The goal of this application is to provide protected time for Jonathan Williams, M.D. to become a successful independent, patient-oriented research investigator in the field of hormonal mechanisms affecting cardiovascular function in type II diabetes mellitus (DM). Brigham and Women's Hospital and its top-notch General Clinical Research Center will provide an ideal setting in which to peform the studies proposed and a unique opportunity to train a truly interdisciplinary researcher. Critical to obtaining this goal is his ability to acquire three important tools: 1) detailed didactic training in his field of investigation, 2) discipline and organizational expertise and 3) the practical skills necessary to conduct patient-oriented research. To accomplish this, he will participate in advanced didactic courses and conduct a mentored patient-oriented research project under the mentorship of Dr. Paul Conlin. Dr. Williams' proposal expands upon the findings of the Dietary Approaches to Stop Hypertension (DASH) studies, which showed that dietary intake could significantly lower blood pressure. The DASH diet is particularly effective in individuals with hypertension, yet we do not know how the DASH diet works and, beyond its blood pressure lowering effects, we do not know whether the DASH diet might more broadly affect structural and functional abnormalities in the cardiovasculature that frequently accompany patients with DM. Our preliminary data strongly support the possibility that the DASH diet interrupts the renin-angiotensin system in cardiovascular tissues. These and other data raise the intriguing possibility that the DASH diet produces effects that mimic angiotensin converting enzyme (ACE) inhibition. Such effects would offer clear benefits to individuals with the cardiovascular risk factors inherent in DM. In this proposal, Dr. Williams will introduce techniques and skills acquired during his research training to answer the question how the DASH diet affects cardiovascular function in DM. This award will provide the protected time and resources to (1) solidify his didactic training, (2) design, conduct, and complete a patient-oriented research project, and (3) continue to be mentored by leaders in his field of study. It will provide a clear pathway for him to establish an independent patient- oriented research career in cardiovascular endocrinology. ? ? ?
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