ANDREW ROBERT MARKS

Summary

Affiliation: Columbia University
Country: USA

Publications

  1. pmc Hypernitrosylated ryanodine receptor calcium release channels are leaky in dystrophic muscle
    Andrew M Bellinger
    Clyde and Helen Wu Center for Molecular Cardiology, Department of Physiology and Cellular Biophysics, Columbia University College of Physicians and Surgeons, 630 West 168th Street, New York, New York 10032, USA
    Nat Med 15:325-30. 2009
  2. pmc Leaky ryanodine receptors in β-sarcoglycan deficient mice: a potential common defect in muscular dystrophy
    Daniel C Andersson
    Department of Physiology and Cellular Biophysics, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA
    Skelet Muscle 2:9. 2012
  3. pmc Ryanodine receptor patents
    Alexander Kushnir
    Department of Medicine, Jacobi Medical Center, Albert Einstein College of Medicine, 1400 Pelham ParkwaySouth, New York, NY 10461, USA
    Recent Pat Biotechnol 6:157-66. 2012
  4. pmc Calcium cycling proteins and heart failure: mechanisms and therapeutics
    Andrew R Marks
    Department of Physiology and Cellular Biophysics and The Clyde and Helen Wu Center for Molecular Cardiology, College of Physicians and Surgeons of Columbia University, New York, New York 10032, USA
    J Clin Invest 123:46-52. 2013
  5. pmc Stress-induced increase in skeletal muscle force requires protein kinase A phosphorylation of the ryanodine receptor
    Daniel C Andersson
    Department of Physiology and Cellular Biophysics and the Clyde andHelenWu Center for Molecular Cardiology, New York, NY, USA
    J Physiol 590:6381-7. 2012
  6. pmc Calcium leak through ryanodine receptors leads to atrial fibrillation in 3 mouse models of catecholaminergic polymorphic ventricular tachycardia
    Jian Shan
    Clyde and Helen Wu Center for Molecular Cardiology, Department of Physiology, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA
    Circ Res 111:708-17. 2012
  7. pmc Phosphorylation-dependent regulation of ryanodine receptors: a novel role for leucine/isoleucine zippers
    S O Marx
    Center for Molecular Cardiology, Department of Medicine, College of Physicians and Surgeons of Columbia University, 630 West 168th St, New York, NY 10032, USA
    J Cell Biol 153:699-708. 2001
  8. ncbi request reprint Involvement of the cardiac ryanodine receptor/calcium release channel in catecholaminergic polymorphic ventricular tachycardia
    Andrew R Marks
    Center for Molecular Cardiology, Department of Pharmacology, Box 65, Columbia University College of Physicians and Surgeons, 630 West 168th Street, New York, NY 10032, USA
    J Cell Physiol 190:1-6. 2002
  9. ncbi request reprint Ryanodine receptors, FKBP12, and heart failure
    Andrew R Marks
    Center for Molecular Cardiology, Department of Medicine, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA
    Front Biosci 7:d970-7. 2002
  10. ncbi request reprint Ryanodine receptors/calcium release channels in heart failure and sudden cardiac death
    A R Marks
    Center for Molecular Cardiology, Department of Pharmacology, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA
    J Mol Cell Cardiol 33:615-24. 2001

Research Grants

  1. MOLECULAR BASIS OF HEART FAILURE
    Andrew Marks; Fiscal Year: 2006
  2. Regulation of cardiac ion channel function via allosteric modulators
    Andrew Marks; Fiscal Year: 2007
  3. CARDIAC AND SKELETAL MUSCLE CALCIUM RELEASE CHANNELS
    Andrew Marks; Fiscal Year: 2007
  4. CARDIAC AND SKELETAL MUSCLE CALCIUM RELEASE CHANNELS
    Andrew Marks; Fiscal Year: 2006
  5. Multidisciplinary Training in Translational Cardiovascular Research
    Andrew Marks; Fiscal Year: 2007
  6. Molecular Basis of Sudden Cardiac Death
    Andrew Marks; Fiscal Year: 2007
  7. CARDIAC AND SKELETAL MUSCLE CALCIUM RELEASE CHANNELS
    Andrew Marks; Fiscal Year: 2009
  8. MOLECULAR BASIS OF HEART FAILURE
    Andrew Marks; Fiscal Year: 2009
  9. MOLECULAR BASIS OF HEART FAILURE
    ANDREW ROBERT MARKS; Fiscal Year: 2010
  10. MOLECULAR BASIS OF HEART FAILURE
    Andrew Marks; Fiscal Year: 2009

Collaborators

Detail Information

Publications83

  1. pmc Hypernitrosylated ryanodine receptor calcium release channels are leaky in dystrophic muscle
    Andrew M Bellinger
    Clyde and Helen Wu Center for Molecular Cardiology, Department of Physiology and Cellular Biophysics, Columbia University College of Physicians and Surgeons, 630 West 168th Street, New York, New York 10032, USA
    Nat Med 15:325-30. 2009
    ....
  2. pmc Leaky ryanodine receptors in β-sarcoglycan deficient mice: a potential common defect in muscular dystrophy
    Daniel C Andersson
    Department of Physiology and Cellular Biophysics, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA
    Skelet Muscle 2:9. 2012
    ..This pathological intracellular calcium leak contributes to reduced calcium release and decreased muscle force production. It is unknown whether RyR1 dysfunction occurs also in other muscular dystrophies...
  3. pmc Ryanodine receptor patents
    Alexander Kushnir
    Department of Medicine, Jacobi Medical Center, Albert Einstein College of Medicine, 1400 Pelham ParkwaySouth, New York, NY 10461, USA
    Recent Pat Biotechnol 6:157-66. 2012
    ..Additionally, these patents highlight questions, controversies, and future directions of the RyR field...
  4. pmc Calcium cycling proteins and heart failure: mechanisms and therapeutics
    Andrew R Marks
    Department of Physiology and Cellular Biophysics and The Clyde and Helen Wu Center for Molecular Cardiology, College of Physicians and Surgeons of Columbia University, New York, New York 10032, USA
    J Clin Invest 123:46-52. 2013
    ..There are many potential opportunities for additional mechanism-based therapeutics involving the machinery that regulates Ca2+ cycling in the heart...
  5. pmc Stress-induced increase in skeletal muscle force requires protein kinase A phosphorylation of the ryanodine receptor
    Daniel C Andersson
    Department of Physiology and Cellular Biophysics and the Clyde andHelenWu Center for Molecular Cardiology, New York, NY, USA
    J Physiol 590:6381-7. 2012
    ..These data suggest that the molecular mechanism underlying skeletal muscle inotropy requires enhanced SR Ca(2+) release due to PKA phosphorylation of S2844 in RyR1...
  6. pmc Calcium leak through ryanodine receptors leads to atrial fibrillation in 3 mouse models of catecholaminergic polymorphic ventricular tachycardia
    Jian Shan
    Clyde and Helen Wu Center for Molecular Cardiology, Department of Physiology, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA
    Circ Res 111:708-17. 2012
    ..The ryanodine receptor (RyR2) is the major calcium (Ca2+) release channel on the sarcoplasmic reticulum (SR) required for excitation-contraction coupling in cardiac muscle...
  7. pmc Phosphorylation-dependent regulation of ryanodine receptors: a novel role for leucine/isoleucine zippers
    S O Marx
    Center for Molecular Cardiology, Department of Medicine, College of Physicians and Surgeons of Columbia University, 630 West 168th St, New York, NY 10032, USA
    J Cell Biol 153:699-708. 2001
    ....
  8. ncbi request reprint Involvement of the cardiac ryanodine receptor/calcium release channel in catecholaminergic polymorphic ventricular tachycardia
    Andrew R Marks
    Center for Molecular Cardiology, Department of Pharmacology, Box 65, Columbia University College of Physicians and Surgeons, 630 West 168th Street, New York, NY 10032, USA
    J Cell Physiol 190:1-6. 2002
    ..g., VT). We propose that RyR2 mutations linked to genetic forms of catecholaminergic-induced SCD may alter the regulation of the channel resulting in increased SR calcium leak during sympathetic stimulation...
  9. ncbi request reprint Ryanodine receptors, FKBP12, and heart failure
    Andrew R Marks
    Center for Molecular Cardiology, Department of Medicine, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA
    Front Biosci 7:d970-7. 2002
    ..The chronic hyperadrenergic state of heart failure is associated with defective Ca2+ signaling in part due to PKA hyperphosphorylation of RyR2...
  10. ncbi request reprint Ryanodine receptors/calcium release channels in heart failure and sudden cardiac death
    A R Marks
    Center for Molecular Cardiology, Department of Pharmacology, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA
    J Mol Cell Cardiol 33:615-24. 2001
    ..6 and regulates the channel open probability (P(o)). In failing human hearts RyR2 is PKA hyperphosphorylated resulting in defective channel function due to increased sensitivity to Ca2+-induced activation...
  11. ncbi request reprint Regulation of ryanodine receptors via macromolecular complexes: a novel role for leucine/isoleucine zippers
    Andrew R Marks
    Department of Medicine, Columbia University College of Physicians and Surgeons, Center for Molecular Cardiology, New York 10032, USA
    Trends Cardiovasc Med 12:166-70. 2002
    ..The components of the RyR2 macromolecular signaling complex are also novel targets for heart failure and cardiac arrhythmia therapeutics...
  12. pmc Repaving the road to biomedical innovation through academia
    Andrew R Marks
    Department of Physiology and Cellular Biophysics, Wu Center for Molecular Cardiology, College of Physicians and Surgeons of Columbia University, New York, NY 10032, USA
    Sci Transl Med 3:89cm15. 2011
    ..New models for public funding that support high-risk research in academia will spur innovation and ultimately advance clinical medicine...
  13. pmc Calcium and the heart: a question of life and death
    Andrew R Marks
    Center for Molecular Cardiology, Department of Medicine, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA
    J Clin Invest 111:597-600. 2003
  14. ncbi request reprint Rapamycin: signaling in vascular smooth muscle
    A R Marks
    Center for Molecular Cardiology, Department of Medicine, Columbia University College of Physicians and Surgeons, New York, New York, USA
    Transplant Proc 35:231S-233S. 2003
    ....
  15. pmc Physiological systems under pressure
    Andrew R Marks
    Clyde and Helen Wu Center for Molecular Cardiology, Department of Physiology and Cellular Biophysics, Columbia University College of Physicians and Surgeons, New York, New York, USA
    J Clin Invest 118:411-2. 2008
    ..However, as pointed out in many of the articles, much remains to be learned before such approaches can be envisioned...
  16. ncbi request reprint Progression of heart failure: is protein kinase a hyperphosphorylation of the ryanodine receptor a contributing factor?
    Andrew R Marks
    Center for Molecular Cardiology, Department of Pharmacology, Columbia University College of Physicians and Surgeons, New York, NY, USA
    Circulation 105:272-5. 2002
  17. ncbi request reprint Leucine/isoleucine zipper coordination of ion channel macromolecular signaling complexes in the heart. Roles in inherited arrhythmias
    R S Kass
    Department of Pharmacology Division of Cardiology, College of Physicians and Surgeons, Columbia University, 630 West 168th Street, New York, NY 10032, USA
    Trends Cardiovasc Med 13:52-6. 2003
    ..Disruption of local signaling by disease-associated LIZ mutations unbalances the physiologic response to SNS stimulation and increases the risk of arrhythmia in mutation carriers...
  18. ncbi request reprint Coupled gating between cardiac calcium release channels (ryanodine receptors)
    S O Marx
    Center for Molecular Cardiology, Department of Medicine, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA
    Circ Res 88:1151-8. 2001
    ..Coupled gating between RyR2 channels may be an important regulatory mechanism in excitation-contraction coupling as well as in other signaling pathways involving intracellular Ca(2+) release...
  19. ncbi request reprint Myocardial disease in failing hearts: defective excitation-contraction coupling
    X H Wehrens
    Center for Molecular Cardiology, Departments of Medicine and Pharmacology, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA
    Cold Spring Harb Symp Quant Biol 67:533-41. 2002
  20. ncbi request reprint Effects of rapamycin on ryanodine receptor/Ca(2+)-release channels from cardiac muscle
    E Kaftan
    Department of Physiology, Universtiy of Connecticut, Mount Sinai School of Medicine, New York, NY, USA
    Circ Res 78:990-7. 1996
    ....
  21. ncbi request reprint PKA phosphorylation dissociates FKBP12.6 from the calcium release channel (ryanodine receptor): defective regulation in failing hearts
    S O Marx
    Center for Molecular Cardiology, Department of Medicine, College of Physicians and Surgeons of Columbia University, New York, New York 10032, USA
    Cell 101:365-76. 2000
    ..6, PKA, the protein phosphatases PP1 and PP2A, and an anchoring protein, mAKAP. In failing human hearts, RyR2 is PKA hyperphosphorylated, resulting in defective channel function due to increased sensitivity to Ca2+-induced activation...
  22. ncbi request reprint FKBP12 binding modulates ryanodine receptor channel gating
    M Gaburjakova
    Center for Molecular Cardiology and Department of Medicine, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA
    J Biol Chem 276:16931-5. 2001
    ..6, an isoform of FKBP12. These data identify Val2461 as a critical residue required for FKBP12 binding to RyR1 and demonstrate the functional role for FKBP12 in the RyR1 channel complex...
  23. pmc Rapamycin inhibits vascular smooth muscle cell migration
    M Poon
    Cardiovascular Institute, Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029, USA
    J Clin Invest 98:2277-83. 1996
    ..0001). Thus, in addition to being a potent immunosuppressant and antiproliferative, rapamycin also inhibits SMC migration...
  24. ncbi request reprint Chronic unloading by left ventricular assist device reverses contractile dysfunction and alters gene expression in end-stage heart failure
    P M Heerdt
    Departments of Medicine, Surgery, and Biomedical Engineering, Columbia University, New York, NY, USA
    Circulation 102:2713-9. 2000
    ....
  25. ncbi request reprint Intracellular calcium release channel expression during embryogenesis
    N Rosemblit
    Molecular Cardiology Program, Divisions of Circulatory Physiology and Cardiology, Department of Medicine, New York, New York, 10032, USA
    Dev Biol 206:163-77. 1999
    ....
  26. ncbi request reprint FK506 binding protein associated with the calcium release channel (ryanodine receptor)
    T Jayaraman
    Department of Medicine, Mount Sinai School of Medicine, New York, New York 10029
    J Biol Chem 267:9474-7. 1992
    ..The molar ratio of FKBP12 to RyRec in highly purified RyRec preparations is approximately 1:4, indicating that one FKBP12 molecule is associated with each calcium release channel/foot structure...
  27. ncbi request reprint beta-adrenergic receptor blockers restore cardiac calcium release channel (ryanodine receptor) structure and function in heart failure
    S Reiken
    Center for Molecular Cardiology, Department of Pharmacology, Circulatory Physiology Division, Department of Medicine, Columbia University College of Physicians and Surgeons, New York, NY, USA
    Circulation 104:2843-8. 2001
    ..CONCLUSIONS: These results may, in part, explain the improved cardiac function observed in heart failure patients treated with beta-adrenergic receptor blockers...
  28. ncbi request reprint Role for p27(Kip1) in Vascular Smooth Muscle Cell Migration
    J Sun
    Cardiology Division, Center for Molecular Cardiology, Department of Medicine, Columbia University College of Physicians and Surgeons, Mount Sinai School of Medicine, New York, NY, USA
    Circulation 103:2967-72. 2001
    ..We hypothesized that the antimigratory effect of rapamycin may also be mediated by p27(Kip1)...
  29. pmc A novel ryanodine receptor mutation linked to sudden death increases sensitivity to cytosolic calcium
    Albano C Meli
    Department of Physiology and Cellular Biophysics, Clyde and Helen Wu Center for Molecular Cardiology, College of Physicians and Surgeons of Columbia University, New York, NY, USA
    Circ Res 109:281-90. 2011
    ..CPVT-associated RyR2 mutations cause fatal ventricular arrhythmias in young individuals during β-adrenergic stimulation...
  30. ncbi request reprint The human type 1 inositol 1,4,5-trisphosphate receptor from T lymphocytes. Structure, localization, and tyrosine phosphorylation
    D J Harnick
    Department of Medicine, Mount Sinai School of Medicine, New York, New York 10029
    J Biol Chem 270:2833-40. 1995
    ..During T cell activation the IP3R was tyrosine phosphorylated. A site-specific anti-IP3R antibody was used to localize the carboxyl terminus of the IP3R to the cytoplasm in T cells...
  31. ncbi request reprint Cellular functions of immunophilins
    A R Marks
    Laboratory of Molecular Cardiology, Cardiovascular Institute, Department of Medicine, Mount Sinai School of Medicine, New York, USA
    Physiol Rev 76:631-49. 1996
    ..In each case, FKBPs modulate channel function possibly by enhancing the cooperativity between subunits...
  32. pmc A computational model of Purkinje fibre single cell electrophysiology: implications for the long QT syndrome
    K J Sampson
    Department of Pharmacology, College of Physicians and Surgeons of Columbia University, New York, NY 10032, USA
    J Physiol 588:2643-55. 2010
    ..This new Purkinje cellular model can be a useful tool to study tissue-specific drug interactions and the effects of disease-related ion channel dysfunction on the cardiac conduction system...
  33. ncbi request reprint Intracellular calcium-release channels: regulators of cell life and death
    A R Marks
    Cardiovascular Institute, Department of Medicine, Mount Sinai School of Medicine, New York, New York 10029, USA
    Am J Physiol 272:H597-605. 1997
    ..Thus RyRs and IP3Rs play critical roles in fundamental and diverse signaling phenomena that include excitation-contraction coupling, T-cell activation, and programmed cell death...
  34. pmc Enhancing calstabin binding to ryanodine receptors improves cardiac and skeletal muscle function in heart failure
    Xander H T Wehrens
    Department of Physiology and Cellular Biophysics, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA
    Proc Natl Acad Sci U S A 102:9607-12. 2005
    ..We conclude that JTV519 may provide a specific way to treat the cardiac and skeletal muscle myopathy in HF by increasing calstabin binding to RyR...
  35. ncbi request reprint Novel therapy for heart failure and exercise-induced ventricular tachycardia based on 'fixing' the leak in ryanodine receptors
    Andrew R Marks
    Clyde and Helen Wu Center for Molecular Cardiology, Department of Physiology and Cellular Biophysics, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA
    Novartis Found Symp 274:132-47; discussion 147-55, 272-6. 2006
    ..Therefore, this class of compounds has tremendous potential as novel therapeutics for heart failure and cardiac arrhythmias...
  36. pmc Profile of Andrew R. Marks
    Philip Downey
    Proc Natl Acad Sci U S A 103:8915-7. 2006
  37. pmc Stabilization of cardiac ryanodine receptor prevents intracellular calcium leak and arrhythmias
    Stephan E Lehnart
    Department of Physiology, Clyde and Helen Wu Center for Molecular Cardiology, Columbia University, New York, NY 10032, USA
    Proc Natl Acad Sci U S A 103:7906-10. 2006
    ..Our data suggest that calstabin-2 deficiency is as a critical mediator of triggers that initiate cardiac arrhythmias...
  38. pmc Analysis of calstabin2 (FKBP12.6)-ryanodine receptor interactions: rescue of heart failure by calstabin2 in mice
    Fannie Huang
    Clyde and Helen Wu Center for Molecular Cardiology, Department of Physiology and Cellular Biophysics, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA
    Proc Natl Acad Sci U S A 103:3456-61. 2006
    ..Furthermore, using wild-type and genetically altered murine models of heart failure induced by myocardial infarction, we show that manipulating the stoichiometry between calstabin2 and RyR2 can restore normal cardiac function in vivo...
  39. pmc Ryanodine receptor/calcium release channel PKA phosphorylation: a critical mediator of heart failure progression
    Xander H T Wehrens
    Department of Physiology and Cellular Biophysics, Clyde and Helen Wu Center for Molecular Cardiology, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA
    Proc Natl Acad Sci U S A 103:511-8. 2006
    ..Taken together, these data show that PKA phosphorylation of Ser-2808 on the RyR2 channel appears to be a critical mediator of progressive cardiac dysfunction after myocardial infarction...
  40. pmc Phosphodiesterase 4D deficiency in the ryanodine-receptor complex promotes heart failure and arrhythmias
    Stephan E Lehnart
    Clyde and Helen Wu Center for Molecular Cardiology, Department of Physiology and Cellular Biophysics, College of Physicians and Surgeons of Columbia University, New York, NY 10032, USA
    Cell 123:25-35. 2005
    ..These data suggest that reduced PDE4D activity causes defective RyR2-channel function associated with heart failure and arrhythmias...
  41. ncbi request reprint Ryanodine receptor-targeted anti-arrhythmic therapy
    Xander H T Wehrens
    Department of Physiology and Cellular Biophysics, Center for Molecular Cardiology, College of Physicians and Surgeons of Columbia University, New York, New York 10032, USA
    Ann N Y Acad Sci 1047:366-75. 2005
    ....
  42. pmc A mechanism for sudden infant death syndrome (SIDS): stress-induced leak via ryanodine receptors
    David J Tester
    Department of Medicine, Division of Cardiovascular Diseases, Mayo Clinic College of Medicine, Rochester, Minnesota 55901, USA
    Heart Rhythm 4:733-9. 2007
    ..Mutations in the RyR2-encoded cardiac ryanodine receptor cause the highly lethal catecholaminergic polymorphic ventricular tachycardia (CPVT1) in the young...
  43. doi request reprint Nonshivering thermogenesis protects against defective calcium handling in muscle
    Jan Aydin
    Department of Physiology and Pharmacology, Karolinska Institutet, 171 77 Stockholm, Sweden
    FASEB J 22:3919-24. 2008
    ..These results indicate that activation of UCP1-mediated heat production in brown adipose tissue during cold exposure reduces the necessity for shivering and thus prevents the development of severe dysfunction in shivering muscles...
  44. pmc Arrhythmogenic right ventricular cardiomyopathy in Boxer dogs is associated with calstabin2 deficiency
    Mark A Oyama
    University of Pennsylvania, Philadelphia, PA, USA, USA
    J Vet Cardiol 10:1-10. 2008
    ..To examine the presence and effect of calstabin2-deficiency in Boxer dogs with arrhythmogenic right ventricular cardiomyopathy (ARVC)...
  45. pmc Stressed out: the skeletal muscle ryanodine receptor as a target of stress
    Andrew M Bellinger
    Clyde and Helen Wu Center for Molecular Cardiology, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA
    J Clin Invest 118:445-53. 2008
    ..Here, we address current understandings of the altered regulation of SR Ca(2+) release during chronic stress, focusing on the role of the SR Ca(2+) release channel known as the type 1 ryanodine receptor...
  46. ncbi request reprint Modulation of the ryanodine receptor and intracellular calcium
    Ran Zalk
    Department of Physiology and Cellular Biophysics, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA
    Annu Rev Biochem 76:367-85. 2007
    ..This review focuses on recent progress in the understanding of RyR regulation and disease mechanisms that are associated with channel dysfunction...
  47. pmc A function for tyrosine phosphorylation of type 1 inositol 1,4,5-trisphosphate receptor in lymphocyte activation
    Nikhil deSouza
    Department of Physiology and Cellular Biophysics, Clyde and Helen Wu Center for Molecular Cardiology, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA
    J Cell Biol 179:923-34. 2007
    ..Thus, tyrosine phosphorylation of IP3R1-Y353 may have an important function in maintaining elevated cytosolic Ca2+ levels during lymphocyte activation...
  48. ncbi request reprint Heart failure and sudden cardiac death: causes and cures
    Andrew R Marks
    Clyde and Helen Wu Center for Molecular Cardiology, Department of Physiology and Cellular Biophysics, College of Physicians and Surgeons, Columbia University, New York, New York, USA
    Harvey Lect 101:39-57. 2005
  49. ncbi request reprint Inherited arrhythmias: a National Heart, Lung, and Blood Institute and Office of Rare Diseases workshop consensus report about the diagnosis, phenotyping, molecular mechanisms, and therapeutic approaches for primary cardiomyopathies of gene mutations affe
    Stephan E Lehnart
    Department of Physiology and Cellular Biophysics, Clyde and Helen Wu Center for Molecular Cardiology, College of Physicians and Surgeons of Columbia University, P and S 9 401 box 22, 630 W 168 St, New York, NY 10032, USA
    Circulation 116:2325-45. 2007
    ....
  50. ncbi request reprint Regulation of ryanodine receptors in the heart
    Stephan Lehnart
    Circ Res 101:746-9. 2007
  51. ncbi request reprint Defective cardiac ryanodine receptor regulation during atrial fibrillation
    John A Vest
    Department of Physiology and Cellular Biophysics, Clyde and Helen Wu Center for Molecular Cardiology, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA
    Circulation 111:2025-32. 2005
    ..6) causes SR Ca2+ leak in failing hearts and can trigger fatal ventricular arrhythmias. Little is known about the role of RyR2 dysfunction in AF, however...
  52. ncbi request reprint Left ventricular assist device support normalizes left and right ventricular beta-adrenergic pathway properties
    Stefan Klotz
    Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, New York, USA
    J Am Coll Cardiol 45:668-76. 2005
    ..We hypothesized that some aspects of left ventricular assist device (LVAD) reverse remodeling could be independent of hemodynamic factors and would primarily depend upon normalization of neurohormonal milieu...
  53. ncbi request reprint The endoplasmic reticulum is the site of cholesterol-induced cytotoxicity in macrophages
    Bo Feng
    Department of Medicine, Columbia University, New York, NY 10032, USA
    Nat Cell Biol 5:781-92. 2003
    ..We propose that cholesterol trafficking to endoplasmic reticulum membranes, resulting in activation of the CHOP arm of the UPR, is the key signalling step in cholesterol-induced apoptosis in macrophages...
  54. ncbi request reprint Immunophilins and coupled gating of ryanodine receptors
    Stephan E Lehnart
    Center for Molecular Cardiology, Columbia University College of Physicians and Surgeons, 630 West 168th Street, New York, N Y 10032, USA
    Curr Top Med Chem 3:1383-91. 2003
    ....
  55. ncbi request reprint FKBP12.6 deficiency and defective calcium release channel (ryanodine receptor) function linked to exercise-induced sudden cardiac death
    Xander H T Wehrens
    Department of Physiology and Cellular Biophysics, Center for Molecular Cardiology, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA
    Cell 113:829-40. 2003
    ..6 for RyR2 and increased single-channel activity under conditions that simulate exercise. These data suggest that "leaky" RyR2 channels can trigger fatal cardiac arrhythmias, providing a possible explanation for CPVT...
  56. ncbi request reprint Beta-blockers restore calcium release channel function and improve cardiac muscle performance in human heart failure
    Steven Reiken
    Center for Molecular Cardiology, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA
    Circulation 107:2459-66. 2003
    ..6. We tested the hypothesis that improved cardiac muscle function attributable to beta-AR blockade is associated with restoration of normal RyR2 channel function in patients with heart failure...
  57. ncbi request reprint Use of rapamycin slows progression of cardiac transplantation vasculopathy
    Donna Mancini
    Columbia University, New York, NY, USA
    Circulation 108:48-53. 2003
    ..We investigated whether rapamycin could prevent progression of graft vasculopathy in 46 patients (age, 54+/-10 years; 4.3+/-2.3 years after transplantation) with severe disease...
  58. ncbi request reprint A guide for the perplexed: towards an understanding of the molecular basis of heart failure
    Andrew R Marks
    Circulation 107:1456-9. 2003
  59. pmc PKA phosphorylation activates the calcium release channel (ryanodine receptor) in skeletal muscle: defective regulation in heart failure
    Steven Reiken
    Center for Molecular Cardiology, Box 65, Columbia University College of Physicians and Surgeons, Room 9 401, 630 West 168th Street, New York, NY 10032, USA
    J Cell Biol 160:919-28. 2003
    ..PKA hyperphosphorylation of RyR1 may contribute to impaired skeletal muscle function in HF, suggesting that a generalized EC coupling myopathy may play a role in HF...
  60. ncbi request reprint Arrhythmias of the heart: beyond ion channels
    Andrew R Marks
    Nat Med 9:263-4. 2003
  61. ncbi request reprint Regulation of the ryanodine receptor in heart failure
    Steven O Marx
    Center for Molecular Cardiology, Division of Cardiology, Department of Medicine, Columbia University College of Physicians and Surgeons, Rm 9 401, 630 West 168th Street, New York, NY 10032, USA
    Basic Res Cardiol 97:I49-51. 2002
    ..6 and regulates the open probability of the channel. In failing hearts, RyR2 is PKA hyperphosphorylated resulting in defective channel function due to increased sensitivity to Ca2+ induced activation...
  62. ncbi request reprint Protein kinase A phosphorylation of the cardiac calcium release channel (ryanodine receptor) in normal and failing hearts. Role of phosphatases and response to isoproterenol
    Steven Reiken
    Center for Molecular Cardiology, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA
    J Biol Chem 278:444-53. 2003
    ....
  63. ncbi request reprint Protein kinase A and two phosphatases are components of the inositol 1,4,5-trisphosphate receptor macromolecular signaling complex
    Nikhil deSouza
    Center for Molecular Cardiology, Department of Medicine, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA
    J Biol Chem 277:39397-400. 2002
    ..PKA phosphorylation of IP3R1 increases channel activity in planar lipid bilayers. These studies indicate that regulation of IP3R1 function via PKA phosphorylation involves components of a macromolecular signaling complex...
  64. ncbi request reprint Clinical implications of cardiac ryanodine receptor/calcium release channel mutations linked to sudden cardiac death
    Andrew R Marks
    Circulation 106:8-10. 2002
  65. ncbi request reprint Altered function and regulation of cardiac ryanodine receptors in cardiac disease
    Xander H T Wehrens
    Center for Molecular Cardiology, Departments of Physiology and Cellular Biophysics and Medicine, Columbia University College of Physicians and Surgeons, 630W 168th Street, P and S 9 401, Box 65, New York, NY 10032, USA
    Trends Biochem Sci 28:671-8. 2003
    ..Thus, defects in RyR2 have been linked to heart failure and exercise-induced sudden cardiac death and might provide novel therapeutic targets for the treatment of these common diseases of the heart...
  66. ncbi request reprint Requirement of a macromolecular signaling complex for beta adrenergic receptor modulation of the KCNQ1-KCNE1 potassium channel
    Steven O Marx
    Department of Pharmacology, Center for Molecular Cardiology, Department of Medicine, College of Physicians and Surgeons of Columbia University, New York, NY 10032, USA
    Science 295:496-9. 2002
    ..Yotiao binds to hKCNQ1 by a leucine zipper motif, which is disrupted by an LQTS mutation (hKCNQ1-G589D). Identification of the hKCNQ1 macromolecular complex provides a mechanism for SNS modulation of cardiac APD through IKS...
  67. ncbi request reprint Calstabin deficiency, ryanodine receptors, and sudden cardiac death
    Stephan E Lehnart
    Department of Physiology and Cellular Biophysics, Center for Molecular Cardiology, Columbia University College of Physicians and Surgeons, 630W 168th Street, P and S 9 401, New York, NY 10032, USA
    Biochem Biophys Res Commun 322:1267-79. 2004
    ....
  68. ncbi request reprint Sudden death in familial polymorphic ventricular tachycardia associated with calcium release channel (ryanodine receptor) leak
    Stephan E Lehnart
    Center for Molecular Cardiology, Department of Physiology and Cellular Biophysics, Columbia University College of Physicians and Surgeons, 630 W 168th St, P and S 9 401, Box 65, New York, NY 10032, USA
    Circulation 109:3208-14. 2004
    ....
  69. ncbi request reprint Intracellular calcium release and cardiac disease
    Xander H T Wehrens
    Department of Physiology and Cellular Biophysics, Center for Molecular Cardiology, Department of Medicine, Columbia University College of Physicians and Surgeons, New York 10032, USA
    Annu Rev Physiol 67:69-98. 2005
    ..The chronically activated fight or flight response leads to leaky channels, altered calcium signaling, and contractile dysfunction and cardiac arrhythmias...
  70. ncbi request reprint Molecular determinants of altered contractility in heart failure
    Xander H T Wehrens
    Center for Molecular Cardiology, Department of Physiology and Cellular Biophysics, Columbia University College of Physicians and Surgeons, 630W 168th Street, P and S 9 401, Box 65, New York, NY 10032, USA
    Ann Med 36:70-80. 2004
    ..In conclusion, chronic hyperactivity of the beta-adrenergic signaling pathway impairs intracellular Ca2+ handling, which leads to reduced contractility in patients with heart failure...
  71. ncbi request reprint Protection from cardiac arrhythmia through ryanodine receptor-stabilizing protein calstabin2
    Xander H T Wehrens
    Department of Physiology and Cellular Biophysics, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA
    Science 304:292-6. 2004
    ..Thus, enhancing the binding of calstabin2 to RyR2 may be a therapeutic strategy for common ventricular arrhythmias...
  72. ncbi request reprint Ca2+/calmodulin-dependent protein kinase II phosphorylation regulates the cardiac ryanodine receptor
    Xander H T Wehrens
    Department of Physiology and Cellular Biophysics, Columbia University College of Physicians and Surgeons, 630 W 168th St, P and S 9 401, Box 65, New York, NY 10032, USA
    Circ Res 94:e61-70. 2004
    ..CaMKII-mediated phosphorylation of RyR2 may contribute to the enhanced contractility observed at higher heart rates. The full text of this article is available online at http://circres.ahajournals.org...
  73. ncbi request reprint Novel therapeutic approaches for heart failure by normalizing calcium cycling
    Xander H T Wehrens
    Department of Physiology and Cellular Biophysics, Center for Molecular Cardiology, Columbia University College of Physicians and Surgeons, 630W 168th Street, P and S 9 401, New York, New York 10032, USA
    Nat Rev Drug Discov 3:565-73. 2004
  74. ncbi request reprint Defective ryanodine receptor interdomain interactions may contribute to intracellular Ca2+ leak: a novel therapeutic target in heart failure
    Stephan E Lehnart
    Circulation 111:3342-6. 2005
  75. ncbi request reprint Sudden unexplained death caused by cardiac ryanodine receptor (RyR2) mutations
    Xander H T Wehrens
    Mayo Clin Proc 79:1367-71. 2004
  76. pmc The L-type calcium channel inhibitor diltiazem prevents cardiomyopathy in a mouse model
    Christopher Semsarian
    Department of Genetics, Howard Hughes Medical Institute and Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA
    J Clin Invest 109:1013-20. 2002
    ....
  77. ncbi request reprint Overexpression of beta2-adrenergic receptors cAMP-dependent protein kinase phosphorylates and modulates slow delayed rectifier potassium channels expressed in murine heart: evidence for receptor/channel co-localization
    Keith W Dilly
    Department of Pharmacology, Center for Molecular Cardiology, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA
    J Biol Chem 279:40778-87. 2004
    ..These data indicate intimate association of KCNQ1 and beta2-ARs and that beta2-AR signaling can modulate the function of IKs channels under conditions of increased beta2-AR expression, even in the absence of exogenous beta-AR agonist...
  78. ncbi request reprint Cardiac ryanodine receptor function and regulation in heart disease
    Stephan E Lehnart
    Center for Molecular Cardiology, Department of Physiology and Cellular Biophysics, Columbia University, College of Physicians and Surgeons, New York, NY 10032, USA
    Ann N Y Acad Sci 1015:144-59. 2004
    ..In conclusion, heart failure and exercise-induced sudden cardiac death have been linked to defects in RyR2-calstabin2 regulation, and this may represent a novel target for the prevention and treatment of these forms of heart disease...
  79. ncbi request reprint Phosphodiesterase 4D and heart failure: a cautionary tale
    Stephan E Lehnart
    Columbia University, Clyde and Helen Wu Center for Molecular Cardiology, Department of Physiology and Cellular Biophysics, New York, NY 10032, USA
    Expert Opin Ther Targets 10:677-88. 2006
    ..The authors review the contribution of PDE activity in the heart to contractile stress adaptation, the significance of altered cAMP signalling in heart failure, and the effects of PDE inhibition in heart disease...
  80. pmc Leaky Ca2+ release channel/ryanodine receptor 2 causes seizures and sudden cardiac death in mice
    Stephan E Lehnart
    Department of Physiology and Cellular Biophysics, Clyde and Helen Wu Center for Molecular Cardiology, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA
    J Clin Invest 118:2230-45. 2008
    ..Based on these data, we propose that CPVT is a combined neurocardiac disorder in which leaky RyR2 channels in the brain cause epilepsy, and the same leaky channels in the heart cause exercise-induced sudden cardiac death...
  81. pmc Remodeling of ryanodine receptor complex causes "leaky" channels: a molecular mechanism for decreased exercise capacity
    Andrew M Bellinger
    Clyde and Helen Wu Center for Molecular Cardiology, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA
    Proc Natl Acad Sci U S A 105:2198-202. 2008
    ..Taken together, these data suggest a possible mechanism by which Ca2+ leak via calstabin1-depleted RyR1 channels leads to defective Ca2+ signaling, muscle damage, and impaired exercise capacity...
  82. ncbi request reprint Sirolimus for the prevention of in-stent restenosis in a coronary artery
    Andrew R Marks
    Department of Physiology and Cellular Biophysics, Center for Molecular Cardiology, Columbia University College of Physicians and Surgeons, New York, USA
    N Engl J Med 349:1307-9. 2003
  83. ncbi request reprint Regulation of the type 1 inositol 1,4,5-trisphosphate receptor by phosphorylation at tyrosine 353
    Jie Cui
    Department of Physiology and Cellular Biophysics, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA
    J Biol Chem 279:16311-6. 2004
    ..Taken together, these data suggest that one function of tyrosine phosphorylation of IP3R1-Y353 is to enhance Ca2+ signaling in lymphocytes by increasing the sensitivity of IP3R1 to activation by low levels of IP3...

Research Grants38

  1. MOLECULAR BASIS OF HEART FAILURE
    Andrew Marks; Fiscal Year: 2006
    ..We propose to test the hypothesis that defective regulation of RyR1 due to PKA hyperphosphorylation and FKBP12 depletion contributes to impaired skeletal muscle function in heart failure. ..
  2. Regulation of cardiac ion channel function via allosteric modulators
    Andrew Marks; Fiscal Year: 2007
    ..The studies are significant because they may lead to a novel therapeutic approach based on allosteric modulation of RyR that can result in improved therapy for human cardiovascular diseases. ..
  3. CARDIAC AND SKELETAL MUSCLE CALCIUM RELEASE CHANNELS
    Andrew Marks; Fiscal Year: 2007
    ..6 to the channel resulting in improved cardiac function in heart failure, and prevention of cardiac arrhythmias. Thus, the proposed studies are highly relevant to human diseases including heart failure and cardiac arrhythmias. ..
  4. CARDIAC AND SKELETAL MUSCLE CALCIUM RELEASE CHANNELS
    Andrew Marks; Fiscal Year: 2006
    ..Pharmacologic manipulation, targeted at the regulation of FKBP12/12.6 binding to the channels and at phosphorylation/dephosphorylation of the channels, could ultimately provide novel approaches to treating these and other diseases. ..
  5. Multidisciplinary Training in Translational Cardiovascular Research
    Andrew Marks; Fiscal Year: 2007
    ....
  6. Molecular Basis of Sudden Cardiac Death
    Andrew Marks; Fiscal Year: 2007
    ..R. Marks, PI); 2) Animal Model Core. (J. D'Armiento, PI - This Core will generate and provide genetic animal models of ion channel diseases to each of the four projects). ..
  7. CARDIAC AND SKELETAL MUSCLE CALCIUM RELEASE CHANNELS
    Andrew Marks; Fiscal Year: 2009
    ..Thus, the proposed studies are highly relevant to human diseases including heart failure and cardiac arrhythmias. ..
  8. MOLECULAR BASIS OF HEART FAILURE
    Andrew Marks; Fiscal Year: 2009
    ..The proposed studies are significant because they will provide novel insights concerning the mechanisms of HF progression. ..
  9. MOLECULAR BASIS OF HEART FAILURE
    ANDREW ROBERT MARKS; Fiscal Year: 2010
    ..The proposed studies are significant because they will provide novel insights concerning the mechanisms of HF progression. ..
  10. MOLECULAR BASIS OF HEART FAILURE
    Andrew Marks; Fiscal Year: 2009
    ..The proposed studies are significant because they will provide novel insights concerning the mechanisms of HF progression. ..
  11. CARDIAC AND SKELETAL MUSCLE CALCIUM RELEASE CHANNELS
    Andrew Marks; Fiscal Year: 2000
    ..Elucidation of the structure/function relationships of RyR will help us understand the regulation of Ca release from sarcoplasmic reticulum. ..
  12. MOLECULAR BASIS OF HEART FAILURE
    Andrew Marks; Fiscal Year: 2002
    ....
  13. Intracellular calcium leak and muscle function
    ANDREW ROBERT MARKS; Fiscal Year: 2010
    ....