BLR&D Merit Review Research Career Scientist Award Application

Va San Diego Healthcare System, San Diego CA

Investigators

Linked publications & trials

Abstract

As the general population and veterans age, their hearts will undergo dramatic changes, reducing their capacity to work efficiently and increasing their susceptibility to injury. In addition, there are several 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. Multiple pathways of stress adaptation share an interconnected mediator that may be targeted therapeutically. The Patel Laboratory has focused on identifying novel and unique mediators that regulate many pathways and may be viable therapeutic endpoints for cardiovascular disease. The laboratory has a specific interest in caveolin 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 protect the heart are likely 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 be broadly applicable to other 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 explicitly been 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 several clinical problems. In 2004, Dr. Patel performed a simple experiment in which caveolae disruption showed that 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, define the role of caveolae in cardiac disease, and develop tools to target this therapeutically. The Patel Laboratory has also uncovered caveolin's specific, critical, and interconnected role in regulating cellular metabolism, which is being applied to more complex studies related to neuroscience, cancer, diabetes, aging, and renal biology. A licensed patent is being developed as a therapeutic for ALS, and clinical trials are expected to commence in the coming year. These advancements have positioned the laboratory as a leader in connecting structure to physiology in caveolin biology. Recent studies funded by a 5-year, $10M gift from the InnerScience Research Fund has launched a new area of mind-body research in the Patel Laboratory applying sophisticated biochemical, molecular, cell biology, and physiological measures to determine how the mind adapts that body to stressors during immersive meditations (IRB managed offsite by clinical group). The studies involve large cohorts (3000+ subjects, many veterans have participated) with multi-omic profiling. Dr. Patel leads a group of physicians and basic scientists to uncover this unique biology that has significant implications for veteran health.