Research Topics
Genomes and Genes | Pamela L ZeitlinSummaryAffiliation: Johns Hopkins University Country: USA Publications
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Publications
Emerging drug treatments for cystic fibrosisPamela L Zeitlin
Park 316, Department of Pediatrics, Johns Hopkins Hospital, 600 N Wolfe St, Baltimore, MD 21209, USA
Expert Opin Emerg Drugs 8:523-35. 2003..High-throughput screening, pharmacogenomics and proteomics bring recent technological advances to the field...- Emerging drug treatments for cystic fibrosisPamela L Zeitlin
The John Hopkins School of Medicine, Department of Pediatrics, Children s Health Building, 200 N Wolfe St, Baltimore, MD 21287, USA
Expert Opin Emerg Drugs 12:329-36. 2007..Partnership between large and small pharma, the Cystic Fibrosis Foundation and academia should be fostered to accelerate therapeutic development... - Is it go or NO go for S-nitrosylation modification-based therapies of cystic fibrosis transmembrane regulator trafficking?Pamela L Zeitlin
Department of Pediatrics, Eudowood Division of Pediatric Respiratory Sciences, The Johns Hopkins School of Medicine, Park 316, 600 N Wolfe St, Baltimore, MD 21287, USA
Mol Pharmacol 70:1155-8. 2006.... - A phase I trial of intranasal Moli1901 for cystic fibrosisPamela L Zeitlin
Departments of Pediatrics, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
Chest 125:143-9. 2004..The peptide drug Moli1901 activates an alternative chloride channel that is present in cystic fibrosis (CF) nasal and airway epithelia. Doing so bypasses the dysfunctional CF transmembrane regulator... 
Cystic fibrosis and estrogens: a perfect stormPamela L Zeitlin
Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA
J Clin Invest 118:3841-4. 2008..The authors suggest that these data warrant the testing of antiestrogen therapy in females with CF and propose an alternative avenue for CF therapeutic development...- Lubiprostone activates non-CFTR-dependent respiratory epithelial chloride secretion in cystic fibrosis miceKelvin D MacDonald
Eudowood Division of Pediatric Respiratory Sciences, Johns Hopkins Medical Institutions, 200 N Wolfe Street, Baltimore, MD 21287, USA
Am J Physiol Lung Cell Mol Physiol 295:L933-40. 2008..RT-PCR confirmed expression of ClC-2 mRNA in murine lung homogenate. The direct application of lubiprostone in the CF murine nasal airway restores nearly normal levels of chloride secretion in nasal epithelia... 
Spiperone, identified through compound screening, activates calcium-dependent chloride secretion in the airwayLihua Liang
Department of Physiology, Johns Hopkins University School of Medicine, 725 N Wolfe St, Baltimore, MD 21205, USA
Am J Physiol Cell Physiol 296:C131-41. 2009..In conclusion, we have identified spiperone as a new therapeutic platform for correction of defective Cl(-) secretion in CF via a pathway independent of CFTR...- Patients with mutations in Gsalpha have reduced activation of a downstream target in epithelial tissues due to haploinsufficiencyStephanie C Hsu
Department of Pediatric Endocrinology, Johns Hopkins University, 733 North Broadway, Suite 551, Baltimore, Maryland 21205, USA
J Clin Endocrinol Metab 92:3941-8. 2007..The mechanism by which these mutations lead to the AHO phenotype has been difficult to establish due to the inaccessibility of the affected tissues... - Chemical rescue of deltaF508-CFTR mimics genetic repair in cystic fibrosis bronchial epithelial cellsOm V Singh
Department of Pediatrics, The Johns Hopkins School of Medicine, Baltimore, Maryland 21287, USA
Mol Cell Proteomics 7:1099-110. 2008..We conclude that chemically rescued CFTR associates with a specific set of HSP70 family proteins that mark therapeutic interactions and can be useful to correct both ion transport and inflammatory phenotypes in CF subjects... - Repeated aerosolized AAV-CFTR for treatment of cystic fibrosis: a randomized placebo-controlled phase 2B trialRichard B Moss
Department of Pediatrics, Stanford University, Stanford, CA 94305, and Division of Respiratory Diseases, Children s Hospital Boston, MA 02115, USA
Hum Gene Ther 18:726-32. 2007..Because gene transfer is the simplest, most basic way to correct the underlying genetic defect that leads to disease in CF, further research is warranted to develop an effective gene transfer agent for the treatment of CF... - Pharmacoproteomics of 4-phenylbutyrate-treated IB3-1 cystic fibrosis bronchial epithelial cellsOm V Singh
Department of Pediatrics, The Johns Hopkins School of Medicine, Baltimore, Maryland 21209, USA
J Proteome Res 5:562-71. 2006..Subsets of these proteins were confirmed by immunoblot analysis. These data represent a first-draft of the pharmacoproteomics map of 4-PBA treated cystic fibrosis bronchial epithelial cells... - N-acetylcysteine enhances cystic fibrosis sputum penetration and airway gene transfer by highly compacted DNA nanoparticlesJung Soo Suk
Department of Ophthalmology, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21231, USA
Mol Ther 19:1981-9. 2011..Our findings suggest that a promising synthetic nanoparticle gene carrier may transfer genes substantially more effectively to lungs of CF patients if administered following adjuvant mucolytic therapy with NAC or NAC + rhDNase... - Membrane-associated heparan sulfate is not required for rAAV-2 infection of human respiratory epitheliaMichael P Boyle
Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore MD 21205, USA
Virol J 3:29. 2006..The aim of this investigation was to determine the necessity of cell membrane HSPG for efficient infection by rAAV-2... - Levofloxacin pharmacokinetics in adult cystic fibrosisCarlton K K Lee
Pediatrics, Pediatric Infectious Diseases, Johns Hopkins University, 600 North Wolfe St, Carnegie 180, Baltimore, MD 21287 6180, USA
Chest 131:796-802. 2007..We studied the preliminary pharmacokinetic and pharmacodynamic (PK/PD) relationship of levofloxacin in CF... - Ubiquitin C-terminal hydrolase-L1 protects cystic fibrosis transmembrane conductance regulator from early stages of proteasomal degradationMark J Henderson
Department of Pediatrics, Johns Hopkins School of Medicine, Baltimore, Maryland 21287, USA
J Biol Chem 285:11314-25. 2010..Although not sufficient by itself to rescue mutant CFTR therapeutically, the elevation of UCH-L1 and its effect on CFTR processing provides insight into its potential roles in CF and other diseases... - Correlation between DNA transfer and cystic fibrosis airway epithelial cell correction after recombinant adeno-associated virus serotype 2 gene therapyTerence R Flotte
Department of Pediatrics, University of Florida, Gainesville, 32610, USA
Hum Gene Ther 16:921-8. 2005..The observation of sizeable physiological correction in the face of low mRNA levels may reflect the regulatory role of low levels of CFTR protein as an activator of other chloride channels... - Repeated adeno-associated virus serotype 2 aerosol-mediated cystic fibrosis transmembrane regulator gene transfer to the lungs of patients with cystic fibrosis: a multicenter, double-blind, placebo-controlled trialRichard B Moss
Department of Pediatrics, Stanford University, Stanford, CA, USA
Chest 125:509-21. 2004..CONCLUSIONS: Repeat doses of aerosolized tgAAVCF were safe and well tolerated, and resulted in encouraging trends in improvement in pulmonary function in patients with CF and mild lung disease... - CHOP transcription factor mediates IL-8 signaling in cystic fibrosis bronchial epithelial cellsNeeraj Vij
Division of Pediatric Respiratory Sciences, Johns Hopkins School of Medicine, 200 N Wolfe St, Baltimore, MD 21287, USA
Am J Respir Cell Mol Biol 38:176-84. 2008..We confirmed the regulation of IL-8 promoter by CHOP in CF cells using the IL-8 reporter assay. We conclude that PGE-2 stimulates IL-8 production through the CHOP transcription factor in CF cells... - Modulation of deltaF508 cystic fibrosis transmembrane regulator trafficking and function with 4-phenylbutyrate and flavonoidsMeerana Lim
Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA
Am J Respir Cell Mol Biol 31:351-7. 2004..Thus, a combination of chronic treatment with 4-PBA or select flavonoids, followed by acute flavonoid exposure, may be beneficial in cystic fibrosis... - Modulation of Sp1 and Sp3 in lung epithelial cells regulates ClC-2 chloride channel expressionKathryn W Holmes
Eudowood Division of Pediatric Respiratory Sciences, The Johns Hopkins Medical Institutions, 600 N Wolfe St. Park 316, Baltimore, MD 21287-2533, USA
Am J Respir Cell Mol Biol 29:499-505. 2003..These experiments suggest that the mechanism for postnatal reduction of ClC-2 expression in lung epithelia is based on decreased interaction of Sp1 and Sp3 with the ClC-2 promoter... - Positive expiratory pressure changes aerosol distribution in patients with cystic fibrosisBeth L Laube
Department of Pediatrics, Johns Hopkins University, Baltimore, Maryland 21287 2533, USA
Respir Care 50:1438-44. 2005..We hypothesized that aerosol distribution in the lungs of patients with cystic fibrosis changes with positive expiratory pressure (PEP)... - Gene expression profile analysis of 4-phenylbutyrate treatment of IB3-1 bronchial epithelial cell line demonstrates a major influence on heat-shock proteinsJerry M Wright
Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA
Physiol Genomics 16:204-11. 2004..Our results demonstrate the usefulness of gene expression profile analysis in understanding the consequences of PBA treatment and provide insights in how this drug exerts its effect on the trafficking of CFTR... - Regulation of the ClC-2 lung epithelial chloride channel by glycosylation of SP1Neeraj Vij
Eudowood Division of Pediatric Respiratory Sciences, Department of Pediatrics, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
Am J Respir Cell Mol Biol 34:754-9. 2006..Our results support the hypothesis that glycosylation of SP1 produces the 105-kD isoform of SP1 and is involved in regulating ClC-2 gene expression... - Selective inhibition of endoplasmic reticulum-associated degradation rescues DeltaF508-cystic fibrosis transmembrane regulator and suppresses interleukin-8 levels: therapeutic implicationsNeeraj Vij
Division of Pediatric Respiratory Sciences, Johns Hopkins School of Medicine, Baltimore, Maryland 21287, USA
J Biol Chem 281:17369-78. 2006..We conclude that VCP is an integral component of ERAD and cellular stress pathways induced by the unfolded protein response and may be central to the efficacy of CF drugs that target the ubiquitin-proteasome pathway... - CFTR is a negative regulator of NFkappaB mediated innate immune responseNeeraj Vij
Department of Pediatric Respiratory Sciences, The Johns Hopkins School of Medicine, Baltimore, Maryland, United States of America
PLoS ONE 4:e4664. 2009..The mechanism(s) by which CFTR mediates inflammatory signaling is under debate... - Evidence of CFTR function in cystic fibrosis after systemic administration of 4-phenylbutyratePamela L Zeitlin
Departments of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA
Mol Ther 6:119-26. 2002..This short-term phase I/II study demonstrates proof of principle that modulation of deltaF508 CFTR biosynthesis and trafficking is a viable therapeutic approach for cystic fibrosis... - Inflammatory and microbiologic markers in induced sputum after intravenous antibiotics in cystic fibrosisClaudia L Ordonez
Department of Pediatrics, Harvard Medical School, Boston, MA 02215, USA
Am J Respir Crit Care Med 168:1471-5. 2003..Seven of 127 (6%) sputum induction procedures showed a decrease in FEV1 of 20% or more. We conclude that markers in induced sputum may be useful, noninvasive outcome measures to assess response to therapies in cystic fibrosis studies... - Respiratory epithelial gene expression in patients with mild and severe cystic fibrosis lung diseaseJerry M Wright
Department of Physiology, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
Am J Respir Cell Mol Biol 35:327-36. 2006.... - Applications of proteomic technologies for understanding the premature proteolysis of CFTRMark J Henderson
Department of Pediatrics, Johns Hopkins School of Medicine, Baltimore, MD 21287, USA
Expert Rev Proteomics 7:473-86. 2010..Additionally, we emphasize the potential for proteomic-based technologies in expanding our understanding of CF pathophysiology and therapeutic approaches... - Atypical cystic fibrosis and CFTR-related diseasesShruti M Paranjape
Eudowood Division of Pediatric Respiratory Sciences, The Johns Hopkins University, David M Rubenstein Child Health Building, 200 North Wolfe Street, Baltimore, MD 21287, USA
Clin Rev Allergy Immunol 35:116-23. 2008.... - Effect of adeno-associated virus-specific immunoglobulin G in human amniotic fluid on gene transferMichael P Boyle
Department of Medicine, The Johns Hopkins University School of Medicine, Jefferson B1 170, 600 North Wolfe Street, Baltimore, MD 21287 8922, USA
Hum Gene Ther 14:365-73. 2003..These studies demonstrate that AF from some individuals contains AAV-specific IgG that can inhibit gene transfer... - Acidic pH hyperpolarizes nasal potential differenceOmotola Uwaifo
Department of Pediatrics, University of Maryland School of Medicine, Baltimore, Maryland, USA
Pediatr Pulmonol 41:151-7. 2006..Acidic pH stimulated NPD responses in 33% of subjects. These findings suggest that pH sensitive alternative pathways are available for modulation in human respiratory epithelia and that NPD protocols should standardize pH of perfusates... - Therapeutic approaches to repair defects in deltaF508 CFTR folding and cellular targetingKristina Powell
The Johns Hopkins University School of Medicine, 316 Johns Hopkins Hospital, 600 N Wolfe St, Baltimore, MD 21287, USA
Adv Drug Deliv Rev 54:1395-408. 2002..This paper focuses on the events that occur in the ER during folding and reviews potential targets for therapeutic intervention... - Safety and tolerability of denufosol tetrasodium inhalation solution, a novel P2Y2 receptor agonist: results of a phase 1/phase 2 multicenter study in mild to moderate cystic fibrosisRobin Deterding
Department of Pediatrics, Children s Hospital, Denver, Colorado 80218, USA
Pediatr Pulmonol 39:339-48. 2005..recently completed a multicenter, 28-day, phase 2 safety and efficacy clinical trial of denufosol inhalation solution in CF subjects with mild lung disease... - Transient effectiveness of vitamin D2 therapy in pediatric cystic fibrosis patientsDeanna M Green
Eudowood Division of Pediatric Respiratory Sciences, The Johns Hopkins Medical Institutions, Baltimore, MD 21287, USA
J Cyst Fibros 9:143-9. 2010..The effectiveness of current treatment recommendations for vitamin D insufficiency in children with CF is unknown. Therefore, we assessed the effectiveness of vitamin D(2) 50,000 IU once daily for 28 days for vitamin D insufficiency... - Variant cystic fibrosis phenotypes in the absence of CFTR mutationsJoshua D Groman
McKusick Nathans Institute of Genetic Medicine and Cystic Fibrosis Foundation Genotyping Center, Johns Hopkins University School of Medicine, Baltimore, USA
N Engl J Med 347:401-7. 2002..We assessed whether alteration in CFTR function is responsible for the entire spectrum of variant cystic fibrosis phenotypes... - Protein processing and degradation in pulmonary health and diseasePamela L Zeitlin
Department of Pediatrics, John Hopkins School of Medicine, Baltimore, MD 20892, USA
Am J Respir Cell Mol Biol 29:642-5. 2003 - Proteome of synaptosome-associated proteins in spinal cord dorsal horn after peripheral nerve injuryOm V Singh
Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Proteomics 9:1241-53. 2009..These changes might participate in the central mechanism that underlies the maintenance of neuropathic pain... - The penetration of fresh undiluted sputum expectorated by cystic fibrosis patients by non-adhesive polymer nanoparticlesJung Soo Suk
Department of Biomedical Engineering, The Johns Hopkins University School of Medicine, 720 Rutland Avenue, Baltimore, MD 21205, USA
Biomaterials 30:2591-7. 2009..The results also offer hope that desperately needed sputum-penetrating drug- and gene-carrier nanoparticles can be developed for CF... - Cystic fibrosis transmembrane regulator protein mutations: 'class' opportunity for novel drug innovationKelvin D MacDonald
Johns Hopkins University School of Medicine, Eudowood Division of Pediatric Respiratory Sciences, Baltimore, Maryland, USA
Paediatr Drugs 9:1-10. 2007..Questions regarding the amount of CFTR correction needed, delivery methods, and optimal therapeutic combinations, however, remain outstanding... - Cystic fibrosis and sinusitis in children: outcomes and socioeconomic statusLara C Kovell
Department of Otolaryngology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
Otolaryngol Head Neck Surg 145:146-53. 2011..The investigators evaluated the impact of surgery and SES on pulmonary function tests (PFTs) in children with CF and rhinosinusitis... - cis-Acting elements within CFTR 5'-flanking DNA are not sufficient to decrease gene expression in response to phorbol esterPeter J Mogayzel
Eudowood Division of Pediatric Respiratory Sciences, The Johns Hopkins Medical Institutions, 600 North Wolfe Street, Park 316, Baltimore, MD 21287 2533, USA
Biochim Biophys Acta 1576:306-15. 2002.... - Dual activation of CFTR and CLCN2 by lubiprostone in murine nasal epitheliaEric S Schiffhauer
Department of Pediatrics, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
Am J Physiol Lung Cell Mol Physiol 304:L324-31. 2013..The utilization of CLCN2 as an alternative chloride efflux channel could provide clinical benefit to patients with CF, especially if the pharmacological activator is administered as an aerosol... - Significant microbiological effect of inhaled tobramycin in young children with cystic fibrosisRonald L Gibson
Department of Pediatrics, Children s Hospital and Regional Medical Center University of Washington, Seattle, Washington 98105 0371, USA
Am J Respir Crit Care Med 167:841-9. 2003..We conclude that 28 days of tobramycin solution for inhalation of 300 mg twice daily is safe and effective for significant reduction of lower airway Pa density in young children with cystic fibrosis... - ClC-5: ontogeny of an alternative chloride channel in respiratory epitheliaRebecca D Edmonds
Department of Pediatrics, Eudowood Division of Respiratory Sciences, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
Am J Physiol Lung Cell Mol Physiol 282:L501-7. 2002..In addition, the manipulation of non-CFTR chloride channels may provide a viable approach for treating cystic fibrosis lung disease... - Phase I trial of intranasal and endobronchial administration of a recombinant adeno-associated virus serotype 2 (rAAV2)-CFTR vector in adult cystic fibrosis patients: a two-part clinical studyTerence R Flotte
Department of Pediatrics and Powell Gene Therapy Center, University of Florida, Gainesville, FL 32610 0296, USA
Hum Gene Ther 14:1079-88. 2003..These data indicate the need for continued evaluation of rAAV-CFTR vectors in additional clinical trials... - Standardized procedure for measurement of nasal potential difference: an outcome measure in multicenter cystic fibrosis clinical trialsThomas A Standaert
University of Washington, Seattle, Washington, USA
Pediatr Pulmonol 37:385-92. 2004..Valid and consistent results can be attained with trained operators and attention to technical details. These data demonstrate the procedure to be sufficient for multicenter studies in the CF Foundation network... - Evaluation of exposure and health care worker response to nebulized administration of tgAAVCF to patients with cystic fibrosisGerry A Croteau
University of Washington, Department of Environmental and Occupational Health Sciences, Field Research and Consultation Group, 4225 Roosevelt Way NE, Suite 100, Seattle, WA 98105 6099, USA
Ann Occup Hyg 48:673-81. 2004..0006% of the administered dose. At this level of exposure, the prevalence of symptoms was very low, the spectrum was similar in both study groups and did not result in any reported negative health effects... - Down-regulation of IL-8 expression in human airway epithelial cells through helper-dependent adenoviral-mediated RNA interferenceHui Bi Cao
Programme in Lung Biology Research and the Canadian Institutes of Health Research Group in Lung Development, Hospital for Sick Children, Toronto, Canada M5G 1X8
Cell Res 15:111-9. 2005.... - Dietary supplement use in pediatric patients with cystic fibrosisKara L Murray
Department of Pharmacy, Centennial Medical Center, Nashville, TN 37203, USA
Am J Health Syst Pharm 65:562-5. 2008..The use of dietary supplements and their perceived effectiveness in pediatric patients with cystic fibrosis (CF) were studied... - Serum proteomic signature for cystic fibrosis using an antibody microarray platformMeera Srivastava
Department of Anatomy, Physiology and Genetics, Uniformed Services University School of Medicine, USUHS, Bethesda, MD 20814, USA
Mol Genet Metab 87:303-10. 2006..We conclude that antibody microarray technology is sensitive, quantitative, and robust, and can be useful as a proteomic platform to discriminate between sera from CF and control patients... - Variants in mannose-binding lectin and tumour necrosis factor alpha affect survival in cystic fibrosisKitti Buranawuti
McKusick Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine Baltimore, Maryland, USA
J Med Genet 44:209-14. 2007..Patients with cystic fibrosis with the same mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene differ widely in survival suggesting other factors have a substantial role in mortality... - De novo biosynthetic profiling of high abundance proteins in cystic fibrosis lung epithelial cellsHarvey B Pollard
Department of Anatomy, Physiology and Genetics, Uniformed Services University School of Medicine, Bethesda, Maryland 20814, USA
Mol Cell Proteomics 5:1628-37. 2006..We anticipate that this novel hybrid approach to discovery of the high abundance CF proteome will find general application to other proteomic problems in biology and medicine...
Research Grants
- CHLORIDE CHANNELS IN LUNG DEVELOPMENTPamela L Zeitlin; Fiscal Year: 2010..The product of this work will be a method of stimulating chloride transport to compensate for mutant CFTR, reduce sodium absorption and relieve airway inflammation in vivo. ..
- CHLORIDE CHANNELS IN LUNG DEVELOPMENTPamela Zeitlin; Fiscal Year: 2009..The product of this work will be a method of stimulating chloride transport to compensate for mutant CFTR, reduce sodium absorption and relieve airway inflammation in vivo. ..
- Multidisciplinary Training Program in Pediatric Pulmona*Pamela Zeitlin; Fiscal Year: 2007..Minority Advisory Comm. & External Advisory Comm. The existing training program has been highly successful & this high performance standard will be applied to the proposed expansion program. ..
- CHLORIDE CHANNELS IN LUNG DEVELOPMENTPamela Zeitlin; Fiscal Year: 2007..Combining the hClC-2 TET-On model with the CF knockout will be the approach for the second hypothesis that CF might be treated by over-expression of hClC-2. ..
- CHLORIDE CHANNELS IN LUNG DEVELOPMENTPamela Zeitlin; Fiscal Year: 2002....
- CHLORIDE CHANNELS IN LUNG DEVELOPMENTPamela Zeitlin; Fiscal Year: 2009..The product of this work will be a method of stimulating chloride transport to compensate for mutant CFTR, reduce sodium absorption and relieve airway inflammation in vivo. ..