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Mark E. Anderson, MD, PhD

M_anderson
Department Affiliations Medicine, Molecular Physiology and Biophysics
Rank Professor
Office Phone 410-955-6642
Lab Phone
Fax
Email Mark.Anderson@jhmi.edu
SOM Address 472 Rangos
Website

Anderson Lab

Students

Research Interests

Dr. Anderson has primarily focused his research on the role of the enzyme CaMKII (Ca2+/calmodulin dependent kinase II) in heart failure and cardiac arrhythmias, a cause of sudden cardiac death.

His laboratory identified CaMKII as an important pro-arrhythmic and pro-cardiomyopathic signal. His work has provided proof of concept evidence motivating active efforts in biotech and the pharmaceutical industry to develop therapeutic CaMKII inhibitory drugs to treat heart failure and arrhythmias. His group discovered that CaMKII is activated by oxidation and excessive CaMKII activity participates in cellular injury in response to diverse ‘upstream’ signals, including the renin-angiotensin-aldosterone pathway and endotoxin by oxidative activation. CaMKII is multifunctional because it has multiple ‘downstream’ targets. CaMKII catalyzed phosphorylation of diverse proteins in myocardium appears to coordinate activity of many or most voltage-gated ion channels, Ca2+ homeostatic proteins and gene transcription. Under physiological conditions, CaMKII is important for excitation-contraction coupling and fight or flight heart rate increases. However, myocardial CaMKII is excessively activated during disease conditions where it contributes to loss of intracellular Ca2+ homeostasis, membrane hyper-excitability, premature cell death, and hypertrophic and inflammatory transcription. These downstream targets appear to contribute coordinately and decisively to heart failure and arrhythmias. Recently, his group has developed evidence that CaMKII also participates in asthma and diabetes.

Publications

Research Profile

  • Zhang R, Khoo MS, Wu Y, Yang Y, Grueter CE, Ni G, Price EE Jr, Thiel W, Guatimosim S, Song LS, Madu EC, Shah AN, Vishnivetskaya TA, Atkinson JB, Gurevich VV, Salama G, Lederer WJ, Colbran RJ, Anderson ME. Calmodulin kinase II inhibition protects against structural heart disease. Nat Med 2005 Apr; 11(4):409-17. PMID 15793582 Commentary in Nat Med, 2005 Apr; 11(4): 379-80 PMID 15812516
  • Erickson JR, Joiner ML, Guan X, Kutschke WJ, Yang J, Oddis CV, Bartlett RK, Lowe JS, O’Donnell SE, Aykin-Burns N, Zimmerman MC, Zimmerman K, Ham AJ, Weiss RM, Spitz DR, Shea MA, Colbran RJ, Mohler PJ, Anderson ME. A dynamic pathway for calcium-independent activation of CaMKII by methionine oxidation. Cell 2008 May 2; 133(3):462-74. PMCID: PMC2435269. Published with accompanying editorial in Cell 2008 May 2; 133(3):397-9. PMCID: PMC2655315. Commentaries in Nat Med, 2008 May 2; 14(5):612 and Science Signaling, 2008, 1:ec161.
  • He BJ, Joiner ML, Singh MV, Luczak ED, Swaminathan PD, Koval OM, Kutschke W, Allamargot C, Yang J, Guan X, Zimmerman K, Grumbach IM, Weiss RM, Spitz DR, Sigmund CD, Blankesteijn WM, Heymans S, Mohler PJ, Anderson ME. Oxidation of CaMKII determines cardiotoxic effects of aldosterone. Nat Med 2011 Nov 13; 17(12): 1610-9. PMCID PMC3332099.
  • Luo M, Guan X, Luczak ED, Di L, Kutschke W, Gao Z, Yang J, Glynn P , Sossalla S, Swaminathan PD, Weiss RM, Yang B, Rokita AG,5, Maier LS, Efimov I, Hund TJ, Anderson ME. Diabetes increases mortality after myocardial infarction by oxidizing CaMKII. J Clin Invest 2013 Mar 1; 123(3):1262-74. PMCID: PMC3673230.
  • Sanders PN, Koval OM, Jaffer OA, Prasad AM, Businga TR, Scott JA, Hayden PJ, Luczak ED, Dickey DD, Allamargot C, Olivier AK, Meyerholz DK, Robison AJ, Winder DG, Blackwell TS, Dworski R, Sammut D, Wagner BA, Buettner GR, Pope MR, Miller FJ, Dibbern ME, Haitchi HM, Mohler PJ, Howarth PH, Zabner J, Kline JN, Grumbach IM, Anderson ME. CaMKII is Essential for the Proasthmatic Effects of Oxidation. Sci Trans Med 2013 Jul 24; 5(195):195 ra97. PMCID: PMC4331168. Commentary in JAMA. 310(9):894. Selected as a recommended citation by the Faculty of 1000 Biology.
  • Wu Y, Rasmussen TP, Koval OM, Joiner MA, Hall DD, Chen B, Luczak ED, Wang Q, Rokita AG, Wehrens XHT, Song L, Anderson ME. The mitochondrial uniporter controls fight or flight heart rate increases. Nature Communications 2015 Jan 20;6:6081. PMID 25603276.