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Satoru Eguchi, MD, PhD

Associate Professor, Physiology

Telephone:  215-707-0169

Fax:  215-707-5737

Office: Medical Research Building Room 803

Email: seguchi@temple.edu

Department of Physiology

Cardiovascular Research Center

MD, 1987

Tohoku University School of Medicine

Sendai, Japan

 

PhD, 1993

Tokyo Medical and Dental University

Tokyo, Japan

 

Postdoctoral Fellowship, 1994

Vanderbilt University School of Medicine

Nashville, TN

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My lab is currently studying the mechanism of signal transduction of vascular smooth muscle cells (VSMCs) and endothelial cells leading to VSMC remodeling and endothelial dysfunction, respectively.  These two major abnormalities are believed to be the critical points leading to irreversible cardiovascular diseases. 

The subjects include:

1) Signaling of a potent cardiovascular pathogen angiotensin II (AngII) in mediating migration and growth of VSMCs. 

1-A.  EGF receptor transactivation by AngII: My lab is leading this area by several key publications demonstrating the involvement of Gq protein, a metalloprotease (ADAM), HB-EGF, and reactive oxygen species in the EGF receptor transactivation resulting in ERK activation, migration and hypertrophy of VSMCs.  We are currently focusing on identification of ADAM together with its mechanism of activation (Figure). The approaches include cell lines from ADAM deleted mice, dominant-negative mutant expression in VSMC by adenovirus and retrovirus, shedding assay by using HB-EGF/ALP chimera construct, deletion and mutation of ADAM constructs tagged with GFP and GST to analyze protein-protein interaction, phosphorylation, and subcellular localization, and ADAM activity assay by using a fluogenic substrate.  Since EGFR transactivation has been shown in cancer and inflammation, the significances of expected findings are not solely limited in vascular biology and pathophysiology.

1-B. Rho/Rho kinase regulation by AngII.

Although importance of Rho kinase in mediating Ca2+ sensitization in VSMCs is well established, the detailed mechanism by which vasoconstrictors such as AngII mediating Rho kinase activation and whether Rho kinase mediates other pathogenic function of Ang II remain unclear.  We recently found that AngII signals to Rho kinase via PKCdelta and PYK2 leading to JNK-dependent VSMC migration. The research could provide novel mechanisms of vascular diseases induced by vasoconstrictors and our expected findings could be expanded to understand the regulation of small G protein by GPCRs.

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

19901155. Hinoki A, Kimura K, Higuchi S, Eguchi K, Takaguri A, Ishimaru K, Frank GD, Gerthoffer WT, Sommerville LJ, Autieri MV, Eguchi S, p21-Activated Kinase 1 Participates in Vascular Remodeling In Vitro and In Vivo. Inter-American Society of Hypertension. Hypertension :()2009 Nov 9

19095998. Suzuki H, Kimura K, Shirai H, Eguchi K, Higuchi S, Hinoki A, Ishimaru K, Brailoiu E, Dhanasekaran DN, Stemmle LN, Fields TA, Frank GD, Autieri MV, Eguchi S, Endothelial nitric oxide synthase inhibits G12/13 and rho-kinase activated by the angiotensin II type-1 receptor: implication in vascular migration. Arterioscler Thromb Vasc Biol 29:2(217-24)2009 Feb

19064814. Suzuki H, Motley ED, Eguchi K, Hinoki A, Shirai H, Watts V, Stemmle LN, Fields TA, Eguchi S, Distinct roles of protease-activated receptors in signal transduction regulation of endothelial nitric oxide synthase. Hypertension 53:2(182-8)2009 Feb

18779232. Sommerville LJ, Xing C, Kelemen SE, Eguchi S, Autieri MV, Inhibition of allograft inflammatory factor-1 expression reduces development of neointimal hyperplasia and p38 kinase activity. Cardiovasc Res 81:1(206-15)2009 Jan 1

18356277. Ohtsu H, Higuchi S, Shirai H, Eguchi K, Suzuki H, Hinoki A, Brailoiu E, Eckhart AD, Frank GD, Eguchi S, Central role of Gq in the hypertrophic signal transduction of angiotensin II in vascular smooth muscle cells. Endocrinology 149:7(3569-75)2008 Jul

18180404. Nakashima H, Frank GD, Shirai H, Hinoki A, Higuchi S, Ohtsu H, Eguchi K, Sanjay A, Reyland ME, Dempsey PJ, Inagami T, Eguchi S, Novel role of protein kinase C-delta Tyr 311 phosphorylation in vascular smooth muscle cell hypertrophy by angiotensin II. Hypertension 51:2(232-8)2008 Feb

17346243. Higuchi S, Ohtsu H, Suzuki H, Shirai H, Frank GD, Eguchi S, Angiotensin II signal transduction through the AT1 receptor: novel insights into mechanisms and pathophysiology. Clin Sci (Lond) 112:8(417-28)2007 Apr

17293685. Shirai H, Autieri M, Eguchi S, Small GTP-binding proteins and mitogen-activated protein kinases as promising therapeutic targets of vascular remodeling. Curr Opin Nephrol Hypertens 16:2(111-5)2007 Mar

17080158. Suzuki H, Eguchi S, Adiponectin versus angiotensin II: Key pathological role of their misbalance. Kidney Int 70:10(1678-9)2006 Nov

16980435. Suzuki H, Eguchi K, Ohtsu H, Higuchi S, Dhobale S, Frank GD, Motley ED, Eguchi S, Activation of endothelial nitric oxide synthase by the angiotensin II type 1 receptor. Endocrinology 147:12(5914-20)2006 Dec

16923993. Ohtsu H, Suzuki H, Nakashima H, Dhobale S, Frank GD, Motley ED, Eguchi S, Angiotensin II signal transduction through small GTP-binding proteins: mechanism and significance in vascular smooth muscle cells. Hypertension 48:4(534-40)2006 Oct

16840716. Ohtsu H, Dempsey PJ, Frank GD, Brailoiu E, Higuchi S, Suzuki H, Nakashima H, Eguchi K, Eguchi S, ADAM17 mediates epidermal growth factor receptor transactivation and vascular smooth muscle cell hypertrophy induced by angiotensin II. Arterioscler Thromb Vasc Biol 26:9(e133-7)2006 Sep

16769815. Ohtsu H, Dempsey PJ, Eguchi S, ADAMs as mediators of EGF receptor transactivation by G protein-coupled receptors. Am J Physiol Cell Physiol 291:1(C1-10)2006 Jul

16724941. Suzuki H, Frank GD, Utsunomiya H, Higuchi S, Eguchi S, Current understanding of the mechanism and role of ROS in angiotensin II signal transduction. Curr Pharm Biotechnol 7:2(81-6)2006 Apr

16472178. Nakashima H, Suzuki H, Ohtsu H, Chao JY, Utsunomiya H, Frank GD, Eguchi S, Angiotensin II regulates vascular and endothelial dysfunction: recent topics of Angiotensin II type-1 receptor signaling in the vasculature. Curr Vasc Pharmacol 4:1(67-78)2006 Jan

16250862. Suzuki H, Motley ED, Frank GD, Utsunomiya H, Eguchi S, Recent progress in signal transduction research of the angiotensin II type-1 receptor: protein kinases, vascular dysfunction and structural requirement. Curr Med Chem Cardiovasc Hematol Agents 3:4(305-22)2005 Oct

16115037. Ohtsu H, Frank GD, Utsunomiya H, Eguchi S, Redox-dependent protein kinase regulation by angiotensin II: mechanistic insights and its pathophysiology. Antioxid Redox Signal 7:9-10(1315-26)2005 Sep-Oct

15998260. Frank GD, Eguchi S, Motley ED, The role of reactive oxygen species in insulin signaling in the vasculature. Antioxid Redox Signal 7:7-8(1053-61)2005 Jul-Aug

15994438. Ohtsu H, Mifune M, Frank GD, Saito S, Inagami T, Kim-Mitsuyama S, Takuwa Y, Sasaki T, Rothstein JD, Suzuki H, Nakashima H, Woolfolk EA, Motley ED, Eguchi S, Signal-crosstalk between Rho/ROCK and c-Jun NH2-terminal kinase mediates migration of vascular smooth muscle cells stimulated by angiotensin II. Arterioscler Thromb Vasc Biol 25:9(1831-6)2005 Sep

15905175. Mifune M, Ohtsu H, Suzuki H, Nakashima H, Brailoiu E, Dun NJ, Frank GD, Inagami T, Higashiyama S, Thomas WG, Eckhart AD, Dempsey PJ, Eguchi S, G protein coupling and second messenger generation are indispensable for metalloprotease-dependent, heparin-binding epidermal growth factor shedding through angiotensin II type-1 receptor. J Biol Chem 280:28(26592-9)2005 Jul 15

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Postdoctoral Fellows

Akinari Hinoki          akinar.hinoki@temple.edu      T: 215-707-8378
Sadaharu Higuchi  shiguchi@temple.edu              T: 215-707-8378

Keita Kimura            keita.kimura@temple.edu       T: 215-707-8378

Akira Takaguri          takira@temple.edu                   T: 215-707-8378

 

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Kunie Eguchi

Senior Laboratory Technician

T:  215-707-8378

F:  215-707-5737

Email address: kunie.eguchi@temple.edu

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