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Pamela D. Davis, Ph.D.
Professor
pbd@case.edu
(216) 368 4370 Phone
(216) 368 4223 Fax
Biography
Dr. Davis is the Arline H. and Curtis F. Garvin Research Professor at Case Western Reserve University , the Chief of the Pediatric Pulmonary Division at Rainbow Babies and Childrens’ Hospital, and Professor of Pediatrics, Physiology & Biophysics, and Molecular Biology & Microbiology at Case Western Reserve University , and Senior Associate Dean for Research at the School of Medicine . She received the A. B. degree summa cum laude from Smith College , Northampton , MA , and the M.D. and Ph.D. degrees from Duke University . After completing an internship and residency in Medicine at Duke Hospital , she became a Clinical Associate in the Pediatric Metabolism Branch of NIDDK (then NIAMDD) where she received fellowship training in Pulmonary Medicine (via the NHLBI). In 1981, she moved to Case Western Reserve University where she rose through the ranks to her current position. Dr. Davis directs the Willard A. Bernbaum Cystic Fibrosis Research Center at Case Western Reserve University , which is the site of a Core Center from NIDDK and a Research Development Center for the Cystic Fibrosis Foundation. Dr. Davis has published more than 120 original articles, mostly in the area of cystic fibrosis research, edited one book, contributed numerous book chapters, and served as Associate Editor for several journals. She holds seven U.S. Patents, is a founding scientist of Copernicus Therapeutics, Inc, and serves on the Scientific Advisory Board of Arizeke, Inc, to which some of her patents are licensed. She has served on the Advisory Council to NIDDK, on the Board of Scientific Counselors for NHLBI, and on advisory boards for the Burroughs Wellcome Fund and several academic cystic fibrosis centers. She is the recipient of the Rosenthal Prize for academic pediatrics, the Smith College Medal, and has been named regularly in Best Doctors in America and Top Doctors. She was inducted into the Cleveland Medical Hall of Fame. Her major research interest is in cystic fibrosis, specifically the structure and function of the CFTR molecule, how the cystic fibrosis lung disease arises, and strategies for gene therapy of cystic fibrosis. The interest in the CF lung disease has broadened into a more general interest in lung inflammation, and the strategies she has developed for gene therapy of CF now seem applicable to a broader range of human disease as well.
Research Interests
Dr. Davis has focused on understanding and treating the lung disease of cystic fibrosis (CF). One of her first novel and important contributions was a new approach for treating the CF lung disease by limiting the excessive inflammatory response. In a four-year double-blind, placebo-controlled trial, she showed that high dose ibuprofen dramatically retards progression of the CF lung disease. This remains the only treatment directly demonstrated to alter disease progression. Since that time she has studied the mechanisms that lead from the defective CF gene to the excess inflammatory response, with the goal of identifying alternative anti-inflammatory treatments. A second line of work has focused on correcting the CF defect at its source – the defective gene. She has devised a novel, safe, and effective method of non-viral gene delivery to airway epithelium. Compacted DNA enters airway epithelial cells, accesses the nucleus, and is expressed, and is safe and non-immunogenic, critical features for a vector that must be administered over a lifetime. She has developed both receptor-targeted and non-targeted vectors, the latter of which recently came to successful Phase I clinical trial in nasal epithelium of patients with CF, demonstrating no adverse effects and some correction of the ion transport defect. Studies of receptor targeting also led to the development of targeted therapeutics which access the airway epithelium via a transcytotic receptor. A protein that targets the polymeric immunoglobulin receptor, fused to a therapeutic protein, delivers the payload directly to the apical surface of the epithelium, beneath the mucus layer, in both cell and in vivo model systems. In addition, she has investigated the physiologic consequences of CFTR dysfunction and identified the genes that malfunction in CF. One of them, FXYD5, is little-studied but may be important in the transport of sodium in the lung, and the lab is pursuing this possibility.
Publications
van Heeckeren AM, Schluchter MD, Xue W, Davis PB.
"Response to Acute Lung Infection with Mucoid Pseudomonas aeruginosa in Cystic Fibrosis Mice"
Am J Respir Crit Care Med. 2005 Nov 4
Rhea M, Davis PB.
"Mechanism of uptake of C105Y-a novel cell penetrating peptide"
J Biol Chem. 2005 Nov 4
Davis PB
"Cystic Fibrosis Since 1938"
Am J Respir Crit Care Med. 2005 Aug 26
Kube DM, Fletcher D, Davis PB
Relation of exaggerated cytokine responses of CF airway epithelial cells to PAO1 adherence
Respir Res. 2005 Jul 11;6(1):69
Gupta S, Heacock M, Perez A, Davis PB
“Antiboides to the polymeric immunoglobulin receptor with different binding and trafficking patterns”
Am J Respir Cell Mol Biol. 2005 Jun 30
Konstan MW, Davis PB, Wagener JS, Hilliard KA, Stern RC, Milgram LJ, Kowalczyk TH, Hyatt SL, Fink TL, Gedeon CR, Oette SM, Payne JM, Muhammad O, Ziady AG, Moen RC, Cooper MJ
"Compacted DNA nanoparticles administered to the nasal mucosa of cystic fibrosis subjects are safe and demonstrate partial to complete cystic fibrosis transmembrane regulator reconstitution"
Hum Gene Ther. 15(12):1255-69, 2004
Davis PB, Drumm ML
"Some like it hot: curcumin and CFTR"
Trends Mol Med. 10(10):473-5, 2004
Davis PB, Schluchter MD, Konstan MW
"Relation of sweat chloride concentration to severity of lung disease in cystic fibrosis"
Pediatr Pulmonol. 38(3):204-9, 2004
Ziady AG, Kim J, Colla J, Davis PB
"Defining strategies to extend duration of gene expression from targeted compacted DNA vectors"
Gene Ther. 11(18):1378-90, 2004
Perez A, Davis PB
"Gene profile changes after Pseudomonas aeruginosa exposure in immortalized airway epithelial cells"
J Struct Funct Genomics. 5(3):179-94, 2004
Van Heeckeren AM, Schluchter MD, Drumm ML, Davis PB
"Role of Cftr genotype in the response to chronic Pseudomonas aeruginosa lung infection in mice"
Am J Physiol Lung Cell Mol Physiol. 287(5), 2004
Van Heeckeren AM, Schluchter M, Xue L, Alvarez J, Freedman S, St George J, Davis PB
"Nutritional effects on host response to lung infections with mucoid Pseudomonas aeruginosa in mice"
Infect Immun. 72(3):1479-86, 2004
Ziady AG, Gedeon CR, Muhammad O, Stillwell V, Oette SM, Fink TL, Quan W, Kowalczyk TH, Hyatt SL, Payne J, Peischl A, Seng JE, Moen RC, Cooper MJ, Davis PB
"Minimal toxicity of stabilized compacted DNA nanoparticles in the murine lung"
Mol Ther. 8(6):948-56, 2003
Ziady AG, Gedeon CR, Miller T, Quan W, Payne JM, Hyatt SL, Fink TL, Muhammad O, Oette S, Kowalczyk T, Pasumarthy MK, Moen RC, Cooper MJ, Davis PB
"Transfection of airway epithelium by stable PEGylated poly-L-lysine DNA nanoparticles in vivo"
Mol Ther. 8(6):936-47, 2003
Van Heeckeren AM, Scaria A, Schluchter MD, Ferkol TW, Wadsworth S, Davis PB
"Delivery of CFTR by adenoviral vector to cystic fibrosis mouse lung in a model of chronic Pseudomonas aeruginosa lung infection"
Am J Physiol Lung Cell Mol Physiol. 2004 Apr;286(4):L717-26.
Gupta S, Xie J, Ma J, Davis PB
"Intermolecular interaction between R domains of cystic fibrosis transmembrane conductance regulator"
Am J Respir Cell Mol Biol. 30(2):242-8, 2004
Chmiel JF, Davis PB
"State of the Art: Why do the lungs of patients with cystic fibrosis become infected and why can't they clear the infection?"
Respir Res. 27;4(1):8, 2003
Konstan MW, Krenicky JE, Finney MR, Kirchner HL, Hilliard KA, Hilliard JB, Davis PB, Hoppel CL
"Effect of ibuprofen on neutrophil migration in vivo in cystic fibrosis and healthy subjects"
J Pharmacol Exp Ther. 306(3):1086-91, 2003
A.G. Ziady, P.B. Davis, and M.W. Konstan
"Novel non-viral gene transfer therapy for cystic fibrosis"
Expert Opinion on Biological Therapy. 3:449-458, 2003
Konstan MW, Davis PB
"Pharmacological approaches for the discovery and development of new anti-inflammatory agents for the treatment of cystic fibrosis"
Adv Drug Deliv Rev. 54(11):1409-23, 2002
Schluchter MD, Konstan MW, Davis PB
"Jointly modelling the relationship between survival and pulmonary function in cystic fibrosis patients"
Stat Med. 21(9):1271-87, 2002
Xie J, Adams LM, Zhao J, Gerken TA, Davis PB, Ma J
"A short segment of the R domain of cystic fibrosis transmembrane conductance regulator contains channel stimulatory and inhibitory activities that are separable by sequence modification"
J Biol Chem. 277(25):23019-27, 2002
Ziady AG, Kelley TJ, Milliken E, Ferkol T, Davis PB
"Functional evidence of CFTR gene transfer in nasal epithelium of cystic fibrosis mice in vivo following luminal application of DNA complexes targeted to the serpin-enzyme complex receptor"
Molecular Therapy 5(4):413-9, 2002
Hilliard JB, Konstan MW, Davis PB
"Inflammatory mediators in CF patients"
Methods Mol Med. 70:409-31, 2002
Gupta S, Eastman J, Silski C, Ferkol T, Davis PB
"Single chain Fv: a ligand in receptor-mediated gene delivery"
Gene Ther. 8(8):586-92, 2001
Kube D, Sontich U, Fletcher D, Davis PB
"Proinflammatory cytokine responses to P. aeruginosa infection in human airway epithelial cell lines"
Am J Physiol Lung Cell Mol Physiol. 280(3):L493-502, 2001
Kube D, Adams L, Perez A, Davis PB
"Terminal sialylation is altered in airway cells with impaired CFTR-mediated chloride transport"
Am J Physiol Lung Cell Mol Physiol. 280(3):L482-92, 2001
Xie J, Zhao J, Davis PB, Ma J.
"Conformation, independent of charge, in the R domain affects cystic fibrosis transmembrane conductance regulator channel openings"
Biophys J. 78(3):1293-305, 2000
van Heeckeren AM, Tscheikuna J, Walenga RW, Konstan MW, Davis PB, Erokwu B, Haxhiu MA, Ferkol TW
"Effect of Pseudomonas infection on weight loss, lung mechanics, and cytokines in mice"
Am J Respir Crit Care Med. 161(1):271-9, 2000
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