.
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Permanent link21 9 S.B. 16 (Chemistry) c
3e Massachusetts Institute of Technology, 1984.
21 a Ph.D. 19 (Pharmacology) c
97 Medical Scientist Training Program, The University of Texas Southwestern Medical Center at Dallas, Southwestern Medical School, 1990.
21 9 M.D. c
97 Medical Scientist Training Program, The University of Texas Southwestern Medical Center at Dallas, Southwestern Medical School, 1991.
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49 Pharmacologic repair of mutant CFTR function in Cystic Fibrosis.
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70 Key words: Cystic Fibrosis, CFTR, Molecular Chaperone, ENaC, Phenylbutyrate, Protein Trafficking.
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26 Description of Research
3f5 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.
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2d3 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.
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193 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.
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Description of Research Expertise
2b Research Interests49 Pharmacologic repair of mutant CFTR function in Cystic Fibrosis.
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70 Key words: Cystic Fibrosis, CFTR, Molecular Chaperone, ENaC, Phenylbutyrate, Protein Trafficking.
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26 Description of Research
3f5 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.
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2d3 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.
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193 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.
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d5 Zysman-Colman, Z.N.#, Kilberg, M.J.#, Harrison, V.S., Chesi, A., Grant, S.F.A., Mitchell, J., Sheikh, S., Hadjiliadis, D., Rickels, M.R., Rubenstein, R.C.* and Kelly, A. 26 #Equal Contributions as First Author db *Corresponding Author: Genetic Potential and Height Velocity during Childhood and Adolescence do not Fully Account for Shorter Stature in Cystic Fibrosis. Pediatr Res Page: in press, 2020.
78 Viviano, J.,* Brecker, M.,* Ferrara-Cook, C., Suaud, L. and Rubenstein, R.C. 91 * Equal Contribution as First Author: ERp29 as a Regulator of Insulin Biosynthesis. PLOS ONE Page: in press, 2020.
156 Hong, G., Alby, K., Ng, S.C.W., Fleck, V., Kubrak, C., Rubenstein, R.C., Dorgan, D.J., Kawut, S.M. and Hadjiliadis, D.: The Presence of Aspergillus fumigatus is Associated with Worse Respiratory Quality of Life in Cystic Fibrosis. J. Cystic Fibrosis 19: 125-130, 2020.
144 Kilberg, M., Sheikh, S., Stefanovski, D., Kubrak, C., DeLeon, D., Hadjiliadis, D., Rubenstein, R.C., Rickels, M.R. and Kelly, A.: Dysregulated Insulin in Pancreatic Insufficient Cystic Fibrosis with Post-Prandial Hypoglycemia. J. Cystic Fibrosis 2019.
16a Kelly, A., DeLeon, D.D., Sheikh, S., Camburn, D., Kubrak, C., Peleckis, A.J., Stefanovski, D., Hadjiliadis, D., Rickels, M.R. and Rubenstein, R.C.: Islet Hormone and Incretin Secretion in Cystic Fibrosis Following 4-months of Ivacaftor Therapy. Am. J. Resp. Crit. Care Med. 199: 342, 2019.
18a Nyirjesi, S.C., Sheikh, S., Hadjiliadis, D., DeLeon, D.D., Peleckis, A.J., Eiel, J.N., Kubrak, C., Stefanovski, D., Rubenstein, R.C., Rickels, M.R. and Kelly, A. : Beta-cell Secretory Defects are Present in Pancreatic Insufficient Cystic Fibrosis with 1-hour OGTT Glucose ≥155 mg/dL. J. Cystic Fibrosis 19: 1173, 2019.
a0 Bikard, Y.*, Viviano, J.*, Orr, M.N., Brown, L., Brecker, M., Jeger, J.L., Grits, D., Suaud, L. and Rubenstein, R.C. c2 *Equal contribution: The KDEL receptor has a role in the biogenesis and trafficking of the Epithelial Sodium Channel (ENaC). J. Biol. Chem. 294: 18324-18336, 2019.
193 Nyirjesi, S.C., Sheikh, S., Hadjiliadis, D., DeLeon, D.D., Peleckis, A.J., Eiel, J.N., Kubrak, C., Stefanovski, D., Rubenstein, R.C., Rickels, M.R. and Kelly, A. : Beta-cell Secretory Defects are Present in Pancreatic Insufficient Cystic Fibrosis with 1-hour OGTT Glucose ≥155 mg/dL. Pediatr. Diabetes Page: in press, May 2018.
160 Kazmerski, T.M., Sawicki, G.S., Miller, E., Jones, K.A.,Abebe, K.Z., Tuchman, L.K., Ladores, S., Rubenstein, R.C., Sagel, S.D., Weiner, D.J., Pilewski, J.M., Orenstein, D.O. and Borrero, S.: Sexual and reproductive health care utilization and preferences reported by young women with cystic fibrosis 44 J. Cystic Fibrosis 17: 64-70, January 2018.
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Selected Publications
f5 Sheikh, S., Localio, A.R., Kelly, A. and Rubenstein, R.C.: Cystic Fibrosis Related Diabetes and the 50-Gram Glucose Challenge Test. J. Cystic Fibrosis Page: in press, 2020.d5 Zysman-Colman, Z.N.#, Kilberg, M.J.#, Harrison, V.S., Chesi, A., Grant, S.F.A., Mitchell, J., Sheikh, S., Hadjiliadis, D., Rickels, M.R., Rubenstein, R.C.* and Kelly, A. 26 #Equal Contributions as First Author db *Corresponding Author: Genetic Potential and Height Velocity during Childhood and Adolescence do not Fully Account for Shorter Stature in Cystic Fibrosis. Pediatr Res Page: in press, 2020.
78 Viviano, J.,* Brecker, M.,* Ferrara-Cook, C., Suaud, L. and Rubenstein, R.C. 91 * Equal Contribution as First Author: ERp29 as a Regulator of Insulin Biosynthesis. PLOS ONE Page: in press, 2020.
156 Hong, G., Alby, K., Ng, S.C.W., Fleck, V., Kubrak, C., Rubenstein, R.C., Dorgan, D.J., Kawut, S.M. and Hadjiliadis, D.: The Presence of Aspergillus fumigatus is Associated with Worse Respiratory Quality of Life in Cystic Fibrosis. J. Cystic Fibrosis 19: 125-130, 2020.
144 Kilberg, M., Sheikh, S., Stefanovski, D., Kubrak, C., DeLeon, D., Hadjiliadis, D., Rubenstein, R.C., Rickels, M.R. and Kelly, A.: Dysregulated Insulin in Pancreatic Insufficient Cystic Fibrosis with Post-Prandial Hypoglycemia. J. Cystic Fibrosis 2019.
16a Kelly, A., DeLeon, D.D., Sheikh, S., Camburn, D., Kubrak, C., Peleckis, A.J., Stefanovski, D., Hadjiliadis, D., Rickels, M.R. and Rubenstein, R.C.: Islet Hormone and Incretin Secretion in Cystic Fibrosis Following 4-months of Ivacaftor Therapy. Am. J. Resp. Crit. Care Med. 199: 342, 2019.
18a Nyirjesi, S.C., Sheikh, S., Hadjiliadis, D., DeLeon, D.D., Peleckis, A.J., Eiel, J.N., Kubrak, C., Stefanovski, D., Rubenstein, R.C., Rickels, M.R. and Kelly, A. : Beta-cell Secretory Defects are Present in Pancreatic Insufficient Cystic Fibrosis with 1-hour OGTT Glucose ≥155 mg/dL. J. Cystic Fibrosis 19: 1173, 2019.
a0 Bikard, Y.*, Viviano, J.*, Orr, M.N., Brown, L., Brecker, M., Jeger, J.L., Grits, D., Suaud, L. and Rubenstein, R.C. c2 *Equal contribution: The KDEL receptor has a role in the biogenesis and trafficking of the Epithelial Sodium Channel (ENaC). J. Biol. Chem. 294: 18324-18336, 2019.
193 Nyirjesi, S.C., Sheikh, S., Hadjiliadis, D., DeLeon, D.D., Peleckis, A.J., Eiel, J.N., Kubrak, C., Stefanovski, D., Rubenstein, R.C., Rickels, M.R. and Kelly, A. : Beta-cell Secretory Defects are Present in Pancreatic Insufficient Cystic Fibrosis with 1-hour OGTT Glucose ≥155 mg/dL. Pediatr. Diabetes Page: in press, May 2018.
160 Kazmerski, T.M., Sawicki, G.S., Miller, E., Jones, K.A.,Abebe, K.Z., Tuchman, L.K., Ladores, S., Rubenstein, R.C., Sagel, S.D., Weiner, D.J., Pilewski, J.M., Orenstein, D.O. and Borrero, S.: Sexual and reproductive health care utilization and preferences reported by young women with cystic fibrosis 44 J. Cystic Fibrosis 17: 64-70, January 2018.
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