Department of Internal Medicine

Cardiovascular Medicine Faculty

Peter Mohler photo

Education:
University of North Carolina
at Chapel Hill

Postdoctoral Fellowship:
Howard Hughes Medical Institute,
Duke University Medical Center

Peter J. Mohler, Ph.D.
Associate Professor of Medicine and Molecular Physiology and Biophysics
Pew Scholar

Dr. Mohler’s laboratory is focused on understanding the cellular pathways responsible for ion channel and transporter targeting in excitable vertebrate cells.

Recent Publications

  1. Chen B, Wu Y, Mohler PJ, Anderson ME, Song LS. Local control of Ca(2+)-induced Ca(2+) release in mouse sinoatrial node cells. J Mol Cell Cardiol. 2009 Jul 15. [Epub ahead of print]
  2. Lowe JS, Palygin O, Bhasin N, Hund TJ, Boyden PA, Shibata E, Anderson ME, Mohler PJ. Voltage-gated Nav channel targeting in heart requires an ankyrin-G-dependent cellular pathway. Journal of Cell Biology, 180:173-186, 2008.
  3. Erickson JR, Joiner MA, Guan X, Kutschke W, Yang J, Oddis CV, Bartlett RK, Lowe JS, Aykin-Burns N, Zimmerman MC, Spitz DR, Colbran RJ, Shea MA, Mohler PJ, Anderson ME. A dynamic pathway for calcium-independent activation of CaMKII by methionine oxidation. Cell; 133:462-474. 2008.
  4. Le Scouarnec S, Bhasin N, Vieyres C, Hund TJ, Cunha SR, Koval O, Marionneau C, Chen B, Wu Y, Demolombe S, Song LS, Le Marec H, Probst V, Schott JJ, Anderson ME, and Mohler PJ. Dysfunction in ankyrin-B-dependent ion channel and transporter targeting causes human sinus node disease. Proc Natl Acad Sci., USA. 105:15617-15622, 2008.
  5. Cunha SR and Mohler PJ. The Cardiac Cytoskeleton and Arrhythmia: An Unexpected Role for Protein 4.1R in Cardiac Excitability. Circulation Research. 103: 779-781, 2008.
  6. Cunha SR and Mohler PJ. Obscurin targets ankyrin-B and protein phosphatase A to the cardiac M-line. The Journal of Biological Chemistry. 2008.
  7. Browne CL, Creton R, Karplus E, Mohler PJ, Palazzo RE, Miller AL. Analysis of the Ca2+ transient at nuclear envelope breakdown during the first cell cycle in dividing sea urchin eggs. Biol Bulletin, 191:5-16, 1996.
  8. Mohler PJ, Kreda SM, Boucher RC, Sudol M, Stutts MJ, Milgram SL. Yes-associated protein 65 localizes p62(c-Yes) to the apical compartment of airway epithelia by association with EBP50. The Journal of Cell Biology., 147:879-890, 1999.
  9. Goy MF, Oliver PM, Purdy KE, Knowles JW, Fox JE, Mohler PJ, Qian X, Smithies O, Maeda N. Evidence for a novel natriuretic peptide receptor that prefers brain natriuretic peptide over atrial natriuretic peptide. Biochem J., 358:379-87, 2001.
  10. Mohler PJ, Kultgen PL, Stutts MJ, Milgram SL. Biochemical assays for studying indirect interactions between CFTR and the cytoskeleton. Meth Mol Med., 70:383-394, 2002.
  11. Mohler PJ, Gramolini AO, Bennett V. Ankyrins. The Journal of Cell Science., 115:1565-1566, 2002.
  12. Mohler PJ, Gramolini AO, Bennett V. The Ankyrin-B C-terminal Domain Determines Activity of Ankyrin-B/G Chimeras in Rescue of Abnormal Inositol 1,4,5-Trisphosphate and Ryanodine Receptor Distribution in Ankyrin-B (-/-) Neonatal Cardiomyocytes. J Biol Chem., 277:10599-10607, 2002.
  13. Mohler PJ, Schott JJ, Gramolini AO, Dilly KW, Guatimosim S, DuBell WH, Song LS, Haurogne K, Kyndt F, Ali ME, Rogers TB, Lederer WJ, Escande D, LeMarec H, Bennett V. Ankyrin-B mutation causes type 4 long-QT cardiac arrhythmia and sudden cardiac death. Nature, 421:634-639, 2003.
  14. Wehrens XHT, Lehnart SE, Huang F, Vest JA, Reiken SR, Mohler PJ, Sun J, Guatimosim S, Song LS, Rosemblit N, D’Armiento JM, Napolitano C, Memmi M, Priori SG, Lederer WJ, Marks AR. FKBP12.6 deficiency and defective calcium release channel (ryanodine receptor) function linked to exercise-induced sudden cardiac death. Cell, 113:829-840, 2003.
  15. Facemire CS, Mohler PJ, Arendshorst WJ. Expression and relative abundance of short transient receptor potential channels in the rat renal microcirculation. Am J Physiol Renal Physiol., 286:F546-F551, 2004.
  16. Mohler PJ, Davis JQ, Davis LH, Hoffman JA, Michaely P, Bennett V. InsP3 receptor localization and stability in cardiomyocytes requires interaction with ankyrin-B. J Biol Chem., 279:12980-12987, 2004.
  17. Mohler PJ, Hoffman JA, Davis JQ, Abdi KM, Kim C, Jones SK, Davis LH, Roberts KF, Bennett V. Isoform specificity among ankyrins: An amphipathic alpha-helix in the divergent regulatory domain of ankyrin-B interacts with the molecular co-chaperone Hdj1/Hsp40. J Biol Chem.,279:25798-25804, 2004.
  18. Mohler PJ, Splawski I, Napolitano C, Bottelli G, Sharpe L, Timothy K, Priori SG, Keating MT, Bennett V. A cardiac arrhythmia syndrome caused by loss of ankyrin-B function. Proc Natl Acad Sci., USA; 101:9137-9142, 2004.
  19. Mohler PJ, Yoon WY, Bennett V. Ankyrin-B targets 2-spectrin to an intracellular compartment in neonatal cardiomyocytes. J Biol Chem., 279:40185-40193, 2004.
  20. Mohler PJ, Rivolta I, Napolitano C, LeMaillet G, Lambert S, Priori SG, Bennett V. Nav1.5 E1053K mutation causing Brugada Syndrome blocks binding to ankyrin-G and expression of Nav1.5 on the surface of cardiomyocytes. Proc Natl Acad Sci., USA, 101:17533-17538, 2004.
  21. Mohler PJ, and Bennett V. Ankyrin-based cardiac arrhythmia: a new class of channelopathies due to loss of cellular targeting. Curr Opin Cardiol., 20:189-193, 2005.
  22. Swift LL, Kakkad B, Boone C, Jovanovska A, Jerome WG, Mohler PJ, Ong DE. Microsomal triglyceride transfer protein (MTP) expression in adipocytes: A new component in fat metabolism. FEBS Lett., 579: 3183-3189, 2005.
  23. Mohler PJ, and Bennett V. Defects in ankyrin-based cellular pathways in metazoan physiology. Frontiers in Bioscience., 10:2832-2840, 2005.
  24. Mohler PJ, Lowe JS, Banks S. Dysfunction in ankyrin-based cellular pathways and human cardiac arrhythmia. Future Cardiol., 1:363-371, 2005.
  25. Mohler PJ, Davis JQ, Bennett V. Ankyrin-B coordinates the Na/K ATPase, Na/Ca exchanger, and InsP3 receptor in a cardiac transverse-tubule/sarcoplasmic reticulum microdomain. Public Library of Science Biology (PLOS Biology), 3:423, 2005.
  26. Abdi KM, PJ Mohler, Davis JQ, Bennett V. Isoform Specificity of Ankyrin-B: A site in the divergent C-terminal domain is required for intramolecular association. J Biol Chem., 281:5741-5749, 2006.
  27. Hodson CA, Ambrogi IG, Scott RO, Mohler PJ, Milgram SL. Polarized apical sorting of guanylyl cyclase C is specified by a cytosolic signal. Traffic, 7:1-9. 2006.
  28. Braun NA, Mohler PJ, Weisgraber KH, Hasty AH, Linton MF, Yancey PG, Su YR, Fazio S, Swift LL. Intra-cellular trafficking of recycling apolipoprotein E in Chinese hamster ovary cells. J Lipid Res., 47:1176-1186. 2006.
  29. Cunha SR, and Mohler PJ. Cardiac ankyrins: Essential components for development and maintenance of excitable membrane domains in heart. Cardiovascular Research, 71:22-29, 2006.
  30. Mohler PJ. Ankyrins and human disease: What the electrophysiologist should know. Journal of Cardiovascular Electrophysiology, 10:1153-1159. 2006.
  31. Kline CF, and Mohler PJ. Weighing in on molecular anchors: The role of ankyrins in cardiac channelopa-thies and human arrhythmia. Expert Rev Cardiovasc Ther., 4:477-485, 2006.
  32. Grueter CE, Abiria SA, Dzhura I, Wu Y, Ham AJ, Mohler PJ, Anderson ME, Colbran RJ. Calmodulin Kinase II facilitates L-type Ca2+ channels by beta subunit phosphorylation. Molecular Cell, 23:641-650, 2006.
  33. Kizhatil K, Yoon WY, Mohler PJ, Davis LH, Hoffman JA, Bennett V. Ankyrin-G and beta-2-spectrin collaborate in biogenesis of the lateral membrane of human bronchial epithelial cells. J Biol Chem.,282:2029-2037, 2007.
  34. Mohler PJ, Le Scouarnec S, Denjoy I, Lowe JS, Guicheney P, Caron L, Driskell IM, Schott JJ, Norris K, Leenhardt A, Kim RB, Escande D, Roden DM. Defining the cellular phenotype of ‘ankyrin-B syndrome’ variants: Human ANK2 variants associated with clinical phenotypes display a spectrum of activities in cardiomyocytes. Circulation, 115:432-441, 2007.
  35. Cunha SR, Bhasin N, Mohler PJ. Targeting/stability of the Na/Ca exchanger in cardiomyocytes requires direct interaction with the membrane adaptor ankyrin-B. J Biol Chem., 282:4875-4883; 2007.
  36. Bhasin N, Cunha SR, Mudannayake M, Gigena MS, Rogers TB, Mohler PJ. Molecular basis for PP2A regulatory subunit B56 alpha targeting in cardiomyocytes. Am J Physiol: Heart, 293:H109-119; 2007.
  37. Anderson ME, and Mohler PJ. MicroRNA may have macro effect on sudden death. Nature Medicine, 13:410-411; 2007.
  38. Mohler PJ, Zhu MY, Blade AM, Ham AJ, Shelness GS, Swift LL. Identification of a novel isoform of microsomal triglyceride transfer protein. J Biol Chem., 282:26981-26988,2007.
  39. Mohler PJ and Wehrens XHT. Mechanisms of human arrhythmia syndromes: Abnormal cardiac macromolecular interactions. Physiology, 22:342-350,2007.
  40. Lehnart SE, Ackerman MJ, Brugada R, Benson DW Jr, Clancey CE, Donahue JK, George AL Jr, Grant AO, Groft SC, January CT, Lathrop DA, Lederer WJ, Makielski JC, Mohler PJ, Moss A, Nerbonne JM, Olson TM, Przywara DA, Towbin JA, Wang LH, Marks AR. Inherited Arrhythmias--an NHLBI-ORD workshop consensus report about the diagnosis, phenotyping, molecular mechanisms, and therapeutic approaches for primary cardiomyopathies of gene mutations affecting ion transport function. Circulation, 116:2325-2345, 2007.
  41. Mohler PJ, Healy JA, Xue H, Puca AA, Kline CF, Allingham RR, Kranias EG, Rockman HA, Bennett V. Ankyrin-B Syndrome: Enhanced cardiac function balanced by risk of cardiac death and premature senescence. Public Library of Science (PLoS) One, 2:e1051, 2007.
  42. Li J, Marionneau C, Koval O, Zingman L, Mohler PJ, Nerbonne J, Anderson ME. Calmodulin kinase II inhibition enhances ischemic preconditioning by augmenting ATP-sensitive K+ current. Channels, 1:387-394, 2007.
  43. Lowe JS, Palygin O, Bhasin N, Hund TJ, Boyden PA, Shibata E, Anderson ME, Mohler PJ. Voltage-gated Nav channel targeting in heart requires an ankyrin-G-dependent cellular pathway. Journal of Cell Biology, 180:173-186, 2008.
  44. Sedlacek K, Stark K, Cunha SR, Pfeufer A, Weber S, Berger I, Wichmann HE, Mohler PJ, Hengstenberg C, Jeron A. Common genetic variants in ANK2 influence QT interval- results from the KORA study. Circulation: Cardiovascular Genetics. In Press.
  45. Erickson JR, Joiner MA, Guan X, Kutschke W, Yang J, Oddis CV, Bartlett RK, Lowe JS, Aykin-Burns N, Zimmerman MC, Spitz DR, Colbran RJ, Shea MA, Mohler PJ, Anderson ME. A dynamic pathway for calcium-independent activation of CaMKII by methionine oxidation. Cell; 133:462-474. 2008.
  46. Mohler PJ, and Anderson ME. New insights into genetic causes of sinus node disease and atrial fibrillation. Journal of Cardiovascular Electrophysiology, 19: 516-518, 2008.
  47. Kline CF, Cunha SR, Lowe JS, Hund TJ, Mohler PJ. Revisiting ankyrin-InsP3 receptor interactions: ankyrin-B associates with the cytoplasmic N-terminus of the InsP3 receptor. Journal of Cellular Biochemistry, 104:1244-1253, 2008.
  48. Hund TJ, Ziman AJ, Lederer WJ, and Mohler PJ. The cardiac IP3 receptor: Uncovering the role of “the other” calcium-release channel. Journal of Molecular and Cellular Cardiology, 45: 159-161, 2008.
  49. Hund TJ, Decker KF, Kanter E, Mohler PJ, Boyden PA, Schuessler RB, Yamada KA, and Rudy Y. Role of activated CaMKII in abnormal calcium homeostasis and INa remodeling after myocardial infarction: Insights from mathematical modeling. Journal of Molecular and Cellular Cardiology, 45: 420-428, 2008.
  50. Anderson ME and Mohler PJ. Chapter 4: Structural and Molecular Basis of Ion Channel Function: Intracellular Signaling and Regulation of Cardiac Ion Channels. Cardiac Electrophysiology: From Cell to Bedside 5th edition. Eds. Zipes and Jalife. Elsevier, Philadelphia, PA, 2008 (in press).
  51. Le Scouarnec S, Bhasin N, Vieyres C, Hund TJ, Cunha SR, Koval O, Marionneau C, Chen B, Wu Y, Demolombe S, Song LS, Le Marec H, Probst V, Schott JJ, Anderson ME, and Mohler PJ. Dysfunction in ankyrin-B-dependent ion channel and transporter targeting causes human sinus node disease. Proc Natl Acad Sci., USA. 105:15617-15622, 2008.
  52. Cunha SR and Mohler PJ. The Cardiac Cytoskeleton and Arrhythmia: An Unexpected Role for Protein 4.1R in Cardiac Excitability. Circulation Research.103: 779-781, 2008.
  53. Cunha, SR, Le Scouarnec S, Schott JJ, and Mohler PJ. Exon organization and novel alternative splicing of the human ANK2 gene: Implications for cardiac function and human cardiac disease. Journal of Molecular and Cellular Cardiology, In Press.
  54. Cunha SR and Mohler PJ. Obscurin targets ankyrin-B and protein phosphatase A to the cardiac M-line. The Journal of Biological Chemistry. In Press.
  55. Thiel WH, Chen B, Hund TJ, Koval OM, Purohit A, Song LS, Mohler PJ, and Anderson ME. Proarrhythmic defects in a ventricular myocyte model of Timothy Syndrome require calmodulin kinase II. Circulation, In Press.
  56. Hund TJ and Mohler PJ. Ankyrin-based targeting pathway regulates human sinoatrial node automaticity. Channels. In Press.

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