Bacterial Infections; Cystic Fibrosis; Epithelial Cells; Genetic Code; Immunity, Innate; Inflammation; Lung; Macrophages; Microbiology; Pediatrics; Physiology; Pseudomonas aeruginosa; Clinical Trial; Macrophages, Alveolar; Cystic Fibrosis Transmembrane Conductance Regulator; Adaptive Immunity; Airway Management
Cellular & Molecular Physiology: Epithelial Transport of Ions and Solutes | Membrane Protein Sorting and Trafficking | Membrane Proteins - Ion Channels | Physiology of Human Disease
Stem Cells and Tissue Repair
Dr. Egan’s primary research interest is to understand the regulation of ion transport across the airway epithelia in health and disease. Transepithelial ion transport is responsible for maintaining the airway surface fluid, i.e. the periciliary fluid layer, which controls mucociliary clearance. Abnormalities in the ion channels and regulators of these channels can alter mucociliary clearance, leading to retained secretions, mucus plugging, infection, and lung destruction, as seen in cystic fibrosis. In CF, it is the abnormal function of the cystic fibrosis transmembrane conductance regulator (CFTR), a multifunctional protein encoded by the gene that is affected in cystic fibrosis (CF) that underlies the abnormal ion transport in affected organs.
The Egan lab uses a variety of electrophysiologic techniques to examine how CFTR expression affects transepithelial ion transport in airway epithelial cells. They have shown that CFTR can modulate other ion channels and, as its name implies, act as a conductance regulator. In addition, they have been very interested in understanding and identifying the mechanism(s) that underlie these interactions; and the lab has been examining proteins related to CFTR with the hopes of identify regions/domains that are common to these proteins and are necessary for these interactions. Lastly, the laboratory is interested in examining how mutations in CFTR affect its ability to function.
Specialized Terms: Cystic fibrosis clinical studies; Cystic fibrosis basic science research (ion transport, Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) function); Cystic fibrosis translational research studies (strategies to bypass the basic defect)
Abnormal trafficking and degradation of TLR4 underlie the elevated inflammatory response in cystic fibrosis
Bruscia E., PX. Zhang, A. Satoh, C. Caputo, R. Medzhitov, A. Shenoy, M.E. Egan D.S. Krause. Abnormal trafficking and degradation of TLR4 underlie the elevated inflammatory response in cystic fibrosis, Journal of Immunology. 186: 6990-6998, 2011. (D.S.K.
Macrophages directly contribute to the hyper pro-inflammatory response in Cftr -/- mice
Bruscia E, Zhang P-X, Ferreira E, Caputo C, Emerson J, Krause D, Egan ME. Macrophages directly contribute to the hyper pro-inflammatory response in Cftr -/- mice. Am J Resp Cell & Mol Biol, 40:295-304, 2009.
Curcumin, a major constituent of the spice tumeric, corrects cystic fibrosis defects
Egan ME, Pearson M, Weiner S, Rubin D, Lukcas G, Du K, Rajendran V, Glockner-Pagel J, Canny S, Caplan MC. Curcumin, a major constituent of the spice tumeric, corrects cystic fibrosis defects. Science, 304:600-2, 2004.
Assessment of CFTR activity in CFTR-null mice after bone marrow transplantation
Bruscia EM, Grove JE, Chang EC, Weiner S, Caputo C, Ferreira EC, Egan ME, Krause DS. Assessment of CFTR activity in CFTR-null mice after bone marrow transplantation, Proc Natl Acad Sci, 103:2965-70, 2006.
Calcium pump inhibitors induce functional expression of DF508-CFTR in cystic fibrosis epithelial cells
Egan ME, Ambrose CA, Cahill PA, Glockner-Pagel J, Balamuth N, Pappoe L, Cho T, Wagner CA, Geibel J, Caplan MC. Calcium pump inhibitors induce functional expression of DF508-CFTR in cystic fibrosis epithelial cells. Nature Med, 8:485-92, 2002.
Rectal potential difference measurements and the functional expression of CFTR in the gastrointestinal epithelia of cystic fibrosis models
Weiner SA, Caputo C, Bruscia E, Ferreira E, Price JE, Krause DS, Egan ME. Rectal potential difference measurements and the functional expression of CFTR in the gastrointestinal epithelia of cystic fibrosis models, Ped Res, 63(1):73-8, 2008.
Full List of PubMed Publications
- Di Pietro C, Zhang PX, O'Rourke TK, Murray TS, Wang L, Britto CJ, Koff JL, Krause DS, Egan ME, Bruscia EM: Ezrin links CFTR to TLR4 signaling to orchestrate anti-bacterial immune response in macrophages. Sci Rep. 2017 Sep 7; 2017 Sep 7. PMID: 28883468
- Egan ME: Effects of Lumacaftor/Ivacaftor in a Pediatric Cohort Homozygous for F508del-CFTR. Am J Respir Crit Care Med. 2017 Apr 1. PMID: 28362199
- Knauf F, Thomson RB, Heneghan JF, Jiang Z, Adebamiro A, Thomson CL, Barone C, Asplin JR, Egan ME, Alper SL, Aronson PS: Loss of Cystic Fibrosis Transmembrane Regulator Impairs Intestinal Oxalate Secretion. J Am Soc Nephrol. 2017 Jan; 2016 Jun 16. PMID: 27313231
- Bruscia EM, Zhang PX, Barone C, Scholte BJ, Homer R, Krause DS, Egan ME: Increased susceptibility of Cftr-/- mice to LPS-induced lung remodeling. Am J Physiol Lung Cell Mol Physiol. 2016 Apr 15; 2016 Feb 5. PMID: 26851259
- Egan ME: Genetics of Cystic Fibrosis: Clinical Implications. Clin Chest Med. 2016 Mar; 2015 Dec 24. PMID: 26857764
- Hegan PS, Kravtsov DV, Caputo C, Egan ME, Ameen NA, Mooseker MS: Restoration of cytoskeletal and membrane tethering defects but not defects in membrane trafficking in the intestinal brush border of mice lacking both myosin Ia and myosin VI. Cytoskeleton (Hoboken). 2015 Sep; 2015 Sep 16. PMID: 26286357
- Vanstone MB, Egan ME, Zhang JH, Carpenter TO: Association between serum 25-hydroxyvitamin D level and pulmonary exacerbations in cystic fibrosis. Pediatr Pulmonol. 2015 May; 2015 Feb 5. PMID: 25657016
- McNeer NA, Anandalingam K, Fields RJ, Caputo C, Kopic S, Gupta A, Quijano E, Polikoff L, Kong Y, Bahal R, Geibel JP, Glazer PM, Saltzman WM, Egan ME: Nanoparticles that deliver triplex-forming peptide nucleic acid molecules correct F508del CFTR in airway epithelium. Nat Commun. 2015 Apr 27; 2015 Apr 27. PMID: 25914116
- Fields RJ, Quijano E, McNeer NA, Caputo C, Bahal R, Anandalingam K, Egan ME, Glazer PM, Saltzman WM: Modified poly(lactic-co-glycolic acid) nanoparticles for enhanced cellular uptake and gene editing in the lung. Adv Healthc Mater. 2015 Feb 18; 2014 Aug 25. PMID: 25156908
- Zhang PX, Cheng J, Zou S, D'Souza AD, Koff JL, Lu J, Lee PJ, Krause DS, Egan ME, Bruscia EM: Pharmacological modulation of the AKT/microRNA-199a-5p/CAV1 pathway ameliorates cystic fibrosis lung hyper-inflammation. Nat Commun. 2015 Feb 10; 2015 Feb 10. PMID: 25665524
- Towle D, Callan DA, Farrel PA, Egan ME, Murray TS: Baby bottle steam sterilizers disinfect home nebulizers inoculated with bacterial respiratory pathogens. J Cyst Fibros. 2013 Sep; 2012 Dec 23. PMID: 23267773
- Zhang PX, Murray TS, Villella VR, Ferrari E, Esposito S, D'Souza A, Raia V, Maiuri L, Krause DS, Egan ME, Bruscia EM: Reduced caveolin-1 promotes hyperinflammation due to abnormal heme oxygenase-1 localization in lipopolysaccharide-challenged macrophages with dysfunctional cystic fibrosis transmembrane conductance regulator. J Immunol. 2013 May 15; 2013 Apr 19. PMID: 23606537
- Fields RJ, Cheng CJ, Quijano E, Weller C, Kristofik N, Duong N, Hoimes C, Egan ME, Saltzman WM: Surface modified poly(β amino ester)-containing nanoparticles for plasmid DNA delivery. J Control Release. 2012 Nov 28; 2012 Oct 5. PMID: 23041278
- Kravtsov DV, Caputo C, Collaco A, Hoekstra N, Egan ME, Mooseker MS, Ameen NA: Myosin Ia is required for CFTR brush border membrane trafficking and ion transport in the mouse small intestine. Traffic. 2012 Aug; 2012 May 8. PMID: 22510086
- Shenoy A, Kopic S, Murek M, Caputo C, Geibel JP, Egan ME: Calcium-modulated chloride pathways contribute to chloride flux in murine cystic fibrosis-affected macrophages. Pediatr Res. 2011 Nov. PMID: 21796019
- Bruscia EM, Zhang PX, Satoh A, Caputo C, Medzhitov R, Shenoy A, Egan ME, Krause DS: Abnormal trafficking and degradation of TLR4 underlie the elevated inflammatory response in cystic fibrosis. J Immunol. 2011 Jun 15; 2011 May 18. PMID: 21593379
- Lu M, Dong K, Egan ME, Giebisch GH, Boulpaep EL, Hebert SC: Mouse cystic fibrosis transmembrane conductance regulator forms cAMP-PKA-regulated apical chloride channels in cortical collecting duct. Proc Natl Acad Sci U S A. 2010 Mar 30; 2010 Mar 15. PMID: 20231442
- Cartiera MS, Ferreira EC, Caputo C, Egan ME, Caplan MJ, Saltzman WM: Partial correction of cystic fibrosis defects with PLGA nanoparticles encapsulating curcumin. Mol Pharm. 2010 Feb 1. PMID: 19886674
- Esquibies AE, Zambrano E, Ziai J, Kesebir D, Touloukian RJ, Egan ME, Reyes-Múgica M, Bazzy-Asaad A: Pulmonary squamous cell carcinoma associated with repaired congenital tracheoesophageal fistula and esophageal atresia. Pediatr Pulmonol. 2010 Feb. PMID: 20054858
- Bruscia EM, Zhang PX, Ferreira E, Caputo C, Emerson JW, Tuck D, Krause DS, Egan ME: Macrophages directly contribute to the exaggerated inflammatory response in cystic fibrosis transmembrane conductance regulator-/- mice. Am J Respir Cell Mol Biol. 2009 Mar; 2008 Sep 5. PMID: 18776130
- Weiner SA, Caputo C, Bruscia E, Ferreira EC, Price JE, Krause DS, Egan ME: Rectal potential difference and the functional expression of CFTR in the gastrointestinal epithelia in cystic fibrosis mouse models. Pediatr Res. 2008 Jan. PMID: 18043508
- Sidani SM, Kirchhoff P, Socrates T, Stelter L, Ferreira E, Caputo C, Roberts KE, Bell RL, Egan ME, Geibel JP: DeltaF508 mutation results in impaired gastric acid secretion. J Biol Chem. 2007 Mar 2; 2006 Dec 18. PMID: 17178714
- Bruscia EM, Ziegler EC, Price JE, Weiner S, Egan ME, Krause DS: Engraftment of donor-derived epithelial cells in multiple organs following bone marrow transplantation into newborn mice. Stem Cells. 2006 Oct; 2006 Jun 22. PMID: 16794262
- Lu M, Leng Q, Egan ME, Caplan MJ, Boulpaep EL, Giebisch GH, Hebert SC: CFTR is required for PKA-regulated ATP sensitivity of Kir1.1 potassium channels in mouse kidney. J Clin Invest. 2006 Mar; 2006 Feb 9. PMID: 16470247
- Bruscia EM, Price JE, Cheng EC, Weiner S, Caputo C, Ferreira EC, Egan ME, Krause DS: Assessment of cystic fibrosis transmembrane conductance regulator (CFTR) activity in CFTR-null mice after bone marrow transplantation. Proc Natl Acad Sci U S A. 2006 Feb 21; 2006 Feb 15. PMID: 16481627
- Egan ME, Pearson M, Weiner SA, Rajendran V, Rubin D, Glöckner-Pagel J, Canny S, Du K, Lukacs GL, Caplan MJ: Curcumin, a major constituent of turmeric, corrects cystic fibrosis defects. Science. 2004 Apr 23. PMID: 15105504
- Egan ME, Glöckner-Pagel J, Ambrose C, Cahill PA, Pappoe L, Balamuth N, Cho E, Canny S, Wagner CA, Geibel J, Caplan MJ: Calcium-pump inhibitors induce functional surface expression of Delta F508-CFTR protein in cystic fibrosis epithelial cells. Nat Med. 2002 May. PMID: 11984593
- Egan ME: CFTR-associated ATP transport and release. Methods Mol Med. 2002. PMID: 11917539