大象传媒

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Martina Gentzsch, PhD

Associate Professor

Specialty Areas:

Ion channel function in bronchial, nasal, and intestinal epithelia.
Personalized CFTR-targeting therapeutics for cystic fibrosis.
Cell biology and ion channel function of SARS-CoV-2 envelope protein.
Preclinical assays for evaluation of drugs that target CFTR, ENaC, CaCC, and SARS-CoV-2 envelope protein.

Chronology:

1997
Ph.D. (summa cum laude) Cell Biology: Protein Processing, University of Regensburg, Germany
1997-1998
Postdoctoral Fellow, Laboratory of Dr. W. Tanner, Institute of Cell Biology, University of Regensburg, Germany
1998-2001
Postdoctoral Research Fellow, Laboratory of Dr. J.R. Riordan, Mayo Clinic, Scottsdale, AZ
2001-2005
Research Associate, Mayo Clinic College of Medicine, Scottsdale, AZ
2005-2012
Assistant Professor of Cell and Developmental Biology, 大象传媒, Chapel Hill, NC
2012-2015
Director, Correction Core (NIH MTCC), Cystic Fibrosis/Pulmonary Research & Treatment Center, 大象传媒
2012-2016
Assistant Professor of Cell Biology and Physiology, 大象传媒
2015-Present
Director, CFTR Functional Analysis Core (CFF RDP), Marsico Lung Institute (MLI), 大象传媒
2015-Present
Director, Cystic Fibrosis Molecular/Functional Measurement Pre-Clinical Core (NIH CFRTCC) MLI, 大象传媒
2016-2020
Associate Professor of Cell Biology and Physiology, 大象传媒
2020-Present
Associate Professor of Pediatrics, Pediatric Pulmonology, 大象传媒
2020-Present
Adjunct Associate Professor of Cell Biology and Physiology, 大象传媒

Research Focus:

A major goal of my studies聽is to uncover potential targets for therapy of chronic lung diseases, including cystic fibrosis (CF).

Specifically, I work on pharma颅cological modulation of airway epithelial ion channels, such as the CF transmembrane conductance regulator (CFTR) that is mutated in CF, the epithelial sodium channel (ENaC), and calcium-activated chloride channels (CaCCs) in physiologically relevant model systems. In particular, my research focuses on CFTR processing, intracellular trafficking, and rescue. My laboratory is interested in improving pre-clinical models for CFTR research and drug discovery in CF, and we have developed reliable methodology to analyze ion channel physiology in relevant primary human bronchial epithelial (HBE), human nasal epithelial (HNE) and GI cultures. We are applying these techniques and electrophysiological assays to evaluate CFTR rescue by small-molecule compounds in primary and conditionally reprogrammed epithelial nasal, bronchial, and intestinal cultures and tissues. In addition, we have developed and are utilizing state-of-the-art pre-clinical assays to investigate the efficacy of novel therapeutic approaches to CF in relevant in vitro, ex vivo, and in vivo models of CF including organoids from different tissues.

More recently, my research has been investigating how bacterial and viral infection and inflammation affect ion channel function and protein interactions in airway epithelia. Furthermore, we are developing novel precision medicine models for lung diseases beyond CF. Recently, we have utilized our ion channel expertise to investigate properties of the SARS-CoV-2 envelope viroporin. This viral ion channel plays a crucial role in SARS-CoV-2 pathogenesis and is being assessed as a target for development of COVID-19 therapeutics.

Cartoon and immunofluorescent confocal images depicting the rescue of CFTR. A more detailed description is in the figure caption.
Rescue of CFTR. The mutant CFTR protein, F508del, is retained at the ER in differentiated primary human bronchial epithelial (HBE) cells. Corrector compounds promote transfer of mutant CFTR from the ER to the apical membrane, whereas potentiator compounds increase activity of CFTR at the apical surface. The insets show confocal immunofluorescence of CFTR (green) expressed in primary HBE cells. F508del CFTR is retained within the cell (bottom panel) while wild-type CFTR is at the cell surface (top panel). Cilia are stained in red and nuclei in blue.
A graph depicting correction of mutant CFTR in CF HBE cells. A more detailed description is in the figure caption.
Correction of mutant CFTR in CF HBE cells (P67L/鈭咶508). Short-circuit currents were measured in Ussing chambers. Amiloride was added to inhibit ENaC, forskolin to stimulate CFTR, VX-770 to potentiate CFTR, and CFTR inhibitor-172 to inhibit CFTR. The blue stripe, treatment with VX-809 (5 碌M) + VX-770 (1 碌M), resulted in the highest level of CFTR function for this particular mutant.
Fluorescent western blot image demonstrating that CFTR impedes proteolysis of ENaC. A more detailed description is in the figure caption.
CFTR impedes proteolysis of ENaC. Expression of increasing amounts of CFTR (shown in red) diminishes appearance of matriptase-induced proteolytic fragments of 伪-ENaC (shown in green). CFTR, ENaC, and matriptase were co-expressed in Xenopus oocytes. Molecular weight markers (250, 150, 100, 75 and 50 kDa) are shown in yellow.
Microscopy image depicting virally delivered expression of CFTR in epithelial cells. More detailed information is in the figure caption.
Virally delivered expression of CFTR in epithelial cells. Wild-type CFTR resides at the apical membrane in primary HBE cells. Cilia are stained in blue, virally delivered CFTR-expressing cells in green, and CFTR is shown in red.
Microscopy image of human primary nasal cells grown as 3D sphere cultures. A more detailed description is in the figure caption.
Human primary nasal cells grown as 3D sphere cultures. Nasal epithelial cells obtained from individuals can be cultured into 3D spheres and used for studying ion channel function. Apical membrane and cilia are stained in red, cells in green, and nuclei in blue.
Microscopy image of a human bronchial sphere grown in matrigel. A more detailed description is in the figure caption.
Human primary bronchial sphere grown in matrigel. Bronchial cells obtained from individuals can be cultured into 3D spheres for studying ion channel function. When grown in matrigel, the apical surface faces the inside of the sphere. This section is stained with AB PAS. Bar=50碌m.

Selected Bibliography:

  1. Gentzsch M, Esther CR Jr, Ribeiro CMP. . Lancet Respir Med. 2024 Nov;12(11):e67. doi: 10.1016/S2213-2600(24)00305-9. PMID: 39395437.
  2. Okuda K, Gentzsch M. Am J Respir Crit Care Med.2024 Sep 15;210(6):705-707. doi: 10.1164/rccm.202404-0727ED. PMID: 38701428. PMCID: PMC11418888.
  3. Gentzsch M, Baker B, Cholon DM, Kam CW, McKinzie CJ, Despotes KA, Boyles SE, Quinney NL, Esther CR Jr, Ribeiro CMP. . ERJ Open Res. 2024 Jan 15;10(1):00746-2023. doi: 10.1183/23120541.00746-2023. PMID: 38226069; PMCID: PMC10789252.
  4. Cholon DM, Greenwald MA, Higgs MG, Quinney NL, Boyles SE, Meinig SL, Minges JT, Chaubal A, Tarran R, Ribeiro CMP, Wolfgang MC, Gentzsch M. . Cells. 2023 Nov 13;12(22):2618. doi: 10.3390/cells12222618. PMID: 37998353; PMCID: PMC10670530.
  5. Mikami Y, Grubb BR, Rogers TD, Dang H, Asakura T, Kota P, Gilmore RC, Okuda K, Morton LC, Sun L, Chen G, Wykoff JA, Ehre C, Vilar J, van Heusden C, Livraghi-Butrico A, Gentzsch M, Button B, Stutts MJ, Randell SH, O’Neal WK, Boucher RC. . Sci Transl Med. 2023 Jun 7;15(699):eabo7728. doi: 10.1126/scitranslmed.abo7728. PMID: 37285404. PMCID: PMC10664029.
  6. Ramalho AS, Amato F, Gentzsch M. . J Cyst Fibros. 2023 Mar;22 Suppl 1(Suppl 1):S32-S38. doi: 10.1016/j.jcf.2022.11.007. PMID: 36529661. PMCID: PMC9992303.
  7. Ribeiro CMP,聽Gentzsch M.听. Curr Opin Pharmacol.听2022 Dec;67:102289. doi: 10.1016/j.coph.2022.102289. PMID: 36152600.
  8. Ruan J, Liang D, Yan W, Zhong Y, Talley DC, Rai G, Tao D, LeClair CA, Simeonov A, Zhang Y, Chen F, Quinney NL, Boyles SE, Cholon DM,聽Gentzsch M, Henderson MJ, Xue F, Fang S.听. Mol Biol Cell. 2022 Nov 1;33(13):ar120. doi: 10.1091/mbc.E22-06-0233. PMID: 36074076. PMCID: PMC9634977.
  9. Lee RE, Lewis CA, He L, Bulik-Sullivan EC, Gallant SC, Mascenik TM, Dang H, Cholon DM, Gentzsch M, Morton LC, Minges JT, Theile JW, Castle NA, Knowles MR, Kimple AJ, Randell SH. . J Clin Invest. 2022 Sep 15;132(18):e154571. doi: 10.1172/JCI154571. PMID: 35900863; PMCID: PMC9479597.
  10. Harrison NL, Abbott GW, Gentzsch M, Aleksandrov A, Moroni A, Thiel G, Grant S, Nichols CG, Lester HA, Hartel A, Shepard K, Garcia DC, Yazawa M. Commun Biol. 2022 Aug 25;5(1):859. doi: 10.1038/s42003-022-03669-2. PMID: 36008538; PMCID: PMC9411608.
  11. Cholon DM, Gentzsch M. . Curr Opin Pharmacol. 2022 Jun;64:102210. doi: 10.1016/j.coph.2022.102210. PMID: 35462105. PMCID: PMC9167699.
  12. Ghigo A, Murabito A, Sala V, Pisano AR, Bertolini S, Gianotti A, Caci E, Montresor A, Premchandar A, Pirozzi F, Ren K, Della Sala A, Mergiotti M, Richter W, de Poel E, Matthey M, Caldrer S, Cardone RA, Civiletti F, Costamagna A, Quinney NL, Butnarasu C, Visentin S, Ruggiero MR, Baroni S, Crich SG, Ramel D, Laffargue M, Tocchetti CG, Levi R, Conti M, Lu XY, Melotti P, Sorio C, De Rose V, Facchinetti F, Fanelli V, Wenzel D, Fleischmann BK, Mall MA, Beekman J, Laudanna C, Gentzsch M, Lukacs GL, Pedemonte N, Hirsch E. . Sci Transl Med. 2022 Mar 30;14(638):eabl6328. doi: 10.1126/scitranslmed.abl6328. PMID: 35353541. PMCID: PMC9869178.
  13. Morrison CB, Shaffer KM, Araba KC, Markovetz MR, Wykoff JA, Quinney NL, Hao S, Delion MF, Flen AL, Morton LC, Liao J, Hill DB, Drumm ML, O’Neal WK, Kesimer M,聽Gentzsch M, Ehre C.听. Eur Respir J. 2022 Feb 3;59(2):2100185. doi: 10.1183/13993003.00185-2021. PMID: 34172469. PMCID: PMC8859811.
  14. Farinha CM, Gentzsch M. . Int J Mol Sci. 2021 Dec 7;22(24):13196. doi: 10.3390/ijms222413196. PMID: 34947992; PMCID: PMC8703571.
  15. Ribeiro CMP, Gentzsch M. . Cells. 2021 Nov 22;10(11):3260. doi: 10.3390/cells10113260. PMID: 34831482; PMCID: PMC8619863.
  16. Dang Y, van Heusden C, Nickerson V, Chung F, Wang Y, Quinney NL, Gentzsch M, Randell SH, Moulton HM, Kole R, Ni A, Juliano RL, Kreda SM. . Nucleic Acids Res. 2021 Jun 21;49(11):6100-6113. doi: 10.1093/nar/gkab488. PMID: 34107015; PMCID: PMC8216463.
  17. Okuda K, Dang H, Kobayashi Y, Carraro G, Nakano S, Chen G, Kato T, Asakura T, Gilmore RC, Morton LC, Lee RE, Mascenik T, Yin WN, Barbosa Cardenas SM, O鈥橬eal YK, Minnick CE, Chua M, Quinney NL, Gentzsch M, Anderson CW, Ghio A, Matsui H, Nagase T, Ostrowski LE, Grubb BR, Olsen JC, Randell SH, Stripp BR, Tata PR, O鈥橬eal WK, Boucher RC. . Am J Respir Crit Care Med. 2021 May 15;203(10):1275-1289. PMID: 33321047. PMCID: PMC8456462.
  18. He L, Kennedy AS, Houck S, Aleksandrov A, Quinney NL, Cyr-Scully A, Cholon DM,聽Gentzsch M, Randell SH, Ren HY, Cyr DM.听. Mol Biol Cell. 2021 Apr 1;32(7):538-553. PMID: 33534640; PMCID: PMC8101465.
  19. Gentzsch M, Cholon DM, Quinney NL, Martino MEB, Minges JT, Boyles SE, Guhr Lee TN, Esther CR Jr, Ribeiro CMP. . Front Pharmacol. 2021 Mar 30;12:628722. PMID: 33859562; PMCID: PMC8042279.
  20. Xu J, Livraghi-Butrico A, Hou X, Rajagopalan C, Zhang J, Song J, Jiang H, Wei HG, Wang H, Bouhamdan M, Ruan J, Yang D, Qiu Y, Youming X, Barrett RP, McClellan SA, Mou H, Wu Q, Chen X, Rogers TD, Wilkinson KJ, Gilmore RC, Esther CR Jr, Zaman K, Liang X, Sobolic M, Hazlett L, Zhang K, Frizzell RA, Gentzsch M, O’Neal WK, Grubb BR, Chen YE, Boucher RC, Sun F. . JCI Insight. 2021 Jan 11;6(1):e139813. PMID: 33232302; PMCID:聽PMC7821608.
  21. Gentzsch M, Rossier BC. . Function (Oxf). 2020;1(2):zqaa024. PMID: 33201937;聽PMCID: PMC7662147.
  22. Guhr Lee TN, Cholon DM, Quinney NL, Gentzsch M, Esther CR Jr. . J Cyst Fibros. 2020 Sep;19(5):746-751. PMID: 32536510;聽PMCID: PMC7492410.
  23. McCravy MS, Quinney NL, Cholon DM, Boyles SE, Jensen TJ, Aleksandrov AA, Donaldson SH, Noone PG, Gentzsch M.听. Eur Respir J. 2020 Jul 30;56(1):2000062. PMID: 32265312; PMCID:聽PMC7406131.
  24. Armirotti A, Tomati V, Matthes E, Veit G, Cholon DM, Phuan PW, Braccia C, Guidone D, Gentzsch M, Lukacs GL, Verkman AS, Galietta LJV, Hanrahan JW, Pedemonte N. . Sci Rep. 2019 Jul 16;9(1):10310. PMID: 31311979;聽PMCID: PMC6635361.
  25. Clancy JP, Cotton CU, Donaldson SH, Solomon GM, VanDevanter DR, Boyle MP, Gentzsch M, Nick JA, Illek B, Wallenburg JC, Sorscher EJ, Amaral MD, Beekman JM, Naren AP, Bridges RJ, Thomas PJ, Cutting G, Rowe S, Durmowicz AG, Mense M, Boeck KD, Skach W, Penland C, Joseloff E, Bihler H, Mahoney J, Borowitz D, Tuggle KL. . J Cyst Fibros. 2019 Jan;18(1):22-34. PMID: 29934203; PMCID:聽PMC6301143.
  26. Gentzsch M, Cholon DM, Quinney NL, Boyles SE, Martino MEB, 聽Ribeiro CMP. . Eur Respir J. 2018 Dec 20;52(6):1801133. PMID: 30287473;聽PMCID: PMC6482470.
  27. Moorefield EC, Blue RE, Quinney NL, Gentzsch M, Ding S. . BMC Cell Biol. 2018 Aug 15;19(1):15. PMID: 30111276;聽PMCID: PMC6094565.
  28. Kota P, Gentzsch M, Dang Y, Boucher R, Stutts M. . J Gen Physiol. 2018 Aug 6;150(8):1179-1187. PMID: 29980634;聽PMCID: PMC6080898.
  29. Gentzsch M, Mall MA. . Chest. 2018 Aug;154(2):383-393. PMID: 29750923; PMCID: PMC6113631. Review.
  30. Cholon DM, Gentzsch M. . J Cyst Fibros. 2018 Mar;17(2S):S52-S60. PMID: 28986017;聽PMCID: PMC5828944.
  31. Tomati V, Caci E, Ferrera L, Pesce E, Sondo E, Cholon DM, Quinney NL, Boyles SE, Armirotti A, Ravazzolo R, Galietta LJ, Gentzsch M, Pedemonte N. . JCI Insight. 2018 Feb 8;3(3):e98699. PMID: 29415893;聽PMCID: PMC5821210.
  32. Guimbellot JS, Leach JM, Chaudhry IG, Quinney NL, Boyles SE, Chua M, Aban I, Jaspers I, Gentzsch M.听. JCI Insight. 2017 Nov 16;2(22):e95734. PMID: 29202459;聽PMCID: PMC5752372.
  33. Gentzsch M, Boyles SE, Cheluvaraju C, Chaudhry IG, Quinney NL, Cho C, Dang H, Liu X, Schlegel R, Randell SH. . Am J Respir Cell Mol Biol. 2017 May;56(5):568-574. PMID: 27983869;聽PMCID: PMC5449492.
  34. Gentzsch M, Ren HY, Houck SA, Quinney NL, Cholon DM, Sopha P, Chaudhry IG, Das J, Dokholyan NV, Randell SH, Cyr DM. . Am J Physiol Lung Cell Mol Physiol. 2016 Sep 1;311(3):L550-9. PMID: 27402691;聽PMCID: PMC5142211.
  35. Watson MJ, Lee SL, Marklew AJ, Gilmore RC, Gentzsch M, Sassano MF, Gray MA, Tarran R. . Sci Rep. 2016 Jun 9;6:27390. PMID: 27278076;聽PMCID: PMC4899698.
  36. Cholon DM, Esther CR Jr, Gentzsch M.听. Expert Rev Precis Med Drug Dev. 2016;1(3):235-243. PMID: 27482545;聽PMCID: PMC4963025.
  37. Kota P, Buchner G, Chakraborty H, Dang YL, He H, Garcia GJM, Kubelka J, Gentzsch M, Stutts MJ, Dokholyan NV. . J Biol Chem. 2014 Aug 15;289(33):23029-23042. PMID: 24973914;聽PMCID: PMC4132802.
  38. Cholon DM, Quinney NL, Fulcher ML, Esther CR, Das J, Dokholyan NV, Randell SH, Boucher RC,聽Gentzsch M.听. Sci Transl Med. 2014 Jul 23;6(246):246ra96. PMID: 25101886;聽PMCID: PMC4272825.
  39. Aleksandrov AA, Kota P, Cui L, Jensen T, Alekseev AE, Reyes S, He L, Gentzsch M, Aleksandrov LA, Dokholyan NV, Riordan JR. . J Mol Biol. 2012 May 25;419(1-2):41-60. PMID: 22406676;聽PMCID: PMC3891843.
  40. Kota P, Garc铆a-Caballero A, Dang H, Gentzsch M, Stutts MJ, Dokholyan NV. . Biochemistry. 2012 Apr 24;51(16):3460-9. PMID: 22471557;聽PMCID: PMC3404201.
  41. Clunes LA, Davies CM, Coakley RD, Aleksandrov AA, Henderson AG, Zeman KL, Worthington EN, Gentzsch M, Kreda SM, Cholon D, Bennett WD, Riordan JR, Boucher RC, Tarran R. . FASEB J. 2012 Feb;26(2):533-45. PMID: 21990373;聽PMCID: PMC3290447.
  42. Kreda SM, Gentzsch M.听. Methods Mol Biol. 2011;742:15-33. PMID: 21547724.
  43. Johnson JS, Gentzsch M, Zhang L, Ribeiro CM, Kantor B, Kafri T, Pickles RJ, Samulski RJ. . PLoS Pathog. 2011 May;7(5):e1002053. PMID: 21625534;聽PMCID: PMC3098238.
  44. Hegedus T, Gentzsch M, Riordan JR. . In: The ABC transporters of human physiology and disease. Chapter 10. Linton K, Holland B (eds). World Scientific Publishing, 2011. pp. 269-309.
  45. Gentzsch M, Dang H, Dang Y, Garcia-Caballero A, Suchindran H, Boucher RC, Stutts MJ.听. J Biol Chem.聽2010 Oct 15;285(42):32227-32.听 PMID: 20709758;聽PMCID: PMC2952223.听鈥淧aper of the Week鈥�
  46. Aleksandrov AA, Kota P, Aleksandrov L, He L, Jensen T, Cui L,聽Gentzsch M, Dokholyan NV, Riordan JR.听. J Mol Biol.聽2010 Aug 13;401(2):194-210.听PMID: 20561529;聽PMCID: PMC4361937.
  47. Cholon DM, O’Neal WK, Randell SH, Riordan JR, Gentzsch M.听. Am J Physiol Lung Cell Mol Physiol. 2010 Mar;298(3):L304-14. PMID: 20008117;聽PMCID: PMC2838667.
  48. Hutt DM, Herman, DM, Rodrigues, APC, Noel S, Pilewski JM, Matteson J, Hoch B, Kellner W, Kelly JW, Richarson J, Thomas PJ, Matsumura Y, Skach WR,聽Gentzsch M, Riordan JR, Sorscher EJ, Okiyonad T, Lukacs GL, Frizzell RA, Manning G, Gottesfeld JM, Balch WE.听. Nat Chem Biol. 2010 Jan;6(1):25-33. PMID: 19966789;聽PMCID: PMC2901172.
  49. Young A, Gentzsch M, Jia Y, Abban CY, Meneses PI, Bridges RJ, Bradbury NA. . Biochem J. 2009 Jul 15;421(3):377-85. PMID: 19442237.
  50. Fulcher ML, Gabriel SE, Olsen JC, Tatreau JR, Gentzsch M, Livanos E, Saavedra MT, Salmon P, Randell SH. . Am J Physiol Lung Cell Mol Physiol. 2009 Jan;296(1):L82-91. PMID: 18978040;聽PMCID: PMC2636952.
  51. Chang XB, Mengos A, Hou YX, Cui L, Jensen TJ, Aleskandrov A, Riordan JR, Gentzsch M. . J Cell Sci. 2008 Sep 1;121(Pt 17):2814-23. PMID: 18682497;聽PMCID: PMC2677381.
  52. Gentzsch M, Choudhury A, Chang X-B, Pagano R, Riordan JR. . J Cell Sci. 2007 Feb 1;120(Pt 3):447-55. PMID: 17213331.
  53. Thelin, WR, Chen, Y, Gentzsch M, Kreda S, Sallee J, Scarlett C, Borchers C, Jacobson, K, Stutts KJ, Milgram S. . J Clin Invest. 2007 Feb;117(2):364-74. PMID: 17235394;聽PMCID: PMC1765518.
  54. Cui L, Aleksandrov L, Chang X-B, Hou YX, He L, Hegedus T, Gentzsch M, Aleksandrov A, Balch WE, Riordan JR. . J Mol Biol. 2007 Jan 26;365(4):981-94. PMID: 17113596.
  55. Hegedus T, Aleksandrov A, Cui L,聽Gentzsch M, Chang X-B, Riordan JR.听. Biochim Biophys Acta. 2006 May;1758(5):565-72. PMID: 16624253.
  56. Grubb BR, Gabriel SE, Mengos A, Gentzsch M, Randell SH, Van Heeckeren AM, Knowles MR, Drumm ML, Riordan JR, Boucher RC. . Am J Respir Cell Mol Biol. 2006 Mar;34(3):355-63. PMID: 16284361;聽PMCID: PMC2644200.
  57. Gentzsch M, Chang X-B, Cui L, Wu Y, Ozols VV, Choudhury AK, Pagano RE, Riordan JR. . Mol Biol Cell. 2004 Jun;15(6):2684-96. PMID: 15075371;聽PMCID: PMC420093.
  58. Gentzsch M, Cui L, Mengos A, Chang XB, Chen JH, Riordan JR. . J Biol Chem. 2003 Feb 21;278(8):6440-9. PMID: 12471024.
  59. Gentzsch M, Aleksandrov A, Aleksandrov L, Riordan JR. . Biochem J. 2002 Sep 1;366(Pt 2):541-8. PMID: 12020354;聽PMCID: PMC1222794.
  60. Gentzsch M, Riordan JR. . J Biol Chem. 2001 Jan 12;276(2):1291-8. PMID: 11022033.

Complete Bibliography:

Headshot of Martina Gentzsch