Faculty

Mahesh P. Gupta, PhD

Our scientists are forging new ground in heart failure research.  Led by Mahesh P. Gupta, PhD, our laboratory team is working on several exciting projects.  Dr. Gupta's primary research interest is seeking to understand the molecular basis of heart failure, particularly, the role played by the chromatin remodeling enzymes in muscle gene dys regulation and cell-death during failure. Heart failure is a pathological state in which the heart is unable to pump blood at a rate commensurate with the requirements of the metabolizing tissues. It is usually caused by a defect in myocardial contraction. Reduced myocardial contractile function may reflect a decrease in the number of viable myocytes, dysfunction of viable myocytes, or alterations to the intrinsic contractile activity of individual myocytes. At the molecular level, several abnormalities have been observed, including alterations in the expression of numerous genes that are central to the normal structure and function of the myocardium; however, the basic mechanism of heart failure is not yet fully understood. With recent advancements in cell biology, it has become clear that factors modifying chromatin structure, e.g. histone deacetylases, acetyltransferases and poly (ADP) polymerases play a fundamental role in this process. In addition to modifying chromatin structure, these enzymes also play a role outside the nucleus. We are trying to understand how these enzymes modify cytosolic proteins and regulate the cell-survivability and contractile function, in response to various physiologic and pathologic stresses.  For more information on the work that Dr. Gupta's team is performing, please visit http://roscoe.bsd.uchicago.edu/surgicalresearch/faculty/gupta/index.html. 

To view the most recent publication regarding the work being conducted in Dr. Gupta's lab, please click here.

The Akhter laboratory is currently investigating molecular mechanisms involved in the regulation of G protein-coupled receptor (GPCR) signaling in the heart as this relates to the development of cardiovascular disease processes including myocardial hypertrophy and the transition to heart failure.  Our research focuses on the role of a family of kinases which regulate GPCR signaling known as GPCR kinases (GRKs).  The GRKs appear to be important modulators of cardiac function in the normal and failing heart and manipulation of GRK activity may represent a novel strategy in the treatment of heart failure.  A primary area of investigation is in identifying mechanisms by which GRK activity is altered in the development of heart failure.  In addition to heart failure, we are also studying molecular mechanisms of donor heart dysfunction, as this represents a significant limitation to the field of heart transplantation where donor organs are in such short supply.  Our laboratory has been investigating the effects of brain death on cardiac adrenergic receptor signaling and GRK activity and how this can lead to impaired ventricular function.  We are also interested in particular inflammatory signaling pathways that appear to play a major role in donor heart dysfunction through the generation of nitric oxide.  This has also led to studying the effects of oxidative stress on adrenergic receptor signaling in cardiac myocytes and fibroblasts which can also play a significant role in ischemia-reperfusion injury as well as the development of heart failure.  Another program in the lab is the investigation of the effects of cardiopulmonary bypass during cardiac surgery on myocardial adrenergic receptor signaling and heart function, which is particularly important in optimizing myocardial protection strategies during heart surgery and improving outcomes in higher risk patient populations.