Marie Egan, MD
Research & Publications
Biography
News
Research Summary
Dr Egan has demonstrated a long-term commitment to her overall goal, which is to elucidate the mechanisms that underlie cystic fibrosis (CF) related lung disease, in order to develop innovative and novel therapies and ultimately lengthen the life of patients with this lethal disorder. Dr. Egan’s primary research interest is to understand the function of CFTR in health and disease in epithelial and immune cells.
Extensive Research Description
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, the laboratory is interested in examining how mutations in CFTR affect its ability to function. Lastly, the epithelium interacts with the airway microenvironment and primary immune cells to propagate disease. Dr. Egan has shown that CFTR functions in primary immune cells and this function is altered in CF contributing to disease.
The Egan lab has worked collaboratively to bring forth innovative platforms that could have great impact on CF patients such as gene editing.
Specialized Terms: Cystic fibrosis clinical studies; Cystic fibrosis basic science research (ion transport, Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) function) ion transport; Cystic fibrosis translational research studies (strategies to bypass or correct the basic defect) gene editing, immune response , pediatrics
Coauthors
Research Interests
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; Peptide Nucleic Acids; Nanoparticles; Adaptive Immunity; Translational Medical Research; Airway Management; Gene Editing
Selected Publications
- Global chemical effects of the microbiome include new bile-acid conjugations.Quinn RA, Melnik AV, Vrbanac A, Fu T, Patras KA, Christy MP, Bodai Z, Belda-Ferre P, Tripathi A, Chung LK, Downes M, Welch RD, Quinn M, Humphrey G, Panitchpakdi M, Weldon KC, Aksenov A, da Silva R, Avila-Pacheco J, Clish C, Bae S, Mallick H, Franzosa EA, Lloyd-Price J, Bussell R, Thron T, Nelson AT, Wang M, Leszczynski E, Vargas F, Gauglitz JM, Meehan MJ, Gentry E, Arthur TD, Komor AC, Poulsen O, Boland BS, Chang JT, Sandborn WJ, Lim M, Garg N, Lumeng JC, Xavier RJ, Kazmierczak BI, Jain R, Egan M, Rhee KE, Ferguson D, Raffatellu M, Vlamakis H, Haddad GG, Siegel D, Huttenhower C, Mazmanian SK, Evans RM, Nizet V, Knight R, Dorrestein PC. Global chemical effects of the microbiome include new bile-acid conjugations. Nature 2020, 579: 123-129. PMID: 32103176, PMCID: PMC7252668, DOI: 10.1038/s41586-020-2047-9.
- Single-Cell Transcriptional Archetypes of Airway Inflammation in Cystic Fibrosis.Schupp JC, Khanal S, Gomez JL, Sauler M, Adams TS, Chupp GL, Yan X, Poli S, Zhao Y, Montgomery RR, Rosas IO, Dela Cruz CS, Bruscia EM, Egan ME, Kaminski N, Britto CJ. Single-Cell Transcriptional Archetypes of Airway Inflammation in Cystic Fibrosis. American Journal Of Respiratory And Critical Care Medicine 2020, 202: 1419-1429. PMID: 32603604, PMCID: PMC7667912, DOI: 10.1164/rccm.202004-0991OC.
- Emerging technologies for cystic fibrosis transmembrane conductance regulator restoration in all people with CF.Egan ME. Emerging technologies for cystic fibrosis transmembrane conductance regulator restoration in all people with CF. Pediatric Pulmonology 2021, 56 Suppl 1: S32-S39. PMID: 32681713, PMCID: PMC8114183, DOI: 10.1002/ppul.24965.
- Nanoparticles that deliver triplex-forming peptide nucleic acid molecules correct F508del CFTR in airway epithelium.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. Nature Communications 2015, 6: 6952. PMID: 25914116, PMCID: PMC4480796, DOI: 10.1038/ncomms7952.
- Reduced caveolin-1 promotes hyperinflammation due to abnormal heme oxygenase-1 localization in lipopolysaccharide-challenged macrophages with dysfunctional cystic fibrosis transmembrane conductance regulator.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. Journal Of Immunology (Baltimore, Md. : 1950) 2013, 190: 5196-206. PMID: 23606537, PMCID: PMC3711148, DOI: 10.4049/jimmunol.1201607.
- Surface modified poly(β amino ester)-containing nanoparticles for plasmid DNA delivery.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. Journal Of Controlled Release : Official Journal Of The Controlled Release Society 2012, 164: 41-8. PMID: 23041278, PMCID: PMC3625648, DOI: 10.1016/j.jconrel.2012.09.020.
- Abnormal trafficking and degradation of TLR4 underlie the elevated inflammatory response in cystic fibrosis.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. Journal Of Immunology (Baltimore, Md. : 1950) 2011, 186: 6990-8. PMID: 21593379, PMCID: PMC3111054, DOI: 10.4049/jimmunol.1100396.
- Calcium-modulated chloride pathways contribute to chloride flux in murine cystic fibrosis-affected macrophages.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. Pediatric Research 2011, 70: 447-52. PMID: 21796019, PMCID: PMC3189336, DOI: 10.1203/PDR.0b013e31822f2448.
- Partial correction of cystic fibrosis defects with PLGA nanoparticles encapsulating curcumin.Cartiera MS, Ferreira EC, Caputo C, Egan ME, Caplan MJ, Saltzman WM. Partial correction of cystic fibrosis defects with PLGA nanoparticles encapsulating curcumin. Molecular Pharmaceutics 2010, 7: 86-93. PMID: 19886674, PMCID: PMC2815009, DOI: 10.1021/mp900138a.
- Macrophages directly contribute to the exaggerated inflammatory response in cystic fibrosis transmembrane conductance regulator-/- mice.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. American Journal Of Respiratory Cell And Molecular Biology 2009, 40: 295-304. PMID: 18776130, PMCID: PMC2645527, DOI: 10.1165/rcmb.2008-0170OC.
- Rectal potential difference and the functional expression of CFTR in the gastrointestinal epithelia in cystic fibrosis mouse models.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. Pediatric Research 2008, 63: 73-8. PMID: 18043508, DOI: 10.1203/PDR.0b013e31815b4bc6.
- DeltaF508 mutation results in impaired gastric acid secretion.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. The Journal Of Biological Chemistry 2007, 282: 6068-74. PMID: 17178714, DOI: 10.1074/jbc.M608427200.
- Pseudomonas aeruginosa chronic colonization in cystic fibrosis patients.Murray TS, Egan M, Kazmierczak BI. Pseudomonas aeruginosa chronic colonization in cystic fibrosis patients. Current Opinion In Pediatrics 2007, 19: 83-8. PMID: 17224667, DOI: 10.1097/MOP.0b013e3280123a5d.
- Assessment of cystic fibrosis transmembrane conductance regulator (CFTR) activity in CFTR-null mice after bone marrow transplantation.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. Proceedings Of The National Academy Of Sciences Of The United States Of America 2006, 103: 2965-70. PMID: 16481627, PMCID: PMC1413802, DOI: 10.1073/pnas.0510758103.
- Engraftment of donor-derived epithelial cells in multiple organs following bone marrow transplantation into newborn mice.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 (Dayton, Ohio) 2006, 24: 2299-308. PMID: 16794262, DOI: 10.1634/stemcells.2006-0166.
- Curcumin, a major constituent of turmeric, corrects cystic fibrosis defects.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 (New York, N.Y.) 2004, 304: 600-2. PMID: 15105504, DOI: 10.1126/science.1093941.
- Calcium-pump inhibitors induce functional surface expression of Delta F508-CFTR protein in cystic fibrosis epithelial cells.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. Nature Medicine 2002, 8: 485-92. PMID: 11984593, DOI: 10.1038/nm0502-485.
- Cystic fibrosis transmembrane conductance receptor modulator therapy in cystic fibrosis, an update.Egan ME. Cystic fibrosis transmembrane conductance receptor modulator therapy in cystic fibrosis, an update. Current Opinion In Pediatrics 2020, 32: 384-388. PMID: 32374578, DOI: 10.1097/MOP.0000000000000892.
- Effects of Lumacaftor/Ivacaftor in a Pediatric Cohort Homozygous for F508del-CFTR.Egan ME. Effects of Lumacaftor/Ivacaftor in a Pediatric Cohort Homozygous for F508del-CFTR. American Journal Of Respiratory And Critical Care Medicine 2017, 195: 849-850. PMID: 28362199, DOI: 10.1164/rccm.201611-2290ED.
- Increased susceptibility of Cftr-/- mice to LPS-induced lung remodeling.Bruscia E, Zhang PX, Barone C, Scholte B, Homer RJ, Krause D, Egan ME. Increased susceptibility of Cftr-/- mice to LPS-induced lung remodeling. American Journal Of Physiology. Lung Cellular And Molecular Physiology 2016, 310: L711-9. PMID: 26851259, PMCID: PMC4836110, DOI: 10.1152/ajplung.00284.2015.
- Ezrin links CFTR to TLR4 signaling to orchestrate anti-bacterial immune response in macrophages.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. Scientific Reports 2017, 7: 10882. PMID: 28883468, PMCID: PMC5589856, DOI: 10.1038/s41598-017-11012-7.
- Genetics of Cystic Fibrosis: Clinical Implications.Egan ME. Genetics of Cystic Fibrosis: Clinical Implications. Clinics In Chest Medicine 2016, 37: 9-16. PMID: 26857764, DOI: 10.1016/j.ccm.2015.11.002.
- Modified poly(lactic-co-glycolic acid) nanoparticles for enhanced cellular uptake and gene editing in the lung.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. Advanced Healthcare Materials 2015, 4: 361-6. PMID: 25156908, PMCID: PMC4339402, DOI: 10.1002/adhm.201400355.
- Pharmacological modulation of the AKT/microRNA-199a-5p/CAV1 pathway ameliorates cystic fibrosis lung hyper-inflammation.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. Nature Communications 2015, 6: 6221. PMID: 25665524, PMCID: PMC4324503, DOI: 10.1038/ncomms7221.
- Baby bottle steam sterilizers disinfect home nebulizers inoculated with bacterial respiratory pathogens.Towle D, Callan DA, Farrel PA, Egan ME, Murray TS. Baby bottle steam sterilizers disinfect home nebulizers inoculated with bacterial respiratory pathogens. Journal Of Cystic Fibrosis : Official Journal Of The European Cystic Fibrosis Society 2013, 12: 512-6. PMID: 23267773, DOI: 10.1016/j.jcf.2012.11.013.
- Association between serum 25-hydroxyvitamin D level and pulmonary exacerbations in cystic fibrosis.Vanstone MB, Egan ME, Zhang JH, Carpenter TO. Association between serum 25-hydroxyvitamin D level and pulmonary exacerbations in cystic fibrosis. Pediatric Pulmonology 2015, 50: 441-6. PMID: 25657016, DOI: 10.1002/ppul.23161.
- Nanoparticles for delivery of agents to fetal lungs.Ullrich SJ, Freedman-Weiss M, Ahle S, Mandl HK, Piotrowski-Daspit AS, Roberts K, Yung N, Maassel N, Bauer-Pisani T, Ricciardi AS, Egan ME, Glazer PM, Saltzman WM, Stitelman DH. Nanoparticles for delivery of agents to fetal lungs. Acta Biomaterialia 2021, 123: 346-353. PMID: 33484911, PMCID: PMC7962939, DOI: 10.1016/j.actbio.2021.01.024.
- SPLUNC1: a novel marker of cystic fibrosis exacerbations.Khanal S, Webster M, Niu N, Zielonka J, Nunez M, Chupp G, Slade MD, Cohn L, Sauler M, Gomez JL, Tarran R, Sharma L, Dela Cruz CS, Egan M, Laguna T, Britto CJ. SPLUNC1: a novel marker of cystic fibrosis exacerbations. The European Respiratory Journal 2021, 58 PMID: 33958427, PMCID: PMC8571118, DOI: 10.1183/13993003.00507-2020.
- Understanding the Host in the Management of Pneumonia. An Official American Thoracic Society Workshop Report.Dela Cruz CS, Evans SE, Restrepo MI, Dean N, Torres A, Amara-Elori I, Awasthi S, Caler E, Cao B, Chalmers JD, Chastre J, Cohen TS, Cohen AH, Crothers K, Di YP, Egan ME, Feldman C, Gautam S, Halstead ES, Herold S, Jones BE, Luna C, Niederman MS, Mendez R, Menendez R, Mizgerd JP, Nusrat R, Ramirez J, Shindo Y, Waterer G, Yeligar SM, Wunderink RG. Understanding the Host in the Management of Pneumonia. An Official American Thoracic Society Workshop Report. Annals Of The American Thoracic Society 2021, 18: 1087-1097. PMID: 34242148, PMCID: PMC8328365, DOI: 10.1513/AnnalsATS.202102-209ST.
- Surface conjugation of antibodies improves nanoparticle uptake in bronchial epithelial cells.Luks VL, Mandl H, DiRito J, Barone C, Freedman-Weiss MR, Ricciardi AS, Tietjen GG, Egan ME, Saltzman WM, Stitelman DH. Surface conjugation of antibodies improves nanoparticle uptake in bronchial epithelial cells. PloS One 2022, 17: e0266218. PMID: 35385514, PMCID: PMC8986008, DOI: 10.1371/journal.pone.0266218.
Clinical Trials
Conditions | Study Title |
---|---|
Diseases of the Endocrine System; Genetics - Adult; Genetics - Pediatric | VX-121 Combination Therapy in Subjects With Cystic Fibrosis VX20-121-103 |
Hepatitis; HIV/AIDS; Immune System; Infectious Diseases | Screening In Anticipation of Future Research |