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Rehman Lab Research
Jalees Rehman, MD
Office location: COMRB 4113
Office phone: 312-996-5552 Email: jalees@uic.edu
Research projects:
Regenerative stem cells and progenitor cells in the cardiovascular system may lead to exciting novel therapies directed at treating cardiovascular diseases, such as congestive heart failure, cardiomyopathy and severe coronary artery disease. While some preliminary studies using novel cell-based therapies in patients have been promising, these therapies are not yet ready for a routine usage in patients. One key obstacle to the clinical use of stem cells and progenitor cells in cardiovascular disease is the fact that we know so little about the actual biology of stem and progenitor cells in the cardiovascular system. Understanding the mechanisms by which stem and progenitor cells help repair and regenerate the cardiovascular system would allow us to develop very efficient and safe therapies that our research laboratory is therefore studying three core areas of stem and progenitor cell biology:
The discovery of circulating endothelial progenitor cells has suggested that the endothelium may undergo endogenous repair following injury by such circulating EPCs. Our research has helped define and characterize the nature of EPCs by demonstrating that that at least two distinct types of EPCs can be found in the blood: Highly proliferative EPCs that are resistant to cellular senescence because of low expression levels of the senescence mediator p16INK4A and minimally proliferative macrophage-like EPCs that exert their protective effects by secreting angiogenic growth factors or lipid mediators such as endocannabinoids. We are currently exploring the question, whether the adult vasculature contains a heterogeneous population of vascular endothelial cells, some of which may be immature EPCs and repair the vessel wall in response to stress or injury.
Rehman J, Li J, Orschell CM, March KL. Endothelial Progenitor Cells are Derived From Monocyte/Macrophages and Secrete Angiogenic Growth Factors. Circulation 107:1164-1169, 2003.
Opitz CA, Rimmerman N, Zhang Y, Mead LE, Yoder MC, Ingram DA, Rehman J. Endothelial Progenitor Cells Release the Endocannabinoids Anandamide and 2-Arachidonoylglycerol. FEBS Letters, 581(25): 4927-31, 2007.
Zhang Y, Herbert BS, Rajashekhar G, Ingram DA, Yoder MC, Clauss M, Rehman J.Premature senescence of highly proliferative endothelial progenitor cells is induced by tumor necrosis factor-alpha via the p38 mitogen-activated protein kinase pathway.FASEB J. 2009 May;23(5):1358-65.
Zhang Y, Ingram DA, Murphy MP, Saadatzadeh MR, Mead LE, Prater DN, Rehman J. Release of proinflammatory mediators and expression of proinflammatory adhesion molecules by endothelial progenitor cells. Am J Physiol Heart Circ Physiol. 2009 May;296(5):H1675-82.
Mitochondrial metabolism and Reactive Oxygen Species (ROS) as regulators of stem cell differentiation and self-renewal:
Mitochondria have been traditionally seen as a major powerhouse that generates ATP, however recent studies show that mitochondria are critical regulators of cell death and cell proliferation, in part via the release of Reactive Oxygen Species (ROS), which can act as signaling molecules. Our most recent data suggest that mitochondrial activity also regulates the differentiation of both embryonic and adult stem cells, and we are currently identifying the specific pathways by which mitochondria exert this regulator effect.
Archer SL, Marsboom G, Kim GH, Zhang HJ, Toth PT, Svensson EC, Dyck JR, Gomberg-Maitland M, Thébaud B, Husain AN, Cipriani N, Rehman J. Epigenetic attenuation of mitochondrial superoxide dismutase 2 in pulmonary arterial hypertension: a basis for excessive cell proliferation and a new therapeutic target. Circulation. 2010 Jun 22;121(24):2661-71.
Rehman J. Empowering self-renewal and differentiation: the role of mitochondria in stem cells. J Mol Med. 2010 Oct 88(10):981-6.
Adult MSCs have generated a large amount of interest in their therapeutic potential in cardiovascular disease. Unfortunately, transplanted adult MSCs demonstrate only minimal engraftment and survival and this may limit their therapeutic use. In this project, we are a specifically studying the paracrine factors released by MSCs and also improve the engraftment and survival of MSCs. It appears that they do not necessarily differentiate into endothelial cells or cardiomyocytes, but create a microenvironment that permits cardiovascular repair and regeneration.
Rehman J, Traktuev D, Li JL, Merfeld-Clauss S, Temm-Grove CJ, Bovenkerk JE, Pell CL, Johnstone BH, Considine RV, March KL. Secretion of angiogenic and antiapoptotic factors by human adipose stromal cells. Circulation, 109(10): 1292-1298, 2004.
Zhao YD, Ohkawara H, Rehman J, Wary KK, Vogel SM, Minshall RD, Zhao YY, Malik AB. Bone marrow progenitor cells induce endothelial adherens junction integrity by sphingosine-1-phosphate-mediated Rac1 and Cdc42 signaling.
Circulation Research 2009 Sep 25;105(7):696-704
Contact: Lab location: COMRB 4100 Lab phone: 312-996-5793 Lab email: yanminz@uic.edu (Lab manager: Yanmin Zhang) Mail Address: Jalees Rehman, MD Associate Professor of Medicine and Pharmacology University of Illinois at Chicago College of Medicine (M/C 868) 835 S. Wolcott Ave. Rm. E403 Chicago, IL 60612 Lab Members |
