F A C U L T Y P R O F I L E
ROSEN, MICHAEL R., M.D.
Developmental biology of the heart; cardiac-autonomic interactions; Mechanisms for cardiac arrhythmias and their prevention and control.
Office: Presbyterian Hospital | 7W 321
Dr. Michael R. Rosen is the Gustavus A. Pfeiffer Professor of Pharmacology, Professor of Pediatrics, and Director of the Center for Molecular Therapeutics at the College of Physicians and Surgeons of Columbia University in New York. He is also Adjunct Professor of Physiology and Biophysics at Stony Brook University and a member of Stony Brook’s Institute for Molecular Cardiology.
(1) Cardiac memory: Dr. Rosen and collaborators have identified the mechanisms whereby altered activation of the heart temporarily or permanently alters the expression of repolarization. Most importantly these studies help us understand the early molecular-biophysical and genetic changes that initiate remodeling in the setting of pacemaker therapy and specific arrhythmias. These studies are funded by the NHLBI;
(2) Gene and stem cell therapies. The most advanced aspect of this research is on biological pacemaking, in which use of adult human mesenchymal stem cells as a platform loaded with cardiac pacemaker genes is being tested as an alternative to electronic pacemaker therapy. The potential advantage of this approach is that it offers a more physiological pacemaker therapy than does electronic pacing. Dr. Rosen’s group also is working with gene and cell therapies of tachyarrhythmias, stem cells to effect myocardial replacement and repair and stem cells as platforms to introduce silencing RNA to various cell types as a potential anti-cancer therapy. These studies are funded by NHLBI and by NYSTEM.
1. Lau DH, Clausen C, Sosunov EA, Shlapakova IN, Anyukhovsky, Danilo P Jr, Rosen TS, Kelly CW, Duffy HS, Szabolcs MJ, Chen M, Robinson RB, Lu J, Kumari S, Cohen IS, Rosen MR. Epicardial border zone overexpression of skeletal muscle sodium channel, SkM1, normalizes activation, preserves conduction and suppresses ventricular arrhythmia: an in silico, in vivo, in vitro study. Circulation 2009;119:19-27.
2. Protas L, Dun W, Jia Z, Lu J, Bucchi A, Kumari S, Chen M, Cohen IS, Rosen MR, Entcheva E, Robinson RB. Expression of skeletal but not cardiac Na+ channel isoform preserves normal conduction in a depolarized cardiac syncytium. Cardiovas Res 2009;81:528-535.
3. Thomsen MB, Sosunov EA, Anyukhovsky EP, Özgen N, Boyden PA, Rosen MR. Deleting the accessory subunit KChIP2 results in loss of I(to,f) and increased I(K,slow) that maintains normal action potential configuration. Heart Rhythm 2009;6:370-7.
4. Thomsen MB, Wang C, Özgen N, Wang H-G, Rosen MR, Pitt GS. The accessory subunit KChIP2 modulates the cardiac L-type calcium current. Circ Res 2009; 104:1382-1389
5. Ozgen N, Guo J, Gertsberg Z, Danilo P, Rosen MR, Steinberg SF. Reactive oxygen species decrease cyclic AMP response element binding protein expression in cardiomyocytes via a protein kinase D1-dependent mechanism that does not require Ser133 phosphorylation. Mol Pharmacol 2009; 76:896-902.
6. Valiunas V, Kanaporis G, Valiuniene L, Gordon C, Wang H, Li L, Robinson RB, Rosen MR, Cohen IS, Brink PR. Coupling an HCN2 expressing cell to a myocyte creates a two cell pacing unit. J Physiol 2009; 587.21:5211-5226.
7. Reisner Y, Meiry G, Zeevi-Levin N, Barac DY, Reiter I, Abassi Z, Ziv N, Kostin S, Schaper J, Rosen MR, Binah O. Impulse conduction and gap junctional remodeling by endothelin-1 in cultured neonatal rat ventricular myocytes. J Cell Mol Med 2009;13:562-573.
8. Ozgen N, Lau DH, Shlapakova IN, Sherman W, Feinmark SJ, Danilo P Jr, Rosen MR.
Determinants of CREB degradation and KChIP2 gene transcription in cardiac memory. Heart Rhythm 2010;7:964-970.
9. Coronel R, Lau DH, Sosunov EA, Janse MJ, Danilo P Jr, Anyukhovsky EP, Wilms-Schopman FJG, Opthof T, Shlapakova IN, Ozgen N, Prestia K, Kryukova Y, Cohen IS, Robinson RB, Rosen MR. Cardiac expression of skeletal muscle sodium channels increases longitudinal conduction velocity in the canine 1-week myocardial infarction. Heart Rhythm 2010;7:1104-1110.
10. Shlapakova IN, Nearing BD, Lau DH, Boink GJJ, Danilo P Jr, Kryukova Y, Robinson RB, Cohen IS, Rosen MR, Verrier RL. Biological pacemakers in canines exhibit positive chronotropic response to emotional arousal. Heart Rhythm 2010;7:1835-40
11. Danon A, Zeevi-Levin N, Pinkovich DY, Michaeli T, Berkovich A, Flugelman M, Eldar YC, Rosen MR, Binah O. Hypoxia causes connexin43 internalization in neonatal rat ventricular myocytes. Gen. Physiol. Biophys 2010;29:222-233.
12. Anyukhovsky EP, Sosunov EA, Kryukova YN, Prestia K, Ozgen N, Rivaud M, Cohen IS, Robinson RB, Rosen MR. Expression of skeletal muscle sodium channel (Nav1.4) or connexin32 prevents reperfusion arrhythmias in murine heart. Cardiovasc Res: 2011;89:41-50.
13. Prestia KA, Sosunov EA, Anyukhovsky EP, Dolmatova E, Kelly CW, Brink PR, Robinson RB, Rosen MR, Duffy HS. Increased cell-cell coupling increases infarct size and does not decrease incidence of ventricular tachycardia in mice. Front Physiol. 2011; 31;2:1-7.