Julie Bossuyt

Julie Bossuyt

Position Title
Molecular, Cellular and Integrative Physiology Graduate Group Chair; Associate Professor

Unit
Department of Pharmacology, School of Medicine


Bio

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.

Grad Group Affiliations

  • Molecular, Cellular and Integrative Physiology
  • Pharmacology and Toxicology (PTX)

Specialties / Focus

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

Professional Societies

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

Degrees

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

Publications


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.

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