OVERALL PROJECT SUMMARY/ABSTRACT Cardiovascular (CV), renal and metabolic diseases are inextricably linked and are the leading causes of mortality and morbidity in the U.S., especially in Mississippi which has the highest prevalence in the nation of these diseases. Cardiorenal and metabolic disorders usually cluster together and are highly interdependent. Obesity and associated metabolic disorders, such as diabetes mellitus, are major causes of CV and renal disease. Abnormal kidney function is an important cause as well as a consequence of hypertension, a key risk factor for CV diseases such as coronary artery disease and stroke. Understanding the complex relationships among CV, renal, and metabolic disorders and developing new therapeutic approaches requires a paradigm shift in research that incorporates multidisciplinary integrated approaches, combining the efforts of basic, clinical and population scientists. A major objective of this Phase 3 COBRE proposal is to amplify the success of Phases 1 and 2 in developing a leading Cardiorenal and Metabolic Diseases Research Center (CMDRC) that brings together a multidisciplinary group of basic, clinical and population scientists working on a common synergistic theme, and to facilitate their collaborations. The specific aims for Phase 3 are: 1) To further develop CMDRC infrastructure, a well-organized highly productive Pilot Projects Program (PPP), and sustainable research core facilities that foster excellence in basic, clinical, and population research in cardiorenal and metabolic diseases and increased competitiveness of CMDRC investigators for independent funding from NIH and other national biomedical research programs; 2) To enhance CMDRC mentoring and education programs that provide support for PPP investigators as well as other promising researchers so that they can become productive, independent investigators who are also effective collaborators on multidisciplinary research teams; 3) To amplify our pipeline of diverse postdoctoral fellows and students trained in cutting-edge cardiorenal and metabolic diseases research so they become the next generation of researchers in this field; major emphasis is placed on recruiting and mentoring underrepresented minority investigators through partnerships with local institutions and by leveraging training programs at UMMC; 4) To enhance collaborations and interactions among established and junior investigators from multiple disciplines in cardiorenal and metabolic diseases at UMMC, other IDeA supported programs, and external partners. These interactions will leverage resources provided by UMMC and other IDeA programs; 5) To further expand the number of highly productive, extramurally funded cardiorenal and metabolic disease researchers at UMMC by leveraging institutional resources to recruit additional new faculty with expertise in clinical and translational research, and in areas where there are gaps in CMDCR expertise. The CMDRC has been a major driver for marked expansion of cardiorenal and metabolic diseases research in Mississippi. Phase 3 support will amplify and ensure sustainability of our efforts to develop a highly productive CMDRC dedicated to improving lives through research, discovery, and innovation.

OVERALL NARRATIVE Cardiovascular, kidney and metabolic diseases are the leading causes of mortality and morbidity in the United States, especially in Mississippi which has the highest prevalence in the nation of these diseases. This is a critical area for research development in Mississippi in view of the emerging opportunities to develop a comprehensive, multidisciplinary research center at UMMC that focuses on these major causes of mortality and morbidity. This proposal represents a plan for continued development, via Phase 3 COBRE funding, of a unique, Cardiorenal and Metabolic Diseases Research Center (CMDRC) that is dedicated to improving lives through research, discovery, innovation, and translation to prevent and reduce death and disability from cardiorenal and metabolic diseases.