EJ Anderson Lab
Area #1: Cross-talk between Monoamines and Nutrient Metabolism in the Heart
Myocardial Redox Status, Catecholamine Metabolism and Postoperative Arrhythmia (R01HL122863)
At the basic level, we are interested in understanding the extent to which monoamine oxidase (MAO), the mitochondrial enzyme responsible for metabolism of catecholamines (e.g., norepinephrine, dopamine, 5-HT) affects metabolism and in particular, mitochondrial efficiency (ATP/O) in the heart. Catecholamine metabolism by MAO generates H2O2 and reactive catechol-aldehydes, and we are interested in understanding how this reaction disrupts cardiomyocytes energetics, and the mechanisms by which it does this. We are also studying catecholamine metabolism in fibroblasts, and looking at the potential role of MAO in fibroblast proliferation and collagen production. It has recently been shown that MAO is one of the causal factors in diabetic cardiomyopathy, and heart failure, we have projects ongoing in diabetic rodent models to investigate these questions in a disease context.
To do this we use mitochondrial preparations from rodent and human heart (permeabilized fibers and isolated organelles), and cardiomyocyte cell culture.
Using the blood and atrial tissue samples from patients undergoing heart surgery, our goal is to identify prognostic biomarkers to determine risk of heart failure and arrhythmia in patients using genomic, proteomic and standard biochemical techniques. Currently, we have a single-institution trial ongoing, with plans to expand to multiple heart surgery centers in near future. The goal is to build risk models of postoperative A-fib and heart failure by measuring enzyme activity in atrial appendage tissue (time of surgery), or preoperative blood. We have also initiated targeted genomic & metabolomic analysis of these samples are also used to examine if novel biomarkers can be identified. From a pharmaceutical perspective, we anticipate that with these risk models we will be able to specifically identify individuals who may benefit from a prophylactic, or preventative therapy, if we know that they have a high risk for developing A-fib or heart failure, for example. This is an example of ‘personalized medicine,’ a new era in medical care.
Check out Dr. Anderson's interview with the local news about the clinical implications of the research being conducted in the lab! https://www.youtube.com/watch?v=6IYky1PkEmU&feature=youtu.be
Here's an article written by ECU about the research: http://www.ecu.edu/news/afibresearch.cfm