John Engelhardt, PhD
Professor of Anatomy and Cell Biology
Introduction
Research in the Engelhardt laboratory focuses on the molecular basis of cystic fibrosis disease pathologies, and on the development of gene therapies for this disorder. Included are four major research areas include the study of: 1) lung molecular and cellular biology as it relates to the pathogenesis and treatment of cystic fibrosis (CF) lung disease, 2) the development of viral vector for gene therapy and gene editing, 3) pathogenesis cystic fibrosis related diabetes, and 4) the study of airway stem cell niches, the regulatory mechanisms that control stem cell proliferation and repair in the airway, and the development of cell-based therapies for CF using stem cells.
Current Positions
- Professor of Anatomy and Cell Biology
- Professor of Internal Medicine
- Director, Center for Gene Therapy
- Roy J. Carver Chair in Molecular Medicine
Education
- BS in Biochemistry, Iowa State University, Ames, Iowa, United States
- PhD in Human Genetics, Johns Hopkins University, Baltimore, Maryland, United States
- Research Associate in HHMI, University of Michigan, Ann Arbor, Michigan, United States
- Research Associate in Internal Medicine, University of Michigan, Ann Arbor, Michigan, United States
Graduate Program Affiliations
Center, Program and Institute Affiliations
Research Interests
- Molecular basis of cystic fibrosis disease, pathologies, and the development of gene therapies for this disorder.
Selected Publications
- In utero and postnatal ivacaftor/lumacaftor therapy rescues multiorgan disease in CFTR-F508del ferrets.Evans IA, Sun X, Liang B, Vegter AR, Guo L, Lynch TJ, Zhang Y, Zhang Y, Yi Y, Yang Y, Feng Z, Park SY, Shonka A, McCumber H, Qi L, Wu P, Liu G, Lacina A, Wang K, Gibson-Corley KN, Meyerholz DK, Limoli DH, Rosen BH, Yan Z, Bartels DJ, Engelhardt JF.JCI Insight. 2024 Apr 22;9(8):e157229. doi: 10.1172/jci.insight.157229.PMID: 38646935
- Durable transgene expression and efficient re-administration after rAAV2.5T-mediated fCFTRΔR gene delivery to adult ferret lungs.Tang Y, Ebadi M, Lei J, Feng Z, Fakhari S, Wu P, Smith MD, Limberis MP, Kolbeck R, Excoffon KJ, Yan Z, Engelhardt JF.Mol Ther Methods Clin Dev. 2024 Mar 28;32(2):101244. doi: 10.1016/j.omtm.2024.101244. eCollection 2024 Jun 13.PMID: 38638546 Free PMC article.
- Inhibition of DNA-dependent protein kinase catalytic subunit boosts rAAV transduction of polarized human airway epithelium.Ning K, Zhang X, Feng Z, Hao S, Kuz CA, Cheng F, Park SY, McFarlin S, Engelhardt JF, Yan Z, Qiu J.Mol Ther Methods Clin Dev. 2023 Sep 21;31:101115. doi: 10.1016/j.omtm.2023.101115. eCollection 2023 Dec 14.PMID: 37841417 Free PMC article.
- Transgenic ferret models define pulmonary ionocyte diversity and function.Yuan F, Gasser GN, Lemire E, Montoro DT, Jagadeesh K, Zhang Y, Duan Y, Ievlev V, Wells KL, Rotti PG, Shahin W, Winter M, Rosen BH, Evans I, Cai Q, Yu M, Walsh SA, Acevedo MR, Pandya DN, Akurathi V, Dick DW, Wadas TJ, Joo NS, Wine JJ, Birket S, Fernandez CM, Leung HM, Tearney GJ, Verkman AS, Haggie PM, Scott K, Bartels D, Meyerholz DK, Rowe SM, Liu X, Yan Z, Haber AL, Sun X, Engelhardt JF.Nature. 2023 Sep;621(7980):857-867. doi: 10.1038/s41586-023-06549-9. Epub 2023 Sep 20.PMID: 37730992 Free PMC article.
- Understanding and addressing the needs of people with cystic fibrosis in the era of CFTR modulator therapy.Hisert KB, Birket SE, Clancy JP, Downey DG, Engelhardt JF, Fajac I, Gray RD, Lachowicz-Scroggins ME, Mayer-Hamblett N, Thibodeau P, Tuggle KL, Wainwright CE, De Boeck K.Lancet Respir Med. 2023 Oct;11(10):916-931. doi: 10.1016/S2213-2600(23)00324-7. Epub 2023 Sep 9.PMID: 37699420 Review.
- Inflammatory Activity of Epithelial Stem Cell Variants from Cystic Fibrosis Lungs Is Not Resolved by CFTR Modulators.Wang S, Niroula S, Hoffman A, Khorrami M, Khorrami M, Yuan F, Gasser GN, Choi S, Liu B, Li J, Metersky ML, Vincent M, Crum CP, Boucher RC, Karmouty-Quintana H, Huang HJ, Sheshadri A, Dickey BF, Parekh KR, Engelhardt JF, McKeon FD, Xian W.Am J Respir Crit Care Med. 2023 Nov 1;208(9):930-943. doi: 10.1164/rccm.202305-0818OC.PMID: 37695863 Free PMC article.
- Orthotopic Ferret Tracheal Transplantation Using a Recellularized Bioengineered Graft Produces Functional Epithelia.Pai AC, Swatek AM, Lynch TJ, Ahlers BA, Ievlev V, Engelhardt JF, Parekh KR.Bioengineering (Basel). 2023 Jun 29;10(7):777. doi: 10.3390/bioengineering10070777.PMID: 37508804 Free PMC article.
- Immunohistochemical detection of MUC5AC and MUC5B mucins in ferrets.Meyerholz DK, Leidinger MR, Adam Goeken J, Businga TR, Vizuett S, Akers A, Evans I, Zhang Y, Engelhardt JF.BMC Res Notes. 2023 Jun 22;16(1):111. doi: 10.1186/s13104-023-06388-x.PMID: 37349833 Free PMC article.
- Genome Editing in Ferret Airway Epithelia Mediated by CRISPR/Nucleases Delivered with Amphiphilic Shuttle Peptides.Luo M, Ma J, Cheng X, Wu S, Bartels DJ, Guay D, Engelhardt JF, Liu X.Hum Gene Ther. 2023 Aug;34(15-16):705-718. doi: 10.1089/hum.2023.016. Epub 2023 Jul 20.PMID: 37335046 Free PMC article.
- Sonic Hedgehog Signaling Is Essential for Pulmonary Ionocyte Specification in Human and Ferret Airway Epithelia.Cai Q, Luo M, Tang Y, Yu M, Yuan F, Gasser GN, Liu X, Engelhardt JF.Am J Respir Cell Mol Biol. 2023 Sep;69(3):295-309. doi: 10.1165/rcmb.2022-0280OC.PMID: 37141531 Free PMC article.