M. Jackson Stutts, PhD

Clinical Professor

Specialty Areas: Ion channel function and regulation in airway epithelia

Chronology: BS: Wake Forest University, 1971; MS: Georgia Institute of Technology, 1974; PhD: University of North Carolina, 1979; Postdoctoral: University of North Carolina, 1980-1984; Research Assistant Professor: University of North Carolina, 1984-1989; Research Associate Professor: University of North Carolina, 1989 – 1994; Associate Professor: University of North Carolina, 1994-2009; Professor: University of North Carolina: 2010-present.

Research Focus: We have long known that ENaC mediated Na+ absorption by airway epithelia of CF patients is elevated. Our lab and colleagues recently documented that the absence of functional CFTR causes abnormal stimulation of ENaC by cAMP and excessive proteolytic activation of ENaC. Presently, we are designing experiments to test the possibility that these deranged ENaC regulatory pathways are connected.

Selected Bibliography:

  1. Kota P, Gentzsch M, Dang Y, Boucher R, Stutts M. The N-terminus of alpha-ENaC mediates ENaC cleavage and activation by furin. J Gen Physiol. 2018 Aug 6;150(8):1179-1187. doi: 10.1085/jgp.201711860. PMID: 29980634. PMCID: PMC6080898.
  2. Garcia-Caballero A, Gandini MA, Huang S, Chen L, Souza IA, Dang YL, Stutts MJ, Zamponi GW. Cav3.2 calcium channel interactions with the epithelial sodium channel ENaC. Mol Brain. 2019 Feb 8;12(1):12. doi: 10.1186/s13041-019-0433-8. PMID: 30736831. PMCID: PMC6368719.
  3. Shobair M, Popov KI, Dang YL, He H, Stutts MJ, Dokholyan NV. Mapping allosteric linkage to channel gating by extracellular domains in the human epithelial sodium channel. J Biol Chem. 2018 Mar 9;293(10):3675-3684. doi: 10.1074/jbc.RA117.000604. PMID: 29358325. PMCID: PMC5846138.
  4. Reihill JA, Walker B, Hamilton RA, Ferguson TE, Elborn JS, Stutts MJ, Harvey BJ, Saint-Criq V, Hendrick SM, Martin SL. Inhibition of protease-epithelial sodium channel signaling improves mucociliary function in cystic fibrosis airways. Am J Respir Crit Care Med. 2016 Sep 15;194(6):701-10. doi: 10.1164/rccm.201511-2216OC. PMID: 27014936.
  5. Shobair M, Dagliyan O, Kota P, Dang YL, He H, Stutts MJ, Dokholyan NV. Gain-of-function mutation W493R in the epithelial sodium channel allosterically reconfigures intersubunit coupling. J Biol Chem. 2016 Feb 19;291(8):3682-92. doi: 10.1074/jbc.M115.678052. PMID: 26668308. PMCID: PMC4759151.
  6. Tan CD, Hobbs C, Sameni M, Sloane BF, Stutts MJ, Tarran R. Cathepsin B contributes to Na+ hyperabsorption in cystic fibrosis airway epithelial cultures. J Physiol. 2014 Dec 1;592(Pt 23):5251-68. doi: 10.1113/jphysiol.2013.267286. PMID: 25260629; PMCID: PMC4262337.
  7. Kota P, Buchner G, Chakraborty H, Dang YL, He H, Garcia GJ, Kubelka J, Gentzsch M, Stutts MJ, Dokholyan NV. The N-terminal domain allosterically regulates cleavage and activation of the epithelial sodium channel. J Biol Chem. 2014 Aug 15;289(33):23029-42. doi: 10.1074/jbc.M114.570952. PMID: 24973914; PMCID: PMC4132802.
  8. Hobbs CA, Blanchard MG, Alijevic O, Tan CD, Kellenberger S, Bencharit S, Cao R, Kesimer M, Walton WG, Henderson AG, Redinbo MR, Stutts MJ, Tarran R. Identification of the SPLUNC1 ENaC-inhibitory domain yields novel strategies to treat sodium hyperabsorption in cystic fibrosis airway epithelial cultures. Am J Physiol Lung Cell Mol Physiol. 2013 Dec;305(12):L990-L1001. doi: 10.1152/ajplung.00103.2013. Erratum in: Am J Physiol Lung Cell Mol Physiol. 2014 Apr 1;306(7):L708. PMID: 24124190; PMCID: PMC3882538.
  9. Garland AL, Walton WG, Coakley RD, Tan CD, Gilmore RC, Hobbs CA, Tripathy A, Clunes LA, Bencharit S, Stutts MJ, Betts L, Redinbo MR, Tarran R. Molecular basis for pH-dependent mucosal dehydration in cystic fibrosis airways. Proc Natl Acad Sci U S A. 2013 Oct 1;110(40):15973-8. doi: 10.1073/pnas.1311999110. PMID: 24043776; PMCID: PMC3791714.
  10. Tarran R, Sabater JR, Clarke TC, Tan CD, Davies CM, Liu J, Yeung A, Garland AL, Stutts MJ, Abraham WM, Phillips G, Baker WR, Wright CD, Wilbert S. Nonantibiotic macrolides prevent human neutrophil elastase-induced mucus stasis and airway surface liquid volume depletion. Am J Physiol Lung Cell Mol Physiol. 2013 Jun 1;304(11):L746-56. doi: 10.1152/ajplung.00292.2012. PMID: 23542952; PMCID: PMC3680760.
  11. Reddy MM, Stutts MJ. Status of fluid and electrolyte absorption in cystic fibrosis. Cold Spring Harb Perspect Med. 2013 Jan 1;3(1):a009555. doi: 10.1101/cshperspect.a009555. PMID: 23284077. PMCID: PMC3530040.

  12. Yu D, Thelin WR, Rogers TD, Stutts MJ, Randell SH, Grubb BR, Boucher RC. Regional differences in rat conjunctival ion transport activities. Am J Physiol Cell Physiol. 2012 Oct 1;303(7):C767-80. doi: 10.1152/ajpcell.00195.2012. PMID: 22814399; PMCID: PMC3469597.
  13. Kota P, García-Caballero A, Dang H, Gentzsch M, Stutts MJ, Dokholyan NV. Energetic and structural basis for activation of the epithelial sodium channel by matriptase. Biochemistry. 2012 Apr 24;51(16):3460-9. doi: 10.1021/bi2014773. PMID: 22471557; PMCID: PMC3404201.
  14. Garcia-Caballero A, Ishmael SS, Dang Y, Gillie D, Bond JS, Milgram SL, Stutts MJ. Activation of the epithelial sodium channel by the metalloprotease meprin β subunit. Channels (Austin). 2011 Jan-Feb;5(1):14-22. PMID: 20953144.
  15. Gentzsch M, Dang H, Dang Y, Garcia-Caballero A, Suchindran H, Boucher RC, Stutts MJ. The cystic fibrosis transmembrane conductance regulator impedes proteolytic stimulation of the epithelial Na+ channel. J Biol Chem. 2010 Oct 15;285(42):32227-32. doi: 0.1074/jbc.M110.155259.
  16. Caldwell RA, Boucher RC, Stutts MJ. Neutrophil elastase activates near-silent epithelial Na+ channels and increases airway epithelial Na+ transport. Am J Physiol Lung Cell Mol Physiol. 2005 May;288(5):L813-9. PMID: 15640288.
  17. Rossier BC, Stutts MJ. Activation of the epithelial sodium channel (ENaC) by serine proteases. Annu Rev Physiol. 2009;71:361-79. doi:10.1146/annurev.physiol.010908.163108. Review. PMID: 18928407.
  18. García-Caballero A, Dang Y, He H, Stutts MJ. ENaC proteolytic regulation by channel-activating protease 2. J Gen Physiol. 2008 Nov;132(5):521-35. doi:10.1085/jgp.200810030. PMID: 18852303; PMCID: PMC2571966.
  19. Harris M, Garcia-Caballero A, Stutts MJ, Firsov D, Rossier BC. Preferential assembly of epithelial sodium channel (ENaC) subunits in Xenopus oocytes: role of furin-mediated endogenous proteolysis. J Biol Chem. 2008 Mar 21;283(12):7455-63. doi: 10.1074/jbc.M707399200. PMID: 18195015; PMCID: PMC2276330.
  20. Thelin WR, Chen Y, Gentzsch M, Kreda SM, Sallee JL, Scarlett CO, Borchers CH, Jacobson K, Stutts MJ, Milgram SL. Direct interaction with filamins modulates the stability and plasma membrane expression of CFTR. J Clin Invest. 2007 Feb;117(2):364-74.
  21. Caldwell RA, Boucher RC, Stutts MJ. Neutrophil elastase activates near-silent epithelial Na+ channels and increases airway epithelial Na+ transport. Am J Physiol Lung Cell Mol Physiol. 2005 May;288(5):L813-9. PMID: 15640288.
  22. Barnes AP, Livera G, Huang P, Sun C, O’Neal WK, Conti M, Stutts MJ, Milgram SL. Phosphodiesterase 4D forms a cAMP diffusion barrier at the apical membrane ofthe airway epithelium. J Biol Chem. 2005 Mar 4;280(9):7997-8003. PMID: 15611099.
  23. Huang P, Gilmore E, Kultgen P, Barnes P, Milgram S, Stutts MJ. Local regulation of cystic fibrosis transmembrane regulator and epithelial sodium channel in airway epithelium. Proc Am Thorac Soc. 2004;1(1):33-7. Review. PMID: 16113409.
  24. Caldwell RA, Boucher RC, Stutts MJ. Serine protease activation of near-silent epithelial Na+ channels. Am J Physiol Cell Physiol. 2004 Jan;286(1):C190-4. PMID: 12967915.
  25. Huang P, Lazarowski ER, Tarran R, Milgram SL, Boucher RC, Stutts MJ. Compartmentalized autocrine signaling to cystic fibrosis transmembrane conductance regulator at the apical membrane of airway epithelial cells. Proc Natl Acad Sci U S A. 2001 Nov 20;98(24):14120-5. PMID: 11707576; PMCID: PMC61178.
  26. Huang P, Trotter K, Boucher RC, Milgram SL, Stutts MJ. PKA holoenzyme is functionally coupled to CFTR by AKAPs. Am J Physiol Cell Physiol. 2000 Feb;278(2):C417-22. PMID: 10666038.
  27. Short DB, Trotter KW, Reczek D, Kreda SM, Bretscher A, Boucher RC, Stutts MJ, Milgram SL. An apical PDZ protein anchors the cystic fibrosis transmembrane conductance regulator to the cytoskeleton. J Biol Chem. 1998 Jul 31;273(31):19797-801. PMID: 9677412.
  28. Gabriel SE, Brigman KN, Koller BH, Boucher RC, Stutts MJ. Cystic fibrosis heterozygote resistance to cholera toxin in the cystic fibrosis mouse model. Science. 1994 Oct 7;266(5182):107-9. PMID: 7524148.
  29. Gabriel SE, Clarke LL, Boucher RC, Stutts MJ. CFTR and outward rectifying chloride channels are distinct proteins with a regulatory relationship. Nature. 1993 May 20;363(6426):263-8. PMID: 7683773.
  30. Stutts MJ, Knowles MR, Gatzy JT, Boucher RC. Oxygen consumption and ouabain binding sites in cystic fibrosis nasal epithelium. Pediatr Res. 1986 Dec;20(12):1316-20. PMID: 2432456.
  31. Boucher RC, Stutts MJ, Knowles MR, Cantley L, Gatzy JT. Na+ transport in cystic fibrosis respiratory epithelia. Abnormal basal rate and response to adenylate cyclase activation. J Clin Invest. 1986 Nov;78(5):1245-52. PMID: 3771796; PMCID: PMC423810.
  32. Stutts MJ, Cotton CU, Yankaskas JR, Cheng E, Knowles MR, Gatzy JT, Boucher RC. Chloride uptake into cultured airway epithelial cells from cystic fibrosis patients and normal individuals. Proc Natl Acad Sci U S A. 1985 Oct;82(19):6677-81. PMID: 3863120; PMCID: PMC391273.
M Jackson Stutts