Sanda Despa, Ph.D.

Research Description: 

Research in my lab focuses on ion transport and electrical activity of the heart. In particular, our work is aimed at understanding mechanistically how and why ion handling by cardiac muscle cells is altered in different etiologies of heart disease and how such changes exacerbate the pathology of the disease. Ultimately, our goal is to identify novel targets for cardioprotection that are tailored to the specific etiology of the underlying heart disease.

Ongoing projects are aimed at deciphering the molecular and cellular mechanisms that underlie the ankyrin-B syndrome, an arrhythmogenic phenotype caused by loss-of-function of the cytoskeletal protein ankyrin-B, and diabetic cardiomyopathy. Our work spans from the molecular level (e.g., development of novel genetically-encoded sensors for measuring local calcium level in subcellular microdomains), to the cellular (e.g., measurements of intracellular ion concentrations, electrical currents through various ion transporters and protein localization) and whole organism level (assessment of electrical activity and contractile function of the heart). We use a combination of cutting edge and traditional approaches based on fluorescence imaging, electrophysiology, molecular biology and biochemistry techniques.

PubMed Publications: 

  • Van Steenbergen, A.;Balteau, M.;Ginion, A.;Ferté, L.;Battault, S.;Ravenstein, C.M.;Balligand, J.L.;Daskalopoulos, E.P.;Gilon, P.;Despa, F.;Despa, S.;Vanoverschelde, J.L.;Horman, S.;Koepsell, H.;Berry, G.;Hue, L.;Bertrand, L.;Beauloye, C. "Sodium-myoinositol cotransporter-1, SMIT1, mediates the production of reactive oxygen species induced by hyperglycemia in the heart." Scientific reports 7, (2017): 41166. [PubMed Link] | [ Full text ]
  • Liu, M.;Verma, N.;Peng, X.;Srodulski, S.;Morris, A.;Chow, M.;Hersh, L.B.;Chen, J.;Zhu, H.;Netea, M.G.;Margulies, K.B.;Despa, S.;Despa, F. "Hyperamylinemia Increases IL-1β Synthesis in the Heart via Peroxidative Sarcolemmal Injury." Diabetes 65, 9 (2016): 2772-83. [PubMed Link] | [ Full text ]
  • Despa, S.;Vigmond, E. "From Single Myocyte to Whole Heart: The Intricate Dance of Electrophysiology and Modeling." Circulation research 118, 2 (2016): 184-6. [PubMed Link] | [ Full text ]
  • Popescu, I.;Galice, S.;Mohler, P.J.;Despa, S. "Elevated local Ca2+ and CaMKII promote spontaneous Ca2+ release in ankyrin-B-deficient hearts." Cardiovascular research 111, 3 (2016): 287-94. [PubMed Link] | [ Full text ]
  • Clancy, C.E.;Chen-Izu, Y.;Bers, D.M.;Belardinelli, L.;Boyden, P.A.;Csernoch, L.;Despa, S.;Fermini, B.;Hool, L.C.;Izu, L.;Kass, R.S.;Lederer, W.J.;Louch, W.E.;Maack, C.;Matiazzi, A.;Qu, Z.;Rajamani, S.;Rippinger, C.M.;Sejersted, O.M.;O'Rourke, B.;Weiss, J.N.;Varró, A.;Zaza, A. "Deranged sodium to sudden death." The Journal of physiology 593, 6 (2015): 1331-45. [PubMed Link] | [ Full text ]
  • Lambert, R.;Srodulski, S.;Peng, X.;Margulies, K.B.;Despa, F.;Despa, S. "Intracellular Na+ Concentration ( Na+ i) Is Elevated in Diabetic Hearts Due to Enhanced Na+-Glucose Cotransport." Journal of the American Heart Association 4, 9 (2015): e002183. [PubMed Link] | [ Full text ]
  • Despa, S.;Shui, B.;Bossuyt, J.;Lang, D.;Kotlikoff, M.I.;Bers, D.M. "Junctional cleft Ca²⁺ i measurements using novel cleft-targeted Ca²⁺ sensors." Circulation research 115, 3 (2014): 339-47. [PubMed Link] | [ Full text ]
  • Correll, R.N.;Eder, P.;Burr, A.R.;Despa, S.;Davis, J.;Bers, D.M.;Molkentin, J.D. "Overexpression of the Na+/K+ ATPase α2 but not α1 isoform attenuates pathological cardiac hypertrophy and remodeling." Circulation research 114, 2 (2014): 249-56. [PubMed Link] | [ Full text ]
  • Despa, S.;Sharma, S.;Harris, T.R.;Dong, H.;Li, N.;Chiamvimonvat, N.;Taegtmeyer, H.;Margulies, K.B.;Hammock, B.D.;Despa, F. "Cardioprotection by controlling hyperamylinemia in a "humanized" diabetic rat model." Journal of the American Heart Association 3, 4 (2014): [PubMed Link] | [ Full text ]
  • Avkiran, M.;Despa, S.;Shattock, M.J. "The salt of the earth: focus on Na⁺ regulation in the cardiac myocyte." Journal of molecular and cellular cardiology 61, (2013): 1. [PubMed Link] | [ Full text ]
  • Pavlovic, D.;Hall, A.R.;Kennington, E.J.;Aughton, K.;Boguslavskyi, A.;Fuller, W.;Despa, S.;Bers, D.M.;Shattock, M.J. "Nitric oxide regulates cardiac intracellular Na⁺ and Ca²⁺ by modulating Na/K ATPase via PKCε and phospholemman-dependent mechanism." Journal of molecular and cellular cardiology 61, (2013): 164-71. [PubMed Link] | [ Full text ]
  • Despa, S.;Bers, D.M. "Na⁺ transport in the normal and failing heart - remember the balance." Journal of molecular and cellular cardiology 61, (2013): 2-10. [PubMed Link] | [ Full text ]
  • Despa, S.;Lingrel, J.B.;Bers, D.M. "Na(+)/K)+)-ATPase α2-isoform preferentially modulates Ca2(+) transients and sarcoplasmic reticulum Ca2(+) release in cardiac myocytes." Cardiovascular research 95, 4 (2012): 480-6. [PubMed Link] | [ Full text ]
  • Guglielmino, K.;Jackson, K.;Harris, T.R.;Vu, V.;Dong, H.;Dutrow, G.;Evans, J.E.;Graham, J.;Cummings, B.P.;Havel, P.J.;Chiamvimonvat, N.;Despa, S.;Hammock, B.D.;Despa, F. "Pharmacological inhibition of soluble epoxide hydrolase provides cardioprotection in hyperglycemic rats." American journal of physiology. Heart and circulatory physiology 303, 7 (2012): H853-62. [PubMed Link] | [ Full text ]
  • Camors, E.;Mohler, P.J.;Bers, D.M.;Despa, S. "Ankyrin-B reduction enhances Ca spark-mediated SR Ca release promoting cardiac myocyte arrhythmic activity." Journal of molecular and cellular cardiology 52, 6 (2012): 1240-8. [PubMed Link] | [ Full text ]
  • Despa, S.;Margulies, K.B.;Chen, L.;Knowlton, A.A.;Havel, P.J.;Taegtmeyer, H.;Bers, D.M.;Despa, F. "Hyperamylinemia contributes to cardiac dysfunction in obesity and diabetes: a study in humans and rats." Circulation research 110, 4 (2012): 598-608. [PubMed Link] | [ Full text ]
  • Khafaga, M.;Bossuyt, J.;Mamikonian, L.;Li, J.C.;Lee, L.L.;Yarov-Yarovoy, V.;Despa, S.;Bers, D.M. "Na⁺/K⁺-ATPase E960 and phospholemman F28 are critical for their functional interaction." Proceedings of the National Academy of Sciences of the United States of America 109, 50 (2012): 20756-61. [PubMed Link] | [ Full text ]
  • Sato, D.;Despa, S.;Bers, D.M. "Can the sodium-calcium exchanger initiate or suppress calcium sparks in cardiac myocytes?" Biophysical journal 102, 8 (2012): L31-3. [PubMed Link] | [ Full text ]
  • Han, F.;Bossuyt, J.;Martin, J.L.;Despa, S.;Bers, D.M. "Role of phospholemman phosphorylation sites in mediating kinase-dependent regulation of the Na+-K+-ATPase." American journal of physiology. Cell physiology 299, 6 (2010): C1363-9. [PubMed Link] | [ Full text ]
  • Bossuyt, J.;Despa, S.;Han, F.;Hou, Z.;Robia, S.L.;Lingrel, J.B.;Bers, D.M. "Isoform specificity of the Na/K-ATPase association and regulation by phospholemman." The Journal of biological chemistry 284, 39 (2009): 26749-57. [PubMed Link] | [ Full text ]
  • Han, F.;Tucker, A.L.;Lingrel, J.B.;Despa, S.;Bers, D.M. "Extracellular potassium dependence of the Na+-K+-ATPase in cardiac myocytes: isoform specificity and effect of phospholemman." American journal of physiology. Cell physiology 297, 3 (2009): C699-705. [PubMed Link] | [ Full text ]
  • Bers, D.M.;Despa, S. "Na/K-ATPase--an integral player in the adrenergic fight-or-flight response." Trends in cardiovascular medicine 19, 4 (2009): 111-8. [PubMed Link] | [ Full text ]
  • Bers, D.M.;Despa, S. "Na+ transport in cardiac myocytes; Implications for excitation-contraction coupling." IUBMB life 61, 3 (2009): 215-21. [PubMed Link] | [ Full text ]
  • Despa, S.;Tucker, A.L.;Bers, D.M. "Phospholemman-mediated activation of Na/K-ATPase limits Na i and inotropic state during beta-adrenergic stimulation in mouse ventricular myocytes." Circulation 117, 14 (2008): 1849-55. [PubMed Link] | [ Full text ]
  • Despa, S.;Bers, D.M. "Functional analysis of Na+/K+-ATPase isoform distribution in rat ventricular myocytes." American journal of physiology. Cell physiology 293, 1 (2007): C321-7. [PubMed Link] | [ Full text ]
  • Berry, R.G.;Despa, S.;Fuller, W.;Bers, D.M.;Shattock, M.J. "Differential distribution and regulation of mouse cardiac Na+/K+-ATPase alpha1 and alpha2 subunits in T-tubule and surface sarcolemmal membranes." Cardiovascular research 73, 1 (2007): 92-100. [PubMed Link] | [ Full text ]
  • Bossuyt, J.;Despa, S.;Martin, J.L.;Bers, D.M. "Phospholemman phosphorylation alters its fluorescence resonance energy transfer with the Na/K-ATPase pump." The Journal of biological chemistry 281, 43 (2006): 32765-73. [PubMed Link] | [ Full text ]
  • Bers, D.M.;Despa, S.;Bossuyt, J. "Regulation of Ca2+ and Na+ in normal and failing cardiac myocytes." Annals of the New York Academy of Sciences 1080, (2006): 165-77. [PubMed Link] | [ Full text ]
  • Han, F.;Bossuyt, J.;Despa, S.;Tucker, A.L.;Bers, D.M. "Phospholemman phosphorylation mediates the protein kinase C-dependent effects on Na+/K+ pump function in cardiac myocytes." Circulation research 99, 12 (2006): 1376-83. [PubMed Link] | [ Full text ]
  • Bers, D.M.;Despa, S. "Cardiac myocytes Ca2+ and Na+ regulation in normal and failing hearts." Journal of pharmacological sciences 100, 5 (2006): 315-22. [PubMed Link] |
  • Brette, F.;Despa, S.;Bers, D.M.;Orchard, C.H. "Spatiotemporal characteristics of SR Ca(2+) uptake and release in detubulated rat ventricular myocytes." Journal of molecular and cellular cardiology 39, 5 (2005): 804-12. [PubMed Link] | [ Full text ]
  • Baron, S.;Caplanusi, A.;Ven, M.;Radu, M.;Despa, S.;Lambrichts, I.;Ameloot, M.;Steels, P.;Smets, I. "Role of mitochondrial Na+ concentration, measured by CoroNa red, in the protection of metabolically inhibited MDCK cells." Journal of the American Society of Nephrology : JASN 16, 12 (2005): 3490-7. [PubMed Link] | [ Full text ]
  • Despa, S.;Bossuyt, J.;Han, F.;Ginsburg, K.S.;Jia, L.G.;Kutchai, H.;Tucker, A.L.;Bers, D.M. "Phospholemman-phosphorylation mediates the beta-adrenergic effects on Na/K pump function in cardiac myocytes." Circulation research 97, 3 (2005): 252-9. [PubMed Link] | [ Full text ]
  • Despa, S.;Kockskämper, J.;Blatter, L.A.;Bers, D.M. "Na/K pump-induced Na (i) gradients in rat ventricular myocytes measured with two-photon microscopy." Biophysical journal 87, 2 (2004): 1360-8. [PubMed Link] | [ Full text ]
  • Smets, I.;Caplanusi, A.;Despa, S.;Molnar, Z.;Radu, M.;Ven, M.;Ameloot, M.;Steels, P. "Ca2+ uptake in mitochondria occurs via the reverse action of the Na+/Ca2+ exchanger in metabolically inhibited MDCK cells." American journal of physiology. Renal physiology 286, 4 (2004): F784-94. [PubMed Link] | [ Full text ]
  • Bers, D.M.;Barry, W.H.;Despa, S. "Intracellular Na+ regulation in cardiac myocytes." Cardiovascular research 57, 4 (2003): 897-912. [PubMed Link] |
  • Despa, S.;Bers, D.M. "Na/K pump current and Na (i) in rabbit ventricular myocytes: local Na (i) depletion and Na buffering." Biophysical journal 84, 6 (2003): 4157-66. [PubMed Link] | [ Full text ]
  • Ginsburg, K.S.;Weber, C.R.;Despa, S.;Bers, D.M. "Simultaneous measurement of Na i, Ca i, and I(NCX) in intact cardiac myocytes." Annals of the New York Academy of Sciences 976, (2002): 157-8. [PubMed Link] | [ Full text ]
  • Despa, S.;Islam, M.A.;Weber, C.R.;Pogwizd, S.M.;Bers, D.M. "Intracellular Na(+) concentration is elevated in heart failure but Na/K pump function is unchanged." Circulation 105, 21 (2002): 2543-8. [PubMed Link] | [ Full text ]
  • Despa, S.;Islam, M.A.;Pogwizd, S.M.;Bers, D.M. "Intracellular Na+ and Na+ pump rate in rat and rabbit ventricular myocytes." The Journal of physiology 539, Pt 1 (2002): 133-43. [PubMed Link] | [ Full text ]
  • Cooper, A. "A Case of Aneurism of the Carotid Artery." Medico-chirurgical transactions 1, (-1): 1-12.1. [PubMed Link] |