Dr. Cheng has broad background in cardiovascular physiology, pharmacology, and molecular biology with specific training and expertise in all the key aspects of the project. She is an established investigator in the field of CHF with primary focus on the modulation of left ventricular filling dynamics at rest and during exercise, the function significance of neurohormonal activation in CHF, adrenergic regulation in the setting of cardiomyopathies, as well as cardiac cellular [Ca2+]i regulation, signal transduction and energetics. She has extensive direct experience in the preparation and study of conscious instrumented animals (>25 years) performing sophisticated serial measurement of LV systolic and diastolic performance. In order to investigate the cellular and molecular mechanisms underlying our observations in conscious animals, she has developed the techniques to serially harvest myocytes before, during, and after the development of CHF from LV biopsies obtained from the same animals . As PI or co-Investigator on several previous university-, AHA- and NIH-funded grants, she has successfully completed several projects related functional significance of neurohormonal (including RAS and Beta-adrenergic activation before and as CHF progresses of several different animal models (including rat, mouse, dog and monkey). This proposal will directly address one of the most perplexing problems regarding the mechanism for the local formation of Ang II in cardiac tissue. The current grant application addresses the important problem of the impact of cardiovascular disease. Dr. Cheng has the expertise, training and motivation necessary to successfully carry out the proposed research project. In fact, Dr. Cheng’s knowledge and experience put her in a unique position to bring scientific insights to the proposed studies in this application.