Dale Abel's Lab Page
Dale Abel's PubMed Literature Search
The Abel Research Lab originated at Harvard Medical School in Boston in 1995, and moved to the University of Utah in 2000. Our current research interests focus on elucidating the molecular mechanisms leading to cardiac dysfunction in diabetes and the regulation of myocardial growth and metabolism by insulin signaling.
Our laboratory objectives include:
1. Elucidating the molecular mechanisms that are responsible for cardiac failure in diabetes.
2. Elucidating the molecular signals that coordinate the mitochondrial and metabolic adaptations to cardiac growth.
3. Elucidating the mechanisms by which insulin and growth factor signaling regulate cardiac mitochondrial metabolism and the adaptation of the heart to stress.
4. Elucidating the role of mitochondrial dysfunction in the pathogenesis of insulin resistance, diabetes and its complications.
Our recent contributions have included an elucidation of the impact of oxidative stress on mitochondrial bioenergetics in obesity and diabetes and the identification of novel regulation of mitochondrial integrity in the heart by insulin signaling. Recent studies have focused on the contribution of hyperinsulinemia to cardiac pathology in diabetes and obesity, regulation of autophagy by insulin signaling and its role in diabetic cardiomyopathy and mechanisms linking insulin signaling and substrate excess to the regulation of mitochondrial dynamics in the heart. We have relied heavily on transgenic and gene-targeted mice (conventional as well as conditional and cell-type restricted KO mice) to address many of these questions.
We have also developed a comprehensive array of approaches such as measurement of mitochondrial energetics in subcellular organelles, determination of substrate flux in intact hearts, as well as cardiovascular phenotyping in intact mice. We are also using proteomics and gene arrays to identify novel insulin-regulated targets in the mitochondria and validating these results using cell-culture models and transcriptional assays.
1. Zhang QJ, Holland WL, Wilson L, Tanner JM, Kearns D, Cahoon JM, Dix P, Losee J, Duncan B, Gale D, Kowalski CA, Deeter N, Nichols A, Michole Deesing M, Arrant C, Ruan T, Boehme C, McCamey DR, Rou J, Ambal K, Narra KK, Summers SA, Abel ED, Symons JD (2012) Ceramide mediates vascular dysfunction in diet-induced obesity by PP2A-mediated dephosphorylation of the eNOS-Akt complex. Diabetes, in press
2. Bugger H, Riehle C, Jaishy B, Wende AR, Tuinei J, Chen D, Soto J, Pires KM, Boudina S, Theobald HA, Luptak I, Wayment B, Wang X, Sheldon E. Litwin SE, Weimer BC, Abel ED (2012) Genetic Loss of Insulin Receptors Worsens Cardiac Efficiency in Diabetes. J Mol Cell Cardiol, in press
3. Riehle C, Wende AR, Zaha VG, Pires KM, Wayment B, Olsen C, Bugger H, Buchanan J, Wang X, Moura AB, Doenst T, Medina-Gomez G, Litwin SE, Lelliott CJ, Vidal-Puig A, Abel ED (2011) PGC-1? Deficiency Accelerates the Transition to Heart Failure in Pressure Overload Hypertrophy. Circulation Research, 109:783-93
4. Abel ED, Doenst T (2011) Mitochondrial adaptations to physiological versus pathological cardiac hypertrophy. Cardiovascular Research, 90(2): 234-42
5. Sloan C, Tuinei J, Nemetz K, Frandsen J, Soto J, Wride N, Sempokuya T, Alegria L, Bugger H, Abel ED (2011) Central leptin signaling is required to normalize myocardial fatty acid oxidation rates in caloric-restricted ob/ob mouse hearts. Diabetes 60:1424-34
6. Son N-H, Yu S, Tuinei J, Arai K, Hamai H, Homma S, Shulman GI, Abel ED, Goldberg IJ (2010) PPAR-gamma-induced cardiolipotoxicity is ameliorated by PPAR-alpha deficiency despite greater fatty acid oxidation in mice. J Clin Invest 120:3443-54
7. Wende AR, Soto J, Olsen CD, Pires KM, Schell JC, Larrieu-Lahargue F, Litwin SE, Kakoki M, Takahashi N, Smithies O, Abel ED (2010) Loss of Bradykinin Signaling Does Not Accelerate the Development of Cardiac Dysfunction in Type 1 Diabetic Akita Mice. Endocrinology 151(8):3536-42
8. Shimizu I, Minamino T, Toko H, Okada S, Ikeda H, Yasuda N, Tateno K, Moriya J, Yokoyama M 1, Nojima A, Koh GY, Akazawa H, Shiojima I, Kahn CR, Abel ED, Komuro I (2010) Excessive cardiac insulin signaling exacerbates systolic dysfunction induced by pressure overload in rodents. J Clin Invest 120(5):1506-14
9. Zhang Y, Soto J, Park K, Viswanath G, Kuwada S, Abel ED, Wang L (2010) Nuclear receptor SHP, a death receptor that targets mitochondria, induces apoptosis and inhibits tumor growth. Molecular and Cellular Biology 30(6):1341-56
10. Bugger H, Chen D, Riehle C, Soto J, Theobald HA, Hu XX, Ganesan B, Weimer BC, Abel ED (2009) Tissue-Specific Remodeling of the Mitochondrial Proteome in Type 1 Diabetic Akita Mice. Diabetes, 58:1986-97
11. Symons JD, McMillin SL, Riehle C, Tanner J, Palionyte M, Hillas E, Jones D, Cooksey RC, Birnbaum MJ, McClain DA, Zhang Q-J, Gale D,Wilson LJ, Abel ED (2009) Contribution of insulin and Akt1 signaling to eNOS in the regulation of endothelial function and blood pressure. Circulation Research, 104:1085-1094