The work in the laboratory of Dr. Djamel Lebeche focuses on targeting molecular and cellular pathways to improve contractile function and survival in failing cardiac myocytes. We are particularly interested in the impact of diabetes on the heart and the ensuing diabetes-induced left ventricular dysfunction. The genetic and cellular mechanisms underlying the pathophysiology of diabetic cardiomyopathy are not well understood. We are using gene therapy approaches to target specific abnormalities that have been identified in failing hearts at the cellular level. Animal models of type I and type II diabetes are utilized in addition to primary cultures of human and adult rat ventricular myocytes.

Specifically we are:

1. Targeting Insulin Signaling Pathways in Diabetic Cardiomyopathy: we are testing the hypothesis that restoration of calcium homeostasis as well as metabolic intervention will not only attenuate the contractile defect but also improve long-term survival. Understanding the role of calcium regulation and myocardial energetic signaling in cardiomyocyte dysfunction and developing approaches to local modulation of these pathways through somatic gene transfer, may provide novel therapeutic approaches for the management of diabetes-induced cardiomyopathy.
2. Profiling the Proteomics and Genomics of Diabetes-induced Cardiac Dysfunction: Our aim is to investigate the changes in gene and protein expression profiles accompanying diabetic cardiomyopathy and to identify genes and proteins whose expression is altered in response to diabetes and to acute in vivo insulin stimulation. Proteomic and genomic profiling obtained will provide an effective way to assess global effects and may provide important clues as to the critical pathways that are altered by diabetes and following insulin treatment.

Dr. Lebeche, currently an Assistant Professor of Medicine, was recruited to the Cardiovascular Research Center from Massachusetts General Hospital where he was an instructor of Medicine at Harvard Medical School. Dr. Lebeche's research is focused on targeting molecular and cellular pathways to improve contractile function and survival in failing cardiac myocytes with particular interested in diabetes-induced left ventricular dysfunction. Using gene therapy approaches to target specific abnormalities, the genetic and cellular mechanisms underlying the pathophysiology of diabetic cardiomyopathy are being investigated in his laboratory. In addition, proteomic and genomic approaches are used to identify new targets in heart failure.