Department of Pathology & Laboratory Medicine

Muhammad Ashraf, Ph.D.Washington State University, Ph.D., 1968

Dr. Ashraf’s research is focused on molecular and cellular mechanisms of myocardial ischemic injury and identifying therapies that prevent cell damage/death in the ischemic heart. The current therapeutic modalities fail to address the root cause of the problem which is characterized by compromised blood flow to the heart due to coronary artery occlusion and irreversible cardiomyocytes loss. To this end, he is applying two approaches in the research laboratory. The first approach requires careful study of the heart’s intrinsic defense mechanisms. When a mild heart attack occurs, the heart attempts to ward off the serious attack and uses endogenous systems and defenses to minimize cell and tissue damage. This is particularly true when brief reversible ischemic episodes followed by restoration of coronary blood supply precede a heart attack. The understanding of this phenomenon, referred as ‘preconditioning’, will allow identification of the potential approaches through which therapies could be designed. The cardiac protection associated with this ‘preconditioning’ is so powerful that no other pharmacological agent to date has matched its beneficial effect.The major significance of his work is that the effects of ischemic preconditioning can be mimicked via pharmacological interventions using mitochondrial potassium channel openers. Recently he advanced the concept of chronic preconditioning of hearts against lethal ischemia so that the heart can be protected for extended period of time in case the patient suffers an unexpected heart attack. He has also pioneered the novel concept of exploiting the cytoprotective effects of preconditioning to alleviate the problem of donor cell attrition during the acute phase after stem cell engraftment in the infarcted heart

In second line of research, the dead heart muscle after myocardial infarction is being regenerated by bone marrow or cardiac stem cell engraftment. This research is designed to address feasibility of heart cell regeneration in both young and old hearts. Once the heart attack kills the cardiac cells, the damaged muscle is replaced with scar tissue, which impairs the pump function of the heart. Bone marrow cells or cardiac stem cells are multipotent and can be directed to differentiate into desired cell types and given the proper milieu, these cells have a potential in treating a failing heart. Dr Ashraf’s research group has adopted a novel approach of combining stem cell transplantation with therapeutic gene delivery via genetic modulation of the donor cells prior to transplantation. This includes a multimodal approach of combining stem cell transplantation with the delivery of therapeutic genes including Akt, HGF, IGF, angiopoietin-1 and stromal cell deived factor-1a, Gata-4.

Recent Publications:

2.  Xu, M., Kudo, M., Wani, M., Ashraf, M.: Differentiation of Bone Marrow Stromal Cells into Cardiac Phenotype Requires Intercellular Communication with Myocytes. Circulation 110:2655-2665,2004

3.  Wang Y, Haider HKh, Ahmad N, Ashraf M: Mechanisms by which K(ATP) channel openers produce acute and delayed cardioprotection. Vasc Pharmacol. 2005; 42(5-6): 253-64

4.  Uemura R, Xu M, Ahmad N, Ashraf M. Bone marrow stem cells prevent left ventricular remodeling of ischemic heart through paracrine signaling. Circ Res 98: 1414-1421, 2006

5.  Ahmad N, Wang Y, Haider HKh, Wang B, Uzun O, Pasha Z, Ashraf M: Cardiac protection by MitoKATP channels is dependent on Akt translocation from cytosol to mitochondria during late preconditioning. Amer J Physiology, 290:H2402-2408, 2006

6.  Jiang S, Haider HKH, Idris NM, Salim A, Ashraf M. Supportive interaction between cell survival signaling and angio-competent factors enhances donor cell survival and promotes angiomyogenesis for cardiac repair. Circ Res 99:776-784, 2006

7. Jiang S, Haider KhH, Idris NM, Lu G, Ashraf M. Long term effects of mesenchymal cell based multiple gene delivery for cardiac repair. Circulation Research. 99:776-84. 2006

8. Elmadbouh I, Haider KhH, Jiang S, Idris NM, Ashraf M. Ex vivo delivered stromal cell-derived factor-1á promotes stem cell homing and induces angiomyogenesis in the infarcted myocardium. J. Molec Cell Cardiology, doi:10.1016/j.yjmcc.2007.02.001

9. Haider HKh & Ashraf M.: Role of pharmacologically mobilized endogenous bone marrow stem cells for cardiac repair. J Heart Lung Transplantation, 24: 1996-1997, 2005

10. Niagara MI, Haider KhH, Jiang S, Ashraf M. Pharmacologically preconditioned skeletal myoblasts are resistant to oxidative stress and promote angiomyogensis via release of paracrine factors in the infarcted heart. Circulation Research 100: 545-555, 2007

[ The Web at UC | UC Home ]

Questions? Contact Pathology e-mail.
Pathology & Laboratory Medicine; Room 1206 MSB, P.O. Box 670529.
Cincinnati, Ohio 45267-0529 ; (513) 558-4500