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Molecular Biology Section

Toren Finkel, MD, PhD, Principal Investigator

Levels of intracellular hydrogen peroxide as assesed by DCF fluorescence in vascular smooth muscle cells

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The current focus of the laboratory is to try to understand the role of reactive oxygen species (ROS) as intracellular signaling molecules. Oxygen radicals have been implicated in a number of conditions ranging from aging to atherosclerosis. Relatively little is known regarding how ROS like superoxide and hydrogen peroxide are regulated in cells and what specific aspects of cellular activity might be influenced by physiological and pathophysiological levels of these molecules. We are attempting to use a molecular biological approach to address these issues. It is our hope that we can gain a broader and more complete understanding of how cellular ROS are regulated. In addition, we are attempting to identify the direct molecular targets of cellular oxidants. Finally, we are hopeful that this molecular understanding will lead to new insights into disease states in which oxidant stress plays a role and help in the design of new therapeutic agents. 


Other Investigators:

Michael N Sack

Investigator in translational heart failure research

The current focus of the laboratory is to understand the regulatory control of mitochondrial function in the development of and in the prevention of cardiovascular diseases such as heart failure and ischemic heart disease. Current data suggest that mitochondria may play a central role in the augmenting cell survival programs in the heart. We are exploring the molecular regulatory control of mitochondrial function to enhance our understanding of the genomic control of mitochondrial function in response to numerous disease states (cardiac ischemia, diabetic associated cardiomyopathy). The long term goal will be to identify regulatory targets that could be exploited to enhance mitochondrial function in patients with heart failure and ischemic heart disease. In addition, the laboratory has an ongoing translational focus where evaluate novel mitochondrial modulatory therapies in the management of heart failure.

Selected Publications

Dr. Paul M Hwang

Investigator in cardiovascular genetic research

We are focusing on discovering some of the genetic determinants of atherosclerosis that may lead to new diagnostic markers, therapeutic targets and insights into pathogenesis. Our research involves using unbiased global genetic screens such as Serial Analysis of Gene Expression (SAGE) on patient samples and various model systems. Leading candidate genes are examined using molecular techniques in experimental models that include transgenic mice and somatic cell gene knockouts. In addition, we have previously shown that the p53 tumor suppressor gene can potently generate reactive oxidants in the mitochondria. We are now investigating novel mechanisms of mitochondrial regulation by the nucleus that may be important for energy and oxidant generation with direct consequences on cardiovascular function.

Selected Publications



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Department of Health and Human Services National Institutes of Health National Heart, Lung, and Blood Institute