This second revision of 5 year clinical scientist training proposal describes the program to provide new scientific knowledge and facilitate the transition to an independent cardiovascular research career as a Molecular Cardiologist. The applicant has completed clinical training and is board certified in both Internal Medicine and Cardiology. The applicant has engaged in basic science and clinical physiology research and will utilize the expertise and resources within multiple departments at the University of Colorado to gain proficiency in a new area of scientific evaluation. The training program will focus on the biochemistry and molecular biology of sex differences in cardiac disease. Dr. Leslie Leinwand will mentor the principal investigator's scientific development. She is recognized as a leader in the molecular biology of cardiomyopathies. The program has enlisted several expert clinical molecular cardiologists and a molecular endocrinologist as co-Sponsors. The advisory committee is composed of faculty who are nationally and internationally renowned in their particular field. Over the past several decades a sex-dependent difference in cardiac phenotype has been described in clinical hypertrophic disease, however, the mechanisms behind this difference remain elusive. Recent work by the applicant has discovered sex dependent differences in cardiac functional phenotype in an animal model of hypertrophic cardiomyopathy which can be altered by dietary modification. This model will serve to begin the dissection of molecular and cellular mechanisms behind this disease.
The specific aims propose to identify the molecular pathways involved in this sex dependent difference and will evaluate sex hormones and diet as interventions which modify the pathophysiologic phenotype. The investigator proposes to identify the mechanism by which altering the diet prevents the development of a sex-dependent dilated cardiomyopathic phenotype. In addition, the investigator proposes to determine the contribution of sex hormones to the sex-dependent differences in hypertrophic cardiac disease. The Department of Cardiology at the University of Colorado provides the ideal location to train basic research clinician-scientists through the integration of interdepartmental and intercampus expertise. The department's flexibility provides investigators with the support necessary to utilize all available resources to tailor the research program toward a unique focus necessary to launch an independent research career.
|Stauffer, Brian L; Dockstader, Karen; Russell, Gloria et al. (2015) Transgenic over-expression of YY1 induces pathologic cardiac hypertrophy in a sex-specific manner. Biochem Biophys Res Commun 462:131-7|
|Miyamoto, Shelley D; Stauffer, Brian L; Nakano, Stephanie et al. (2014) Beta-adrenergic adaptation in paediatric idiopathic dilated cardiomyopathy. Eur Heart J 35:33-41|
|Sucharov, Carmen C; Hijmans, Jamie G; Sobus, Rebecca D et al. (2013) *-Adrenergic receptor antagonism in mice: a model for pediatric heart disease. J Appl Physiol (1985) 115:979-87|
|Haines, Christopher D; Harvey, Pamela A; Luczak, Elizabeth D et al. (2012) Estrogenic compounds are not always cardioprotective and can be lethal in males with genetic heart disease. Endocrinology 153:4470-9|
|Stauffer, Brian L; Sobus, Rebecca D; Sucharov, Carmen C (2011) Sex differences in cardiomyocyte connexin43 expression. J Cardiovasc Pharmacol 58:32-9|
|Stauffer, Brian L; Westby, Christian M; Greiner, Jared J et al. (2010) Sex differences in endothelin-1-mediated vasoconstrictor tone in middle-aged and older adults. Am J Physiol Regul Integr Comp Physiol 298:R261-5|
|Mestek, Michael L; Weil, Brian R; Greiner, Jared J et al. (2010) Osteopenia and endothelin-1-mediated vasconstrictor tone in postmenopausal women. Bone 47:542-5|
|Stauffer, Brian L; Maceneaney, Owen J; Kushner, Erich J et al. (2008) Gender and Endothelial Progenitor Cell Number in Middle-Aged Adults. Artery Res 2:156-160|