Minsoo Kim
| Title | Associate Professor |
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| Institution | School of Medicine and Dentistry |
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| Department | Microbiology and Immunology in the Center for Vaccine Biology and Immunology |
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| Address | University of Rochester Medical Center
School of Medicine and Dentistry
601 Elmwood Ave, Box 609
Rochester NY 14642
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| Title | Associate Professor |
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| Institution | School of Medicine and Dentistry |
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| Department | Pharmacology and Physiology |
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| 1992 |
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| Honor student of 1992 by Korea University | | 1999 |
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| Digestive Disease Week (DDW) Poster of Distinction | | 2000 |
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| DDW Poster of Distinction | | 2000 |
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| American Digestive Health Foundation Student Abstract Award | | 2001 |
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| DDW Poster of Distinction | | 2005 |
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| Rhode Island Foundation, Medical Research Grant | | 2005 |
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| American Heart Association, Scientist Developmental Grant | | 2007 |
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| Brown University Seed Fund Award (Co-investigator) |
Unlike cells within solid tissues, circulating leukocytes relocate during the course of immune reactions and dynamically adhere and de-adhere to cells of the vasculature and to other immune cells, as well as to components of the extracellular matrix. A subset of integrins (LFA-1, Mac-1, and VLA4) are expressed on leukocytes and play a major role in regulating leukocyte adhesion and recruitment to damaged or infected tissues during inflammatory responses. The activity of integrins to bind ligands is dynamically and tightly regulated through conformational changes from inactive form to the active one that binds ligands with high affinity. Under a wide range of pathologic conditions, these mechanisms of integrin activation are mis-regulated resulting in abnormal leukocyte trafficking, and direct damage to the vasculature and the underlying tissue making leukocyte integrins a promising therapeutic target for anti-inflammation therapy. Therefore, it would be critical to understand how integrins and their ligands bind to one another, the flow of conformational changes from one integrin domain to another, and the connections to other signaling molecules.
In order to visualize the conformational changes in integrin LFA-1 and its dynamic redistribution on the plasma membrane, we applied the quantitative imaging technique FRET (fluorescence resonance energy transfer) to living cells. Our current research focuses on integrin-mediated leukocyte migration during inflammation. By employing advanced imaging techniques including FRET, live cell imaging, 3D confocal-image reconstruction, IRM (interference reflection microscopy), and TIRFM (total internal reflection fluorescence microscopy), we are trying to improve our understanding of the supramolecular/architectural properties of leukocyte integrins with particular emphasis on their relationship with leukocyte migration. In addition, we are interested in visualizing dynamic interactions of intracellular signaling molecules and identifying new molecules that regulate integrin activation during the leukocyte chemotaxis.
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Sarangi PP, Hyun YM, Lerman YV, Pietropaoli AP, Kim M. Role of ß1 Integrin in Tissue Homing of Neutrophils During Sepsis. Shock. 2012 Aug; 38(3):281-7.
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Hyun YM, Sumagin R, Sarangi PP, Lomakina E, Overstreet MG, Baker CM, Fowell DJ, Waugh RE, Sarelius IH, Kim M. Uropod elongation is a common final step in leukocyte extravasation through inflamed vessels. J Exp Med. 2012 Jul 2; 209(7):1349-62.
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Baker CM, Comrie WA, Hyun YM, Chung HL, Fedorchuk CA, Lim K, Brakebusch C, McGrath JL, Waugh RE, Meier-Schellersheim M, Kim M. Opposing roles for RhoH GTPase during T-cell migration and activation. Proc Natl Acad Sci U S A. 2012 Jun 26; 109(26):10474-9.
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Lefort CT, Hyun YM, Kim M. Monitoring integrin activation by fluorescence resonance energy transfer. Methods Mol Biol. 2012; 757:205-14.
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O'Brien XM, Heflin KE, Lavigne LM, Yu K, Kim M, Salomon AR, Reichner JS. Lectin Site Ligation of CR3 Induces Conformational Changes and Signaling. J Biol Chem. 2012 Jan 27; 287(5):3337-48.
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Guan YJ, Zhang Z, Yu C, Ma L, Hu W, Xu L, Gao JS, Chung CS, Wang L, Yang ZF, Fast LD, Chung AS, Kim M, Ayala A, Zhuang S, Zheng S, Chin YE. Phospho-SXXE/D motif mediated TNF receptor 1-TRADD death domain complex formation for T cell activation and migration. J Immunol. 2011 Aug 1; 187(3):1289-97.
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Ma L, Gao JS, Guan Y, Shi X, Zhang H, Ayrapetov MK, Zhang Z, Xu L, Hyun YM, Kim M, Zhuang S, Chin YE. Acetylation modulates prolactin receptor dimerization. Proc Natl Acad Sci U S A. 2010 Nov 9; 107(45):19314-9.
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Lefort CT, Kim M. Human T lymphocyte isolation, culture and analysis of migration in vitro. J Vis Exp. 2010; (40).
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Hu X, Kang S, Lefort C, Kim M, Jin MM. Combinatorial libraries against libraries for selecting neoepitope activation-specific antibodies. Proc Natl Acad Sci U S A. 2010 Apr 6; 107(14):6252-7.
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Sarangi PP, Lee HW, Kim M. Activated protein C action in inflammation. Br J Haematol. 2010 Mar; 148(6):817-33.
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Lefort CT, Hyun YM, Schultz JB, Law FY, Waugh RE, Knauf PA, Kim M. Outside-in signal transmission by conformational changes in integrin Mac-1. J Immunol. 2009 Nov 15; 183(10):6460-8.
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Hyun YM, Chung HL, McGrath JL, Waugh RE, Kim M. Activated integrin VLA-4 localizes to the lamellipodia and mediates T cell migration on VCAM-1. J Immunol. 2009 Jul 1; 183(1):359-69.
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Quinn JA, Graeber CT, Frackelton AR, Kim M, Schwarzbauer JE, Filardo EJ. Coordinate regulation of estrogen-mediated fibronectin matrix assembly and epidermal growth factor receptor transactivation by the G protein-coupled receptor, GPR30. Mol Endocrinol. 2009 Jul; 23(7):1052-64.
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Elphick GF, Sarangi PP, Hyun YM, Hollenbaugh JA, Ayala A, Biffl WL, Chung HL, Rezaie AR, McGrath JL, Topham DJ, Reichner JS, Kim M. Recombinant human activated protein C inhibits integrin-mediated neutrophil migration. Blood. 2009 Apr 23; 113(17):4078-85.
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Hyun YM, Lefort CT, Kim M. Leukocyte integrins and their ligand interactions. Immunol Res. 2009; 45(2-3):195-208.
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Kaba NK, Schultz J, Law FY, Lefort CT, Martel-Gallegos G, Kim M, Waugh RE, Arreola J, Knauf PA. Inhibition of Na+/H+ exchanger enhances low pH-induced L-selectin shedding and beta2-integrin surface expression in human neutrophils. Am J Physiol Cell Physiol. 2008 Nov; 295(5):C1454-63.
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Morin NA, Oakes PW, Hyun YM, Lee D, Chin YE, Chin EY, King MR, Springer TA, Shimaoka M, Tang JX, Reichner JS, Kim M. Nonmuscle myosin heavy chain IIA mediates integrin LFA-1 de-adhesion during T lymphocyte migration. J Exp Med. 2008 Jan 21; 205(1):195-205.
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Shaw SK, Owolabi SA, Bagley J, Morin N, Cheng E, LeBlanc BW, Kim M, Harty P, Waxman SG, Saab CY. Activated polymorphonuclear cells promote injury and excitability of dorsal root ganglia neurons. Exp Neurol. 2008 Apr; 210(2):286-94.
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Zhu J, Carman CV, Kim M, Shimaoka M, Springer TA, Luo BH. Requirement of alpha and beta subunit transmembrane helix separation for integrin outside-in signaling. Blood. 2007 Oct 1; 110(7):2475-83.
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Lavigne LM, O'Brien XM, Kim M, Janowski JW, Albina JE, Reichner JS. Integrin engagement mediates the human polymorphonuclear leukocyte response to a fungal pathogen-associated molecular pattern. J Immunol. 2007 Jun 1; 178(11):7276-82.
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Kim M, Christofi FL, Xue J, Robinson JM, Cooke HJ. Mechanically evoked 5-hydroxytryptamine release is mediated by caveolin-associated cholesterol rich membrane domains. Neurogastroenterol Motil. 2007 Apr; 19(4):309-17.
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Morin N, Owolabi SA, Harty MW, Papa EF, Tracy TF, Shaw SK, Kim M, Saab CY. Neutrophils invade lumbar dorsal root ganglia after chronic constriction injury of the sciatic nerve. J Neuroimmunol. 2007 Mar; 184(1-2):164-71.
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Yang W, Carman CV, Kim M, Salas A, Shimaoka M, Springer TA. A small molecule agonist of an integrin, alphaLbeta2. J Biol Chem. 2006 Dec 8; 281(49):37904-12.
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Shimaoka M, Kim M, Cohen EH, Yang W, Astrof N, Peer D, Salas A, Ferrand A, Springer TA. AL-57, a ligand-mimetic antibody to integrin LFA-1, reveals chemokine-induced affinity up-regulation in lymphocytes. Proc Natl Acad Sci U S A. 2006 Sep 19; 103(38):13991-6.
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Chen J, Yang W, Kim M, Carman CV, Springer TA. Regulation of outside-in signaling and affinity by the beta2 I domain of integrin alphaLbeta2. Proc Natl Acad Sci U S A. 2006 Aug 29; 103(35):13062-7.
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Salas A, Shimaoka M, Phan U, Kim M, Springer TA. Transition from rolling to firm adhesion can be mimicked by extension of integrin alphaLbeta2 in an intermediate affinity state. J Biol Chem. 2006 Apr 21; 281(16):10876-82.
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Kim M, Carman CV, Yang W, Salas A, Springer TA. The primacy of affinity over clustering in regulation of adhesiveness of the integrin {alpha}L{beta}2. J Cell Biol. 2004 Dec 20; 167(6):1241-53.
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Christofi FL, Kim M, Wunderlich JE, Xue J, Suntres Z, Cardounel A, Javed NH, Yu JG, Grants I, Cooke HJ. Endogenous adenosine differentially modulates 5-hydroxytryptamine release from a human enterochromaffin cell model. Gastroenterology. 2004 Jul; 127(1):188-202.
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Kim M, Carman CV, Springer TA. Bidirectional transmembrane signaling by cytoplasmic domain separation in integrins. Science. 2003 Sep 19; 301(5640):1720-5.
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Kim M, Cooke HJ, Javed NH, Carey HV, Christofi F, Raybould HE. D-glucose releases 5-hydroxytryptamine from human BON cells as a model of enterochromaffin cells. Gastroenterology. 2001 Dec; 121(6):1400-6.
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Christofi FL, Zhang H, Yu JG, Guzman J, Xue J, Kim M, Wang YZ, Cooke HJ. Differential gene expression of adenosine A1, A2a, A2b, and A3 receptors in the human enteric nervous system. J Comp Neurol. 2001 Oct 8; 439(1):46-64.
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Kim M, Javed NH, Yu JG, Christofi F, Cooke HJ. Mechanical stimulation activates Galphaq signaling pathways and 5-hydroxytryptamine release from human carcinoid BON cells. J Clin Invest. 2001 Oct; 108(7):1051-9.
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