Shahab Akhter, MD

Assistant Professor
Cardiac and Thoracic Surgery
Department of Surgery
University of Chicago
5841 S. Maryland Ave. MC 5035
Chicago, IL 60637
Phone: 773-702-2500
Email:

 

 

Akhter Group Links

• Clinical Interests
• Complete Bibliography

Research Interests

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.

 

Selected Publications

Rockman HA, Choi DJ, Rahman NU, Akhter SA, Lefkowitz RJ, Koch WJ. Receptor Specific In Vivo Desensitization by the G Protein-Coupled Receptor Kinase-5 in Transgenic Mice. (1996) Proc. Natl. Acad. Sci. U.S.A. 93(18):9954-9959 (PubMed)

Akhter SA, Milano CA, Shotwell KF, Cho MC, Rockman HA, Lefkowitz RJ, Koch WJ. Transgenic Mice with Cardiac-Specific Overexpression of a1B-Adrenergic Receptors; In Vivo a1-Mediated Regulation of b-Adrenergic Signaling. (1997) J. Biol. Chem. 272(34):21253-21259 (PubMed)

Akhter SA, Skaer CA, Kypson AP, McDonald PH, Peppel KC, Glower DD, Lefkowitz RJ, Koch WJ. Restoration of b-Adrenergic Signaling in Failing Cardiac Ventricular Myocytes Via Adenoviral-Mediated Gene Transfer. (1997) Proc. Natl. Acad. Sci. U.S.A. 94(22):12100-12105 (PubMed)

Chen EP, Bittner HB, Akhter SA, Koch WJ, Davis RD. Myocardial Recovery After Ischemia and Reperfusion Injury is Significantly Impaired in Hearts with Transgenic Overexpression of b-Adrenergic Receptor Kinase. (1998) Circulation 98:II-249-II-254 (PubMed)

Kypson AP, Peppel K, Akhter SA, Lilly RE, Glower DD, Lefkowitz RJ, Koch WJ. Ex Vivo Adenovirus-Mediated Gene Transfer to the Adult Rat Heart. (1998) J Thorac Cardiovasc Surg 115(3):623-630 (PubMed)

Koch WJ, Lefkowitz RJ, Milano CA, Akhter SA, Rockman HA. Myocardial Overexpression of Adrenergic Receptors and Receptor Kinases. (1998) Adv. Pharm. 42:502-506 (PubMed)

Rockman HA, Choi DJ, Akhter SA, Jaber M, Giros B, Lefkowitz RJ, Caron MG, Koch WJ. Control of Myocardial Contractile Function by the Level of b-Adrenergic Receptor Kinase 1 in Gene Targeted Mice. (1998) J. Biol. Chem. 273(29):18180-18184 (PubMed)

Akhter SA and Koch WJ. Myocardial Gene Transfer of b-Adrenergic Signaling Components as a Potential Therapy for Heart Failure. (1998) Congestive Heart Failure (September/October)

Akhter SA, Luttrell LM, Rockman HA, Iaccarino G, Lefkowitz RJ, Koch WJ. Targeting the Receptor-Gq Interface to Inhibit in Vivo Pressure Overload Myocardial Hypertrophy. (1998) Science 280(5363):574-577 (PubMed)

Chen EP, Akhter SA, Bittner HB, Davis RD, Koch WJ, Van Trigt P. Molecular and Functional Mechanisms of Right Ventricular Adaptation in Chronic Pulmonary Hypertension. (1999) Ann. Thor. Surg. 67:1053-1058 (PubMed)

Xiao R-P, Avdonin P, Zhou Y-Y, Cheng H, Akhter SA, Eschenhagen T, Lefkowitz RJ, Koch WJ, Lakatta EG. Coupling of the b2-Adrenoceptor to Gi Proteins and Its Physiological Relevance in Murine Cardiac Myocytes. (1999) Circ Res. 84:43-52 (PubMed)

Kypson AP, Hendrickson SC, Akhter SA, Wilson K, McDonald PH, Lilly RE, Dolber PC, Glower DD, Lefkowitz RJ, Koch WJ. Adenoviral-Mediated Gene Transfer of the b2-Adrenergic Receptor to Donor Hearts Enhances Cardiac Function. (1999) Gene Therapy 6(7):1298-1304 (PubMed)

Akhter SA, Eckhart AD, Rockman HA, Shotwell KF, Lefkowitz RJ, Koch WJ. In Vivo Inhibition of Elevated Myocardial b-Adrenergic Receptor Kinase Activity in Hybrid Transgenic Mice Restores Normal b-Adrenergic Signaling and Function. (1999) Circulation 100(6):648-653 (PubMed)

Chen EP, Bittner HB, Akhter SA, Koch WJ, Davis RD. Myocardial Function in Hearts With Transgenic Overexpression of the G Protein-Coupled Receptor Kinase 5. (2001) Ann. Thor. Surg. 71(4):1320-1324 (PubMed)

Schaeffer MW, Buell JF, Gupta M, Conway GD, Akhter SA, Wagoner LE. Strongyloides Hyperinfection Syndrome Following Heart Transplantation: Case Report and Review of the Literature. (2004) J Heart Lung Transplant 23(7):905-11 (PubMed)

Akhter SA, McGinty J, Konys JJ, Giesting RM, Merrill WH, Wagoner LE. Recurrent Primary Cardiac Malignant Fibrous Histiocytoma Following Orthotopic Heart Transplantation. (2004) J Heart Lung Transplant 23:1447-50 (PubMed)

Merrill WH, Akhter SA, Wolf RK, Schneeberger EW, Flege JB. Simplified Treatment of Postoperative Mediastinitis. (2004) Ann Thor Surg 78(2):608-12 (PubMed)

Petrashevskaya NN, Bodi I, Koch SE, Akhter SA, Schwartz A. Effects of a1-Adrenergic Stimulation on Normal and Hypertrophied Myocardium. Relation to Caveolin-3 Expression. (2004) Cardiovasc Res. 63(3):561-72 (PubMed)

Lyons JM, Pearl JM, McLean KM, Akhter SA, Wagner CJ, Pandalai PK, Duffy JY. Glucocorticoid Administration Reduces Cardiac Dysfunction After Brain Death. (2005) J Heart Lung Transplant 24(12):2249-54 (PubMed)

Bodi I, Mikala G, Koch SE, Akhter SA, Schwartz A. The L-Type Calcium Channel in the Heart: The Beat Goes On (Review). (2005) J Clin Invest 115:3306-3317 (PubMed)

Pandalai PK, Lyons JM, Duffy JY, McLean KM, Wagner CJ, Pearl JM, Merrill WH, Akhter SA. Role of the b-Adrenergic Receptor Kinase in Myocardial Dysfunction After Brain Death. (2005) J Thorac Cardiovasc Surg 130:1183-9 (PubMed)

Akhter SA, D’Souza KM, Petrashevskaya NN, Mialet-Perez J, Liggett SB. Myocardial b1-Adrenergic Receptor Polymorphisms Affect Functional Recovery Following Ischemic Injury. (2006) Am J Physiol Heart Circ Physiol 290:H1427-H1432 (PubMed)

Pandalai PK, Bulcao CF, Merrill WH, Akhter SA. Restoration of Myocardial b-Adrenergic Receptor Signaling Following Left Ventricular Assist Device Support. (2006) J Thorac Cardiovasc Surg 131:975-980 (PubMed)

McLean KM, Duffy JY, Pandalai PK, Lyons JM, Bulcao CF, Wagner CJ, Akhter SA, Pearl JM. Glucocorticoids Alter the Balance Between Pro- and Anti-Inflammatory Mediators in the Myocardium in an Experimental Model of Brain Death. (2007) J Heart Lung Transplant 26(1):78-84 (PubMed)

McLean KM, Pandalai PK, Pearl JM, Bulcao CF, Lyons JM, Wagner CJ, Akhter SA, Duffy JY. Beta-Adrenergic Receptor Antagonism Preserves Myocardial Function in an Experimental Model of Brain Death. (2007) J Heart Lung Transplant 26(5):522-528 (PubMed)

D'Souza KM, Petrashevskaya NN, Merrill WH, Akhter SA. Inhibition of Protein Kinase C alpha Improves Myocardial Beta-adrenergic Receptor Signaling and Ventricular Function in a Model of Myocardial Preservation. (2008) J Thorac Cardiovasc Surg. 135(1):172-9, 179.e1. (PubMed)

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