Novel signaling pathways in metabolic disease associated cardiac remodeling
Our laboratory studies the interaction between acquired heart diseases and cardiac remodeling. One focus of the lab is on how kinases and other signaling pathways that are altered in metabolic diseases such as diabetes and insulin resistance (notably AMP-kinase and SGK-1) alter ion channel function, and how that correlates with myocardial energetics. A second project assesses the role of a novel mTORC regulator ddit4L in autophagy, cell death and energetics in response to metabolic stressors. A final project characterizes the role of plasma extracellular RNAs (ex-RNA) as a novel paracrine signaling mechanism in cardiac diseases including cardiometabolic diseases such as insulin resistance and metabolic syndrome. We use cell culture, patch clamping, transgenic and other mice models as well as novel imaging tools to answer these questions. We then try and correlate these findings in human subjects using retrospective and prospective cohort analyses.
1. Cook SA, Carver AV, Mongillo M, Khan MT, Leccisotti L, Strickland N, Matsui T, Das S, Rosenzweig A, Punjabi P and Camici, PG. (2010) Abnormal Myocardial Insulin Signaling in TypeII Diabetes and Left Ventricular Dysfunction. European Heart Journal 31(1): 100-111. PMCID: PMC2800920
2. Rosenberg MA, Das S*, Quintero P, Knight A, Sosnovik DE, Ellinor PT and Rosenzweig A*. (2012). A novel transgenic mouse model of cardiac hypertrophy and atrial fibrillation. J. Atrial Fibrillation 2 (9): 1-15-2012. (*: co-corresponding author). PMCID: PMC3521534
3. Shah RV, Altman RK, Park MY, Zilinski J, Leyton-Mange J, Orencole M, Picard MH, Barrett CD, Heist EK, Upadhyay G, Das RK, Singh JP, and Das S. (2012). Usefulness of Hemoglobin A1c to Predict Outcome After Cardiac Resynchronization Therapy in Patients with Diabetes Mellitus and Heart Failure. American Journal of Cardiology 110(5): 683-8. PMCID: PMC3483789
4. Das S, Aiba T, Rosenberg M, Hessler K, Xiao C, Quintero P, Ottaviano FG, Knight AC, Graham EL, Bostrum P, Morissette MR, del Monte F, Begley MJ, Cantley LC, Ellinor PT, Tomaselli GF and Rosenzweig A. (2012). Pathological Role of Serum- and Glucocorticoid-Regulated Kinase 1 in Adverse Ventricular Remodeling. Circulation 126 (18): 2208-19. PMCID: PMC3484211.
5. Graham EL, Balla C, Franchino H, Melman Y, delMonte F* and Das S* (2013). Isolation, Culture, and Functional Characterization of Adult Mouse Cardiomyocytes. J. Vis Exp 24 (79). PMID 24084584. PMCID: in progress
6. Otavio RC, Shah RV, Mitchell R, Neilan TG, Moreno H, Simonson B, Kwong R, Rosenzweig A, Das S and Jerosch-Herold M (2013). Quantification of Cardiomyocyte Hypertrophy by Cardiac Magnetic Resonance: Implications on Early Cardiac Remodeling. Circulation 128 (11): 1225-33. PMID 23912910, PMCID: in progress. (TG)
7. Mahida S, Mills R, Tucker NR, Simonson B, Macri V, Lemoine MD, Das S, Milan DJ and Ellinor PT (2014). Overexpression of KCNN3 Results in Sudden Cardiac Death. Cardiovascular Research 101(2): 326-34. PMID: 24296650, PMCID:PMC3896252 [Available on 2015/2/1]