 Ph.D. (2001) Ohio State University Pharmacology | Minsoo Kim
Assistant
Professor of Microbiology &
Immunology Primary Appointment: Center Affiliation: Graduate
Degree Programs |
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| Contact Information | ||
| University of Rochester Medical Center 601 Elmwood Avenue, Box 609 Rochester, NY 14642 | Phone:
(585) 276-3917 E-Mail: Minsoo_Kim@urmc.rochester.edu | |
- Research Focus
- Dynamic leukocyte adhesion and migration
- Research Overview
- Introduction
Cell migration is central to many biological and pathological processes, including embryogenesis, tissue repair and regeneration as well as cancer and the inflammatory response. Inflammatory recruitment of leukocytes is critical in initiation and progression of a wide range of diseases. Cell surface adhesion molecule, integrin is a critical component in the effective trafficking of leukocytes. - Current Research
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.
- Recent Publications
- F. L. Christofi, H. Zhang, J. Guzman, J-G. Yu, J. Xue, M. Kim, Y-Z. Wang and H. J. Cooke. 2001. Differential gene expression of adenosine A1, A2a, A2b and A3 receptors in the human enteric nervous system. J. Comp. Neurol. 439(1): 46-64
- M. Kim, H.J. Cooke, N.H. Javed, H.V. Carey, F. L. Christofi and H.E. Raybould. 2001. D-Glucose Releases 5-HT from Human BON Cells as a Model of Enterochromaffin Cells. Gastroenterology 121(6), 1400-1406
- M. Kim, N. H. Javed, J-G. Yu, F. L. Christofi, and H. J. Cooke. 2001. Mechanical stimulation activates Gαq signaling pathways and 5-HT releases from human carcinoid BON cells. J. Clin. Inv. 108(7), 1051-1059
- *M. Kim, C. V. Carman, and T. A. Springer. 2003. Bidirectional transmembrane signaling by cytoplasmic domain separation in integrins. Science 301(5640), 1720-1725 (Highlighted in: Faculty of 1000 (Top 10 paper in Immunology), Science's STKE, Chosun daily)
- F. L. Christofi*, M. Kim*, J. E. Wunderlich, J. Xue, Z. Suntres, A. Cardounel, J. H. Javed, J. G. Yu, I. Grants, H. J. Cooke. 2004. Endogenous adenosine differentially modulates 5-hydroxytryptamine release from a human enterochromaffin cell model. Gastroenterology 127(1), 188-202 (*Co-first authors)
- M. Kim, C. V. Carman, W. Yang, A. Salas, and T. A. Springer. 2004. The primacy of affinity over clustering in regulation of adhesiveness of the integrin αLβ2. J. Cell Biol. 167(6), 1241-1253 (Highlighted in: In this issue, J. Cell Biol. )
- A. Salas, M. Shimaoka, U. Phan, M. Kim, T.A. Springer. 2006. Transition from rolling to firm adhesion can be mimicked by extension of integrin αLβ2 in an intermediate affinity state. J Biol Chem. 281(16):10876-82
- J. Chen, W. Yang, M. Kim, C.V. Carman, and T.A. Springer. 2006. Regulation of outside-in signaling and affinity by the β2 I domain of integrin αLβ2. PNAS. 103(35), 13062-7
- *M. Shimaoka, *M. Kim, E.H. Cohen, W. Yang, N. Astrof, D. Peer, A. Salas, A. Ferrand, T.A. Springer. 2006. AL-57, a Ligand-Mimetic Antibody to Integrin LFA-1, Reveals Chemokineinduced Affinity Upregulation in Lymphocytes. PNAS. 103(38), 13991-6 (*Co-first authors)
- W. Yang, C. Carman, M. Kim, A. Salas, M. Motomu, and T.A. Springer. 2006. A small molecule agonist of an integrin, αLβ2. J Biol Chem, 281(49), 37904-12.
- N. Morin, S. Owolabi, E. Papa, M. Harty, T. Tracy, S. Shaw, M. Kim, and C. saab. 2007. Neutrophils Invade Lumbar Dorsal Root Ganglia After Chronic Constriction Injury of the Sciatic Nerve. J. Neuroimm. 184(1-2): 164-71.
- L.M. Lavigne, X.M. O'Brien, M. Kim, J.W. Janowski, J.E. Albina, J.S. Reichner. Integrin engagement mediates the human polymorphonuclear leukocyte response to a fungal pathogen-associated molecular pattern. J Immunol. 2007 Jun 1; 178(11): 7276-82.
- J. Zhu, C.V. Carman, M. Kim, M. Shimaoka, T.A. Springer, and B.-H. Luo. Requirement of alpha and beta subunit transmembrane helix separation for integrin outside-in signaling. Blood 2007 Oct 1;110(7):2475-83.
- M. Kim, F.L. Christofi , J. Xue, J.M. Robinson, H.J. Cooke. Mechanically evoked 5-hydroxytryptamine release is mediated by caveolin-associated cholesterol rich membrane domains. Neurogastroenterol Motil. 2007 Apr;19(4):309-17.
- S.K. Shaw, S.A. Owolabi, J. Bagley, N. Morin, E. Cheng, B.W. LeBlanc, M. Kim, P. Harty, S.G. Waxman, and C.Y. Saab. Activated Polymorphonuclear Cells promote Injury and Excitability of Dorsal Root Ganglia Neurons. Exp. Neurol. In Press (2008).
- *N.A. Morin, P.W. Oakes, Y.-M. Hyun, D. Lee, E.Y. Chin, M.R. King, T.A. Springer, M. Shimaoka, J.X. Tang, J.S. Reichner, and M. Kim. Non-muscle myosin heavy chain-IIA (My-H9) mediates integrin LFA-1 de-adhesion during T lymphocyte migration. J. Ex. Med. 2008 Jan 21;205(1):195-205. (*Highlighted in: In this issue, J. Ex. Med.)
- Books and Book chapters
- A. Schenkel and M. Kim. 2006. "Adhesion Molecules: Function and Inhibition. In Progress in Inflammation Research," M.J. Parnham, ed. (Basel, Switzerland: Birkhauser Publishing).