As the general population and veterans age, their hearts will undergo dramatic changes that will reduce their capacity to work efficiently and increase their susceptibility to injury. In addition, there are a number of co- morbidities such as diabetes that ensue with age that will further impact the heart and its adaptation to stress. Interventions that help to protect the heart from injury are likely to be useful in patients at high risk for cardiovascular events. Along with the general population, as veterans age, there will be an increasing burden of healthcare associated with age that lead to cardiovascular dysfunction. There are a number of molecular targets that may be critical in protection of the myocardium to stress but a unifying factor has been elusive, and thus a pharmacologic target not well defined. It is possible that multiple pathways of stress adaptation share an interconnected mediator that may be targeted therapeutically. The Patel Laboratory has been focused on identifying novel and unique mediators that regulate a multitude of pathways and may therefore be viable therapeutic endpoints for cardiovascular disease. The laboratory has a specific interest in caveolin and A- kinase interacting protein. There is clear clinical implication and need for interventions that limit the severity of injury that occurs to the myocardium, as this is a major risk factor to morbidity and mortality. Interventions that help to protect the heart are likely to be useful in many patients. Also, the basic nature of the studies underway in the Patel Laboratory to understand the fundamental physiology of the cell may also be broadly applicable to others organs and disease systems including but not limited to cancer biology, neurodegeneration, nephrology, urology, muscle physiology, pulmonary diseases, and the biology of aging. The Patel Laboratory has been specifically interested in assessing the impact of caveolae, membrane microdomains enriched in lipids and the structural protein caveolin, on cardiac physiology and pathophysiology for over a decade. Ongoing and collaborative studies with other national and international institutions has resulted in expansion in multiple organ systems and the potential to translate basic findings to a number of clinical problems. In 2004 Dr. Patel performed a very simple experiment where caveolae disruption showed that both ischemia- and opioid-induced cardiac protection was lost. This single experiment launched further inquiry into defining the role of caveolae in the heart especially as it relates to disease pathology;; this was the initial research funded by a Scientist Development Grant from the American Heart Association. The laboratory has sustained and expanded this focus over the years to uncover fundamental biology to define the role of caveolae in cardiac disease and develop tools to target this therapeutically. The Patel Laboratory has also uncovered a specific, critical, and...