Kee Jun Kim, Ph.D.
Research Associate Professor
Microbiology, Molecular Genetics and Immunology
Ph.D., University of Tennessee, Knoxville, 1996
Postdoctoral Fellow, University of Virginia, Johns Hopkins University
The blood-brain barrier (BBB) is a structural and functional barrier that is formed by brain microvascular endothelial cells. The BBB protects the brain from harmful substances in the blood stream, while supplying the brain with the required nutrients for proper function. Unlike barriers of non-brain origin that allow relatively free exchange of substances across or between cells, the BBB strictly limits transport into the brain through tight junctions and a low rate of pinocytosis. BBB breakdown is a key component in central nervous system (CNS) associated pathologies. Exposures to infectious agents and brain injuries are known causes of BBB breakdown. However, the mechanisms underlying BBB dysfunction are not fully understood.
Escherichia coli K1 is the most common Gram-negative organism causing neonatal meningitis. Previous studies demonstrated that E. coli K1 invasion/traversal of human brain microvascular endothelial cells (HBMEC) constituting the BBB is a prerequisite for its penetration into the CNS in vivo. Successful E. coli K1 translocation of the BBB requires a high degree of bacteremia, association with and invasion of HBMEC, induction of actin cytoskeleton rearrangements and related signaling pathways, and traversal of live bacteria through the BBB. Using in vivo and in vitro BBB models, the research in my laboratory focuses on bacterial determinants and their interaction with host factors, which will further our understanding of E. coli K1 pathogenesis.
Many pathological conditions such as hemorrhagic and inflammatory brain injuries have been associated with BBB disruption and increased generation of matrix metalloproteinases (MMPs) and thrombin. We are therefore also investigating the molecular mechanisms of MMP- and thrombin-dependent regulation of BBB function.
- Kim, J-C., Kwon, H-J. Xue, C. and Kim, K.J. 2013. Inositol stimulation of human brain microvascular endothelial cells synergistically promotes Cryptococcus traversal across the blood-brain barrier. (submitted to Cellular Microbiology)
- Liu T-B, Kim J-C, Wang Y., Toffaletti, D.L., Eugenin, E., Perfect, J.R., Kim K.J.#, and Xue C.# 2013. Brain inositol is a novel stimulator for promoting Cryptococcus penetration of the blood-brain barrier. (# Co-corresponding authors) PLoS Pathogens 9: e1003247. doi:10.1371/journal.ppat.1003247
- Kim, J-C., Crary, B., Chang, Y.C., Kwon-Chung, K.J. and Kim, K.J. 2012. Cryptococcus neoformans activates RhoGTPases followed by PKC, FAK and ezrin to enhance traversal across the blood-brain barrier. J. Biol. Chem. 287:36147-36157.
- Yao H., Kim, K.J., Duan, M. et al. 2011. Sigma receptor-mediated induction of ALCAM: Implication for increased moncyte adhesion and migration in the central nervous system. J. Neurosci. 31:5942-5955.
- Yao H, Yang Y, Kim KJ, Bethel-Brown C, Gong N, Funa K, Gendelman HE, Su TP, Wang JQ, Buch S. 2010. Molecular mechanisms involving sigma receptor-mediated induction of MCP-1: implication for increased monocyte transmigration. Blood 115:4951-4962
- Taylor JM, Brown M, Nejmeddine M, Kim KJ, Ratner L, Lairmore M, Nicot C. 2009. Novel role for interleukin-2 receptor-Jak signaling in retrovirus transmission. J Virol. 83:11467-11476.
- Nguyen T, Mehta NR, Conant K, Kim KJ, Kerr D, Calabresi PA, Melli G, Hoke A, Schnaar RL, Song H, Ming G-L, Keswani S, and Griffin, JW 2009. Axonal protective effects of the myelin associated glycoprotein. J. Neurosci. 29:630-637
- Bokhari S, Kim KJ, Pinson DM, Slusser J, Yeh H-W, and Parmely MJ 2008. NK cells and interferon-gamma coordinate the formation and function of hepatic granulomas in mice infected with Francisella tularensis LVS. Infect. Immun. 76:1379-1389
- *Kim KJ, *Milward E, Szklarczyk A, Nguyen T, Melli G, Nayak M, Deshpande D, Fitzsimmons C, Hoke A, Kerr D, Calabresi P, and Conant K. 2007. Cleavage of myelin associated glycoprotein by matrix metalloproteinases. J. Neuroimmunol.193:140-148. (*Co-first authors)
- Dhillon NK, Peng F, Bokhari S, Callen S, Shin S-H, Zhu X, Kim KJ, and Buch S. 2007. Cocaine-mediated alteration in tight junction protein expression and modulation of CCL2/CCR2 axis across the blood-brain barrier: Implications for HIV-Demetia. J. Neuroimmune Pharmacol. 3:52-56.
- Nikolskaia OV, Kim YV, Kovbasnjuk O, Kim KJ, and Grab DJ. 2006. Entry of Trypanosoma brucei gambiense into microvascular endothelial cells of the human blood-brain barrier. Int. J. Parasitol. 36:513-519
- Kim KJ, Chung JW and Kim KS. 2005. The 67-kDa laminin receptor promotes CNF1-expressing Escherichia coli K1 internalization into human brain microvascular endothelial cells. J. Biol. Chem. 280:1360-1368.
- Teng CH, Cai M, Shin S, Xie Y, Kim KJ, Khan N, Di Cello FP, and Kim KS. 2005. Escherichia coli K1 RS218 interacts with human brain microvascular endothelial cells via Type 1 fimbriae. Infect. Immun. 73:2923-2931.
- Grab DJ, Perides G, Dumler SJ, Kim KJ, Park J, Kim YV, Nikolskaia O, Choi KS, Stins MF, Kim KS. 2005. Borrelia burgdorferi interactions with an in vitro model of the human blood-brain barrier. Infect. Immun. 73:1014-1022.
- Xie Y*, Kim KJ* and Kim KS. 2004. Current concepts on Escherichia coli K1 translocation of the blood-brain barrier. FEMS Immunol. Med. Microbiol. 42:271-279. (*equal contribution)
- Park J, Kim KJ, Choi K, Grab DJ and Dumler JS. 2004. Anaplasma phogocytophilum AnkA binds to granulocyte DNA and nuclear proteins. Cell. Microbiol. 6:743-751.
- Grab D, Nikolskaia O, Kim YV, Lonsdale-Eccles JD, Ito S, Hara T, Fukuma T, Lyarko E, Kim KJ, Stins M, Delannoy MJ, Rodgers J, and Kim KS. 2004. African Trypanosome interactions with an in vitro model of the human blood-brain barrier. J. Parasitol. 90:970-979.
- Kim KJ, Elliott SJ, Di Cello F, Stins MF and Kim KS. 2003. K1 capsule modulates trafficking of Escherichia coli-containing vacuoles and enhances intracellular bacterial survival in human brain microvascular endothelial cells. Cell. Microbiol. 5:245-252. [Cited in "Faculty in 1000"]
- Chung JW, Hong SJ, Kim KJ, Goti D, Shin S, Dawson VL, Dawson TM and Kim KS. 2003. Identification of the receptor for cytotoxic necrotizing factor-1 of Escherichia coli K1. J. Biol. Chem. 278:16857-16862.
- Khan NA, Shin S, Chung JW, Kim KJ, Elliott S, Wang Y and Kim KS, 2003. Outer membrane protein A and cytotoxic necrotizing factor-1 use diverse signaling mechanisms for Escherichia coli K1 invasion of the central nervous system. Microb. Pathog. 35:35-42.
- Park J, Kim KJ, Grab DJ and Dumler JS.2003. Anaplasma phagocytophilum major surface protein-2 (Msp2) forms multimeric complexes in the bacterial membrane. FEMS Microbiol Lett. 227:243-247.
- Khan NA, Wang Y, Kim KJ, Chung JW, Wass CA and Kim KS. 2002. Cytotoxic necrotizing factor-1 (CNF1) contributes Escherichia coli K1 invasion of the central nervous system. J. Biol. Chem. 277:15607-12.
- Zhang GW, Khan NA, Kim KJ, Stins M and Kim KS. 2002. Transforming growth factor-b increases Escherichia coli K1 adherence, invasion, transcytosis in human brain microvascular endothelial cells. Tiss. Cell Res. 309:281-286.