Julie Bossuyt

image of Julie Bossuyt

Associate Professor

Departments

Pharmacology, School of Medicine

Offices and Labs

530-754-7419
530-752-3874

Profile Introduction

My educational background spans the fields of molecular biology, biochemistry, physiology and veterinary medicine. This multi-disciplinary aspect is key to the lab's research approach of interweaving in vivo methods such as transgenic and surgical animal models of disease with molecular imaging of fluorescent biosensors. Over the past few years one of the research foci in my lab is the molecular mechanisms that drive activation and function of the related kinases, protein kinase D (PKD) and calmodulin dependent protein kinase (CaMKII) in healthy and failing hearts. We focus on understanding the local regulatory mechanisms that control the myriad cellular outcomes for these multifunctional kinases. Hereto we apply cutting-edge high resolution fluorescence imaging techniques (such as FRET, TIRF, FRAP and confocal) and novel biosensors to obtain unique insight into the spatiotemporal dynamics of the local Ca-CaM, CaMKII and PKD signals. This includes measurements of how Ca-CaM signals (in specific subcellular compartments) sense and decode Ca signals to shape particular cellular responses, and how CaMKII and PKD are activated in response to specific GPCR signaling pathways and by different posttranslational modifications.

Degrees

2002 PhD Physiology University of Missouri-Columbia, US
1998 DVM University of Ghent, Belgium

Research Contribution

Dr. Bossuyt has made seminal and recognized contributions in: (1) Regulation and function of cardiac protein kinase D and Ca/Calmodin dependent protein kinase II signaling, (2) Cardiac Na handling and phospholemman (PLM) regulation of the Na pump, and (3) Signaling events in cardiac hypertrophy and adverse cardiac remodeling.

ProfessionalSocieties

Belgian Veterinary Medical Association
American Heart Association
Biophysical Society
International Society for Heart Research
American Physiological Society

CBS Grad Group Affiliations

Molecular, Cellular and Integrative Physiology

Specialties / Focus

Molecular, Cellular and Integrative Physiology
  • Cardiorespiratory Physiology
  • Cellular Physiology
  • Molecular Physiology
  • Domestic Animal Physiology
  • Comparative Physiology
  • Integrative Physiology
  • Systemic Physiology

Graduate Groups not Housed in CBS

Pharmacology and Toxicology (PTX)

Publications

1/8/2018 3:55:53 PM

  • 1: Wood BM, Bossuyt J. Emergency Spatiotemporal Shift: The Response of Protein
    Kinase D to Stress Signals in the Cardiovascular System. Front Pharmacol. 2017
    Jan 24;8:9. doi: 10.3389/fphar.2017.00009. eCollection 2017. Review. PubMed PMID:
    28174535; PubMed Central PMCID: PMC5258689.


    2: Barbagallo F, Xu B, Reddy GR, West T, Wang Q, Fu Q, Li M, Shi Q, Ginsburg KS, 
    Ferrier W, Isidori AM, Naro F, Patel HH, Bossuyt J, Bers D, Xiang YK. Genetically
    Encoded Biosensors Reveal PKA Hyperphosphorylation on the Myofilaments in Rabbit 
    Heart Failure. Circ Res. 2016 Sep 30;119(8):931-43. doi:
    10.1161/CIRCRESAHA.116.308964. Epub 2016 Aug 30. PubMed PMID: 27576469; PubMed
    Central PMCID: PMC5307331.


    3: Awasthi S, Izu LT, Mao Z, Jian Z, Landas T, Lerner A, Shimkunas R, Woldeyesus 
    R, Bossuyt J, Wood B, Chen YJ, Matthews DL, Lieu DK, Chiamvimonvat N, Lam KS,
    Chen-Izu Y, Chan JW. Multimodal SHG-2PF Imaging of Microdomain Ca2+-Contraction
    Coupling in Live Cardiac Myocytes. Circ Res. 2016 Jan 22;118(2):e19-28. doi:
    10.1161/CIRCRESAHA.115.307919. Epub 2015 Dec 7. Review. PubMed PMID: 26643875;
    PubMed Central PMCID: PMC4740258.


    4: Erickson JR, Nichols CB, Uchinoumi H, Stein ML, Bossuyt J, Bers DM.
    S-Nitrosylation Induces Both Autonomous Activation and Inhibition of
    Calcium/Calmodulin-dependent Protein Kinase II δ. J Biol Chem. 2015 Oct
    16;290(42):25646-56. doi: 10.1074/jbc.M115.650234. Epub 2015 Aug 27. PubMed PMID:
    26316536; PubMed Central PMCID: PMC4646208.


    5: Pereira L, Rehmann H, Lao DH, Erickson JR, Bossuyt J, Chen J, Bers DM. Novel
    Epac fluorescent ligand reveals distinct Epac1 vs. Epac2 distribution and
    function in cardiomyocytes. Proc Natl Acad Sci U S A. 2015 Mar 31;112(13):3991-6.
    doi: 10.1073/pnas.1416163112. Epub 2015 Mar 17. PubMed PMID: 25829540; PubMed
    Central PMCID: PMC4386405.


    6: Shattock MJ, Ottolia M, Bers DM, Blaustein MP, Boguslavskyi A, Bossuyt J,
    Bridge JH, Chen-Izu Y, Clancy CE, Edwards A, Goldhaber J, Kaplan J, Lingrel JB,
    Pavlovic D, Philipson K, Sipido KR, Xie ZJ. Na+/Ca2+ exchange and Na+/K+-ATPase
    in the heart. J Physiol. 2015 Mar 15;593(6):1361-82. doi:
    10.1113/jphysiol.2014.282319. Review. PubMed PMID: 25772291; PubMed Central
    PMCID: PMC4376416.


    7: Bossuyt J. Nuclear remodelling: a consequence of nucleocytoplasmic traffic run
    amok? Cardiovasc Res. 2015 Jan 1;105(1):6-7. doi: 10.1093/cvr/cvu252. Epub 2014
    Dec 10. PubMed PMID: 25504625.


    8: Bossuyt J, Bers DM. Assessing GPCR and G protein signaling to the nucleus in
    live cells using fluorescent biosensors. Methods Mol Biol. 2015;1234:149-59. doi:
    10.1007/978-1-4939-1755-6_13. PubMed PMID: 25304355.


    9: Ljubojevic S, Radulovic S, Leitinger G, Sedej S, Sacherer M, Holzer M, Winkler
    C, Pritz E, Mittler T, Schmidt A, Sereinigg M, Wakula P, Zissimopoulos S, Bisping
    E, Post H, Marsche G, Bossuyt J, Bers DM, Kockskämper J, Pieske B. Early
    remodeling of perinuclear Ca2+ stores and nucleoplasmic Ca2+ signaling during the
    development of hypertrophy and heart failure. Circulation. 2014 Jul
    15;130(3):244-55. doi: 10.1161/CIRCULATIONAHA.114.008927. Epub 2014 Jun 13.
    PubMed PMID: 24928680; PubMed Central PMCID: PMC4101040.


    10: Despa S, Shui B, Bossuyt J, Lang D, Kotlikoff MI, Bers DM. Junctional cleft
    [Ca²⁺]i measurements using novel cleft-targeted Ca²⁺ sensors. Circ Res. 2014 Jul 
    18;115(3):339-47. doi: 10.1161/CIRCRESAHA.115.303582. Epub 2014 May 28. PubMed
    PMID: 24871564; PubMed Central PMCID: PMC4132890.


    11: Nichols CB, Chang CW, Ferrero M, Wood BM, Stein ML, Ferguson AJ, Ha D, Rigor 
    RR, Bossuyt S, Bossuyt J. β-adrenergic signaling inhibits Gq-dependent protein
    kinase D activation by preventing protein kinase D translocation. Circ Res. 2014 
    Apr 25;114(9):1398-409. doi: 10.1161/CIRCRESAHA.114.303870. Epub 2014 Mar 18.
    Erratum in: Circ Res. 2017 Apr 14;120(8):e32. Circ Res. 2017 Apr 14;120(8):e32.
    PubMed PMID: 24643961; PubMed Central PMCID: PMC4031034.


    12: Bossuyt J, Bers DM. Visualizing CaMKII and CaM activity: a paradigm of
    compartmentalized signaling. J Mol Med (Berl). 2013 Aug;91(8):907-16. doi:
    10.1007/s00109-013-1060-y. Epub 2013 Jun 18. Review. PubMed PMID: 23775230;
    PubMed Central PMCID: PMC3962229.


    13: Gold JI, Martini JS, Hullmann J, Gao E, Chuprun JK, Lee L, Tilley DG,
    Rabinowitz JE, Bossuyt J, Bers DM, Koch WJ. Nuclear translocation of cardiac G
    protein-Coupled Receptor kinase 5 downstream of select Gq-activating hypertrophic
    ligands is a calmodulin-dependent process. PLoS One. 2013;8(3):e57324. doi:
    10.1371/journal.pone.0057324. Epub 2013 Mar 5. PubMed PMID: 23472081; PubMed
    Central PMCID: PMC3589474.


    14: Lu X, Ginsburg KS, Kettlewell S, Bossuyt J, Smith GL, Bers DM. Measuring
    local gradients of intramitochondrial [Ca(2+)] in cardiac myocytes during
    sarcoplasmic reticulum Ca(2+) release. Circ Res. 2013 Feb 1;112(3):424-31. doi:
    10.1161/CIRCRESAHA.111.300501. Epub 2012 Dec 14. PubMed PMID: 23243207; PubMed
    Central PMCID: PMC3566246.


    15: Khafaga M, Bossuyt J, Mamikonian L, Li JC, Lee LL, Yarov-Yarovoy V, Despa S, 
    Bers DM. Na⁺/K⁺-ATPase E960 and phospholemman F28 are critical for their
    functional interaction. Proc Natl Acad Sci U S A. 2012 Dec 11;109(50):20756-61.
    doi: 10.1073/pnas.1207866109. Epub 2012 Nov 26. PubMed PMID: 23185013; PubMed
    Central PMCID: PMC3528502.


    16: Chang CW, Lee L, Yu D, Dao K, Bossuyt J, Bers DM. Acute β-adrenergic
    activation triggers nuclear import of histone deacetylase 5 and delays
    G(q)-induced transcriptional activation. J Biol Chem. 2013 Jan 4;288(1):192-204. 
    doi: 10.1074/jbc.M112.382358. Epub 2012 Nov 16. PubMed PMID: 23161540; PubMed
    Central PMCID: PMC3537013.


    17: Haghighi K, Pritchard T, Bossuyt J, Waggoner JR, Yuan Q, Fan GC, Osinska H,
    Anjak A, Rubinstein J, Robbins J, Bers DM, Kranias EG. The human phospholamban
    Arg14-deletion mutant localizes to plasma membrane and interacts with the
    Na/K-ATPase. J Mol Cell Cardiol. 2012 Mar;52(3):773-82. doi:
    10.1016/j.yjmcc.2011.11.012. Epub 2011 Dec 1. PubMed PMID: 22155237; PubMed
    Central PMCID: PMC3376549.


    18: Erickson JR, Patel R, Ferguson A, Bossuyt J, Bers DM. Fluorescence resonance 
    energy transfer-based sensor Camui provides new insight into mechanisms of
    calcium/calmodulin-dependent protein kinase II activation in intact
    cardiomyocytes. Circ Res. 2011 Sep 16;109(7):729-38. doi:
    10.1161/CIRCRESAHA.111.247148. Epub 2011 Aug 11. PubMed PMID: 21835909; PubMed
    Central PMCID: PMC3182829.


    19: Bossuyt J, Chang CW, Helmstadter K, Kunkel MT, Newton AC, Campbell KS, Martin
    JL, Bossuyt S, Robia SL, Bers DM. Spatiotemporally distinct protein kinase D
    activation in adult cardiomyocytes in response to phenylephrine and endothelin. J
    Biol Chem. 2011 Sep 23;286(38):33390-400. doi: 10.1074/jbc.M111.246447. Epub 2011
    Jul 27. PubMed PMID: 21795686; PubMed Central PMCID: PMC3190922.


    20: Xiang SY, Vanhoutte D, Del Re DP, Purcell NH, Ling H, Banerjee I, Bossuyt J, 
    Lang RA, Zheng Y, Matkovich SJ, Miyamoto S, Molkentin JD, Dorn GW 2nd, Brown JH. 
    RhoA protects the mouse heart against ischemia/reperfusion injury. J Clin Invest.
    2011 Aug;121(8):3269-76. doi: 10.1172/JCI44371. Epub 2011 Jul 11. PubMed PMID:
    21747165; PubMed Central PMCID: PMC3148727.


    21: Song Q, Pallikkuth S, Bossuyt J, Bers DM, Robia SL. Phosphomimetic mutations 
    enhance oligomerization of phospholemman and modulate its interaction with the
    Na/K-ATPase. J Biol Chem. 2011 Mar 18;286(11):9120-6. doi:
    10.1074/jbc.M110.198036. Epub 2011 Jan 10. PubMed PMID: 21220422; PubMed Central 
    PMCID: PMC3059012.


    22: Han F, Bossuyt J, Martin JL, Despa S, Bers DM. Role of phospholemman
    phosphorylation sites in mediating kinase-dependent regulation of the
    Na+-K+-ATPase. Am J Physiol Cell Physiol. 2010 Dec;299(6):C1363-9. doi:
    10.1152/ajpcell.00027.2010. Epub 2010 Sep 22. PubMed PMID: 20861470; PubMed
    Central PMCID: PMC3006338.


    23: Bossuyt J, Despa S, Han F, Hou Z, Robia SL, Lingrel JB, Bers DM. Isoform
    specificity of the Na/K-ATPase association and regulation by phospholemman. J
    Biol Chem. 2009 Sep 25;284(39):26749-57. doi: 10.1074/jbc.M109.047357. Epub 2009 
    Jul 28. PubMed PMID: 19638348; PubMed Central PMCID: PMC2785363.


    24: Song Q, Saucerman JJ, Bossuyt J, Bers DM. Differential integration of
    Ca2+-calmodulin signal in intact ventricular myocytes at low and high affinity
    Ca2+-calmodulin targets. J Biol Chem. 2008 Nov 14;283(46):31531-40. doi:
    10.1074/jbc.M804902200. Epub 2008 Sep 12. PubMed PMID: 18790737; PubMed Central
    PMCID: PMC2581591.


    25: Kelly EM, Hou Z, Bossuyt J, Bers DM, Robia SL. Phospholamban oligomerization,
    quaternary structure, and sarco(endo)plasmic reticulum calcium ATPase binding
    measured by fluorescence resonance energy transfer in living cells. J Biol Chem. 
    2008 May 2;283(18):12202-11. doi: 10.1074/jbc.M707590200. Epub 2008 Feb 19.
    PubMed PMID: 18287099; PubMed Central PMCID: PMC2335368.


    26: Bossuyt J, Helmstadter K, Wu X, Clements-Jewery H, Haworth RS, Avkiran M,
    Martin JL, Pogwizd SM, Bers DM. Ca2+/calmodulin-dependent protein kinase IIdelta 
    and protein kinase D overexpression reinforce the histone deacetylase 5
    redistribution in heart failure. Circ Res. 2008 Mar 28;102(6):695-702. doi:
    10.1161/CIRCRESAHA.107.169755. Epub 2008 Jan 24. PubMed PMID: 18218981.


    27: Bers DM, Despa S, Bossuyt J. Regulation of Ca2+ and Na+ in normal and failing
    cardiac myocytes. Ann N Y Acad Sci. 2006 Oct;1080:165-77. Review. PubMed PMID:
    17132783.


    28: Han F, Bossuyt J, Despa S, Tucker AL, Bers DM. Phospholemman phosphorylation 
    mediates the protein kinase C-dependent effects on Na+/K+ pump function in
    cardiac myocytes. Circ Res. 2006 Dec 8;99(12):1376-83. Epub 2006 Nov 9. PubMed
    PMID: 17095720.


    29: Bossuyt J, Despa S, Martin JL, Bers DM. Phospholemman phosphorylation alters 
    its fluorescence resonance energy transfer with the Na/K-ATPase pump. J Biol
    Chem. 2006 Oct 27;281(43):32765-73. Epub 2006 Aug 30. PubMed PMID: 16943195.


    30: Maier LS, Ziolo MT, Bossuyt J, Persechini A, Mestril R, Bers DM. Dynamic
    changes in free Ca-calmodulin levels in adult cardiac myocytes. J Mol Cell
    Cardiol. 2006 Sep;41(3):451-8. PubMed PMID: 16765983.


    31: Wu X, Zhang T, Bossuyt J, Li X, McKinsey TA, Dedman JR, Olson EN, Chen J,
    Brown JH, Bers DM. Local InsP3-dependent perinuclear Ca2+ signaling in cardiac
    myocyte excitation-transcription coupling. J Clin Invest. 2006 Mar;116(3):675-82.
    PubMed PMID: 16511602; PubMed Central PMCID: PMC1386110.


    32: Remus TP, Zima AV, Bossuyt J, Bare DJ, Martin JL, Blatter LA, Bers DM,
    Mignery GA. Biosensors to measure inositol 1,4,5-trisphosphate concentration in
    living cells with spatiotemporal resolution. J Biol Chem. 2006 Jan
    6;281(1):608-16. Epub 2005 Oct 24. PubMed PMID: 16249182.


    33: Bossuyt J, Ai X, Moorman JR, Pogwizd SM, Bers DM. Expression and
    phosphorylation of the na-pump regulatory subunit phospholemman in heart failure.
    Circ Res. 2005 Sep 16;97(6):558-65. Epub 2005 Aug 11. PubMed PMID: 16100047.


    34: Despa S, Bossuyt J, Han F, Ginsburg KS, Jia LG, Kutchai H, Tucker AL, Bers
    DM. Phospholemman-phosphorylation mediates the beta-adrenergic effects on Na/K
    pump function in cardiac myocytes. Circ Res. 2005 Aug 5;97(3):252-9. Epub 2005
    Jul 7. PubMed PMID: 16002746.


    35: Ziolo MT, Martin JL, Bossuyt J, Bers DM, Pogwizd SM. Adenoviral gene transfer
    of mutant phospholamban rescues contractile dysfunction in failing rabbit
    myocytes with relatively preserved SERCA function. Circ Res. 2005 Apr
    29;96(8):815-7. Epub 2005 Mar 24. PubMed PMID: 15790952.


    36: Ziolo MT, Maier LS, Piacentino V 3rd, Bossuyt J, Houser SR, Bers DM. Myocyte 
    nitric oxide synthase 2 contributes to blunted beta-adrenergic response in
    failing human hearts by decreasing Ca2+ transients. Circulation. 2004 Apr
    20;109(15):1886-91. Epub 2004 Mar 22. PubMed PMID: 15037528.


    37: Bossuyt J, Taylor BE, James-Kracke M, Hale CC. The cardiac sodium-calcium
    exchanger associates with caveolin-3. Ann N Y Acad Sci. 2002 Nov;976:197-204.
    PubMed PMID: 12502561.


    38: Hale CC, Bossuyt J, Hill CK, Price EM, Schulze DH, Lederer JW, Poljak R,
    Braden BC. Sodium-calcium exchange crystallization. Ann N Y Acad Sci. 2002
    Nov;976:100-2. PubMed PMID: 12502545.


    39: Bossuyt J, Taylor BE, James-Kracke M, Hale CC. Evidence for cardiac
    sodium-calcium exchanger association with caveolin-3. FEBS Lett. 2002 Jan
    30;511(1-3):113-7. PubMed PMID: 11821059.


    40: Hale CC, Hill CK, Price EM, Bossuyt J. Expressing and purifying membrane
    transport proteins in high yield. J Biochem Biophys Methods. 2002 Jan
    4;50(2-3):233-43. PubMed PMID: 11741710.