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Abdel Karim Sabri, PhD

Abdel Karim Sabri, PhD

 

Associate Professor, Physiology

Associate Professor, Cardiovascular Research Center

Telephone:  215-707-4915; 215-707-3408 (lab)

Fax:  215-707-5737

Office: MERB 1045

Email: sabri@temple.edu

 

Department of Physiology

Cardiovascular Research Center

 

Educational Background:

 

BS, Cell Biology, Rennes I University, Rennes, France

PhD, Cell Biology, Rene Descartes University, Paris, France

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Research Interests:

 

The research goal in the laboratory is to study the molecular and cellular mechanisms involved in cardiac remodeling.  Inflammatory cells and their proteases are considered a key element that orchestrate myocardial repair.  Although beneficial at early stages, inflammatory proteases may contribute to myocyte death and subsequent alterations in both the geometry and mechanical properties of the heart.  Using intact tissue and cell culture models, my laboratory’s research interest focus on elucidating the mechanisms by which inflammatory proteases induce myocyte death and subsequent cardiac remodeling. Representative current projects within the laboratory include: Mechanisms of Cardiac Myocyte Apoptosis Induced by Neutrophil Derived Proteases.  We have shown recently that acute exposure of cathepsin G to adherent cultured cardiomyocytes induced a loss of focal adhesion structures and round up, a phenomenon called anoikis (apoptosis by loss of integrin-mediated cell-matrix contact).  These events are may be triggered by activation of sheddases (metalloproteases family). We also have evidence that left ventricular cathepsin G levels are elevated during the acute phase of volume overload-induced cardiac hypertrophy and injection of cathepsin G directly into the heart lead to subsequent cardiac remodeling similar to that seen during volume overload. The goals of the study are to determine: i) the molecular mechanisms by which cathepsin G triggers the loss of focal adhesion contacts to modulate cardiomyocyte shape and function. ii) how the loss of cell-matrix contacts induces apoptosis in cardiac myocytes.  iii) how inflammatory proteases contribute to cardiac remodeling in vivo.

 

Beta Adrenergic Receptor (B-AR) Signaling in Heart Failure.  Despite clinical data favoring the use of B-AR blockade in the treatment of heart failure, little is known regarding the cellular and the molecular mechanisms underlying the benefit action of this therapy.  The goal of this project is to determine these mechanisms by using animal model of volume overload-induced cardiac hypertrophy and determine the beneficial effects of ?-AR blockade therapy.  The study also uses cultured cardiomyocyte to delineate the signaling pathways involved in B-AR-induced myocyte phenotypic and functional changes.

 

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PUBMED PUBLICATIONS :


Recent Medically Related Publications, Obtained from PubMed (Click on PubMed ID to view abstract)

24583314. Rafiq K, Kolpakov MA, Seqqat R, Guo J, Guo X, Qi Z, Yu D, Mohapatra B, Zutshi N, An W, Band H, Sanjay A, Houser SR, Sabri A, c-Cbl inhibition improves cardiac function and survival in response to myocardial ischemia. Circulation 129:20(2031-43)2014 May 20

23567617. Liu Y, Dillon AR, Tillson M, Makarewich C, Nguyen V, Dell'Italia L, Sabri AK, Rizzo V, Tsai EJ, Volume overload induces differential spatiotemporal regulation of myocardial soluble guanylyl cyclase in eccentric hypertrophy and heart failure. J Mol Cell Cardiol 60:(72-83)2013 Jul

22612137. Cheheltani R, Rosano JM, Wang B, Sabri AK, Pleshko N, Kiani MF, Fourier transform infrared spectroscopic imaging of cardiac tissue to detect collagen deposition after myocardial infarction. J Biomed Opt 17:5(056014)2012 May

22609523. Seqqat R, Guo X, Rafiq K, Kolpakov MA, Guo J, Koch WJ, Houser SR, Dell'italia LJ, Sabri A, Beta1-adrenergic receptors promote focal adhesion signaling downregulation and myocyte apoptosis in acute volume overload. J Mol Cell Cardiol 53:2(240-9)2012 Aug

22203672. Rafiq K, Guo J, Vlasenko L, Guo X, Kolpakov MA, Sanjay A, Houser SR, Sabri A, c-Cbl ubiquitin ligase regulates focal adhesion protein turnover and myofibril degeneration induced by neutrophil protease cathepsin G. J Biol Chem 287:8(5327-39)2012 Feb 17

21156805. Guo J, Gertsberg Z, Ozgen N, Sabri A, Steinberg SF, Protein kinase D isoforms are activated in an agonist-specific manner in cardiomyocytes. J Biol Chem 286:8(6500-9)2011 Feb 25

20671241. Zhang H, Chen X, Gao E, MacDonnell SM, Wang W, Kolpakov M, Nakayama H, Zhang X, Jaleel N, Harris DM, Li Y, Tang M, Berretta R, Leri A, Kajstura J, Sabri A, Koch WJ, Molkentin JD, Houser SR, Increasing cardiac contractility after myocardial infarction exacerbates cardiac injury and pump dysfunction. Circ Res 107:6(800-9)2010 Sep 17

19716828. Kolpakov MA, Seqqat R, Rafiq K, Xi H, Margulies KB, Libonati JR, Powel P, Houser SR, Dell'italia LJ, Sabri A, Pleiotropic effects of neutrophils on myocyte apoptosis and left ventricular remodeling during early volume overload. J Mol Cell Cardiol 47:5(634-45)2009 Nov

19608982. MacDonnell SM, Weisser-Thomas J, Kubo H, Hanscome M, Liu Q, Jaleel N, Berretta R, Chen X, Brown JH, Sabri AK, Molkentin JD, Houser SR, CaMKII negatively regulates calcineurin-NFAT signaling in cardiac myocytes. Circ Res 105:4(316-25)2009 Aug 14

18356543. Sabri A, Rafiq K, Seqqat R, Kolpakov MA, Dillon R, Dell'italia LJ, Sympathetic activation causes focal adhesion signaling alteration in early compensated volume overload attributable to isolated mitral regurgitation in the dog. Circ Res 102:9(1127-36)2008 May 9

17975113. Rafiq K, Hanscom M, Valerie K, Steinberg SF, Sabri A, Novel mode for neutrophil protease cathepsin G-mediated signaling: membrane shedding of epidermal growth factor is required for cardiomyocyte anoikis. Circ Res 102:1(32-41)2008 Jan 4

17110596. Guo J, Sabri A, Elouardighi H, Rybin V, Steinberg SF, Alpha1-adrenergic receptors activate AKT via a Pyk2/PDK-1 pathway that is tonically inhibited by novel protein kinase C isoforms in cardiomyocytes. Circ Res 99:12(1367-75)2006 Dec 8

16690621. Rafiq K, Kolpakov MA, Abdelfettah M, Streblow DN, Hassid A, Dell'Italia LJ, Sabri A, Role of protein-tyrosine phosphatase SHP2 in focal adhesion kinase down-regulation during neutrophil cathepsin G-induced cardiomyocytes anoikis. J Biol Chem 281:28(19781-92)2006 Jul 14

15557365. Lucchesi PA, Sabri A, Belmadani S, Matrougui K, Involvement of metalloproteinases 2/9 in epidermal growth factor receptor transactivation in pressure-induced myogenic tone in mouse mesenteric resistance arteries. Circulation 110:23(3587-93)2004 Dec 7

14970215. Rybin VO, Guo J, Sabri A, Elouardighi H, Schaefer E, Steinberg SF, Stimulus-specific differences in protein kinase C delta localization and activation mechanisms in cardiomyocytes. J Biol Chem 279:18(19350-61)2004 Apr 30

14575310. Sabri A, Steinberg SF, Protein kinase C isoform-selective signals that lead to cardiac hypertrophy and the progression of heart failure. Mol Cell Biochem 251:1-2(97-101)2003 Sep

12707281. Sabri A, Alcott SG, Elouardighi H, Pak E, Derian C, Andrade-Gordon P, Kinnally K, Steinberg SF, Neutrophil cathepsin G promotes detachment-induced cardiomyocyte apoptosis via a protease-activated receptor-independent mechanism. J Biol Chem 278:26(23944-54)2003 Jun 27

12566450. Rybin VO, Sabri A, Short J, Braz JC, Molkentin JD, Steinberg SF, Cross-regulation of novel protein kinase C (PKC) isoform function in cardiomyocytes. Role of PKC epsilon in activation loop phosphorylations and PKC delta in hydrophobic motif phosphorylations. J Biol Chem 278:16(14555-64)2003 Apr 18

12522105. Sabri A, Guo J, Elouardighi H, Darrow AL, Andrade-Gordon P, Steinberg SF, Mechanisms of protease-activated receptor-4 actions in cardiomyocytes. Role of Src tyrosine kinase. J Biol Chem 278:13(11714-20)2003 Mar 28

12242272. Sabri A, Short J, Guo J, Steinberg SF, Protease-activated receptor-1-mediated DNA synthesis in cardiac fibroblast is via epidermal growth factor receptor transactivation: distinct PAR-1 signaling pathways in cardiac fibroblasts and cardiomyocytes. Circ Res 91:6(532-9)2002 Sep 20

11988485. Sabri A, Wilson BA, Steinberg SF, Dual actions of the Galpha(q) agonist Pasteurella multocida toxin to promote cardiomyocyte hypertrophy and enhance apoptosis susceptibility. Circ Res 90:8(850-7)2002 May 3

10860763. Rohde S, Sabri A, Kamasamudran R, Steinberg SF, The alpha(1)-adrenoceptor subtype- and protein kinase C isoform-dependence of Norepinephrine's actions in cardiomyocytes. J Mol Cell Cardiol 32:7(1193-209)2000 Jul

10827135. Sabri A, Muske G, Zhang H, Pak E, Darrow A, Andrade-Gordon P, Steinberg SF, Signaling properties and functions of two distinct cardiomyocyte protease-activated receptors. Circ Res 86:10(1054-61)2000 May 26

10827134. Sabri A, Pak E, Alcott SA, Wilson BA, Steinberg SF, Coupling function of endogenous alpha(1)- and beta-adrenergic receptors in mouse cardiomyocytes. Circ Res 86:10(1047-53)2000 May 26

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Trainees:

 

Postdoctoral Fellows:

 

Khadija Rafiq, PhD             khadija.rafiq@temple.edu

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laboratory personnel:

 

Jianfen Guo

Senior Research Associate

Email address: jianfen.guo@temple.edu

 

Mikhail Kolpakov

Assistant Scientist

Email address: mikhail.kolpakov@temple.edu

 

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