Research in the Anderson laboratory focuses on cellular signaling and ionic mechanisms that cause heart failure, arrhythmias and sudden cardiac death, major public health problems worldwide. Our primary focus is on the multifunctional Ca2+ and calmodulin-dependent protein kinase II (CaMKII). Our laboratory identified CaMKII as an important pro-arrhythmic and pro-cardiomyopathic signal. These studies have 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.

 

CaMKII is activated by increased intracellular Ca2+ and oxidation. Diverse ‘upstream’ signals, including catecholamines and the renin-angiotensin-aldosterone pathway increase CaMKII activity. CaMKII is multifunctional because it has multiple ‘downstream’ targets. CaMKII catalyzed phosphorylation in myocardium appears to coordinate activity of many or most voltage-gated ion channels, Ca2+ homeostatic proteins and gene transcription events.

 

Under physiological conditions, CaMKII is important for excitation-contraction coupling and fight or flight increases in heart rate. However, myocardial CaMKII is excessively activated during disease conditions where it contributes to loss of intracellular Ca2+ homeostasis, membrane hyperexcitability, premature cell death, and hypertrophic and inflammatory transcription. These downstream targets appear to contribute coordinately and decisively to heart failure and arrhythmias. Recently, we have developed evidence that CaMKII also participates in asthma.

 

Our laboratory is funded by grants from the National Institutes of Health.

 

Our laboratory efforts are highly collaborative and involve undergraduate assistants, graduate students, postdoctoral fellows and faculty. Presently, our key areas of focus are:

1. Ion channel biology and arrhythmias

2. Cardiac pacemaker physiology and disease

3. Molecular physiology of CaMKII

4. Myocardial and mitochondrial metabolism

5. CaMKII and reactive oxygen species in asthma

 

 

 

Be sure to check out the Johns Hopkins School of Medicine's Cellular and Molecular Medicine program!

http://cmm.jhmi.edu/

© Copyright 2015 Mark E. Anderson Lab    |    Neil Wu