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Young Jun Kang, PhD

Assistant Professor Adjunct
Department of Immunology and Microbiology
California Campus
Scripps VIVO Scientific Profile
(858) 784-8432

Research Focus

Immune cell signaling in inflammation: Mechanism and its application

Microbial infection, tissue injury or surgical trauma leads to the release of chemical mediators by immune cells that in turn give rise to the initiation of inflammation in the host. Loss of a balanced immune response regulation leads to several inflammatory disorders such as arthritis, inflammatory bowel disease, and septic shock. Sustained inflammatory cytokine production by macrophages contributes to prolonged cytokine elevation in vivo. Although this sustained cytokine response is believed to play an essential role in maintaining the inflammatory states that accompany or induce many inflammatory diseases, its regulatory mechanism is not fully identified. My research programs mainly focus on the investigation of regulatory mechanism of initiation, sustention, and resolution of inflammation in immune responses, and application to the development of novel therapeutic strategies.

I. Mechanism of 4-1BBL-mediated sustained inflammation: target of anti-inflammation

A member of TNF superfamily, 4-1BBL plays an essential role in controlling sustained TNF production in the response of macrophages to endotoxin. Production of TNF by LPS was not different in wildtype or 4-1BBL-deficient macrophages during the first 3-4 hours after stimulation (early phase), but TNF production was not sustained in 4-1BBL-deficient macrophages as it was in the wildtype macrophages (late phase).The goal is to study the activation and regulatory mechanisms of the 4-1BBL-mediated signaling pathway in sustained inflammatory immune responses. The identification of the sequential signaling pathways in initial and sustained TNF production in LPS-treated macrophages has unveiled how the TNF production is regulated; however, there are still gaps in our knowledge of how the 4-1BBL-mediated signaling pathway controls TNF production. Preliminary results show that 4-1BBL is essential for the resistance to LPS-induced septic shock, and inhibition of 4-1BBL-mediated signaling results in the reduction of TNF production in LPS-stimulated macrophages. Thus this observation may lead to the development of new strategy to treat inflammatory diseases by targeting 4-1BBL.

II. Role of p38α MAPK pathway in the regulation of inflammatory responses: development of therapeutic strategies

         p38α MAPK pathway was discovered and cloned in studying intracellular signaling pathway of inflammatory and stress responses. Evidence to support the importance of the p38α pathway in inflammation comes from several sources, and it is believed that activation of the p38α pathway plays an essential role in inflammation in immune responses. Despite it has been studied vigorously to explain the signaling mechanism, the detailed mechanisms of p38α pathway in innate and adaptive immune cells are unclear. We are currently studying the role of p38a in microbial infection and the inflammatory disorders using mouse models to identify the detailed mechanism of p38a-mediated inflammation for the future therapeutic application.

III. Exploration of the cellular events that control the initiation, sustention and resolution of inflammatory responses.

               Despite intensive and vigorous attempts to resolve the regulation of cell signaling pathways in inflammation and infection, many questions are unanswered. Many signaling molecules that participate in the regulation of inflammation were identified; other important molecules are still being discovered. One of the major concerns in this area is how to control the unnecessary and unbeneficial inflammatory responses that damage the host. It is necessary to discover other molecules that might play a critical role in the regulation of inflammation, which can be the target of anti-inflammation. One attempt is investigating the role of miRNA in the regulation of inflammatory responses by the innate immune cells. The miRNAs play an important role in the development and regulation of immunity. Novel inflammatory signaling pathways that are regulated by miRNA will be identified. 


Ph.D. (Microbiology (Immunology)), Seoul National University 1997
M.S. (Microbiology), Seoul National University 1992
B.S. (Biology), Sogang University 1990

Professional Experience

2016-2017 Assistant Professor Adjunct, Immunology and Microbial Science (IMS), The Scripps Research Institute
2010-2016 Assistant Professor of Immunology, Immunology and Microbial Science (IMS), The Scripps Research Institute
2008-2010 Senior Research Associate, The Scripps Research Institute
2008-2008 Assistant Project Scientist, Moore's Cancer Center, University of California, San Diego
2003-2008 Research Associate, The Scripps Research Institute
1999-2003 Postdoctoral Fellow, Stanford University

Selected References

All Publications

  1. Y. J. Kang*, Bang, B. R., Otsuka, M. and Otsu, K. Tissue-specific regulation of p38a-mediated inflammation in ConA-induced acute liver damage. J. Immunol. 2015. In press. *Corresponding author.
  2. Bang, B. R., S. J. Kim, H. Yagita, M. Croft, and Y. J. Kang*. Inhibition of 4-1BBL-regulated TLR response in macrophages ameliorates endotoxin-induced sepsis in mice. Eur. J. Immunol. 2015. 45(3):886-92. *Corresponding author.
  1. Ma, J. , B.-R. Bang, J. Lu, M. Otsuka,  S. Eun, M. Croft, P. Tobias, J. Han, O. Takeuchi, S. Akira, M. Karin, Yagita, H., and Y. J. Kang*.  The TNF family member 4-1BBL sustains inflammation by interacting with TLR signaling components during late-phase activation. Science Signaling. 2013 Oct 1;6(295):ra87. *Corresponding author.
  2. Yoshikawa T, Otsuka M, Kishikawa T, Takata A, Ohno M, Shibata C, Kang YJ, Yoshida H, and Koike K. Unique haplo-insufficient role of the microRNA-processing molecule Dicer1 in a murine colitis-associated tumorigenesis model. PLoS One. 2013 Sep 2;8(9):e71969.
  3. Ohno M, Shibata C, Kishikawa T, Yoshikawa T, Takata A, Kojima K, Akanuma M, Kang YJ, Yoshida H, Otsuka M, Koike K. The flavonoid apigenin improves glucose tolerance through inhibition of microRNA maturation in miRNA103 transgenic mice. Sci Rep. 2013;3:2553. doi: 10.1038/srep02553.
  4. E.-J. Shim, B.-R. Bang, S.-G. Kang, J. Ma, M. Otsuka, J. Kang, M. Stahl, J. Han, B. Vallance, and Y. J. Kang*.  Activation of p38α in T cells regulates the intestinal host defense against attaching and effacing bacterial infections. J. Immunol. 2013. 191(5):2764-70. *Corresponding author.
  5. Takata A, Otsuka M, Yoshikawa T, Kishikawa T, Hikiba Y, Obi S, Goto T, Kang YJ, Maeda S, Yoshida H, Omata M, Asahara H, and Koike K. MiRNA-140 acts as a liver tumor suppressor by controlling NF-κB activity via directly targeting Dnmt1 expression. Hepatology. 2013. 57:162-70.
  6. Kravchenko VV, Gloeckner C, Stowe GN, Kang YJ, Tobias PS, Mathison JC, Ulevitch RJ, Kaufmann GF, Janda KD. The use of small molecule probes to study spatially separated stimulus-induced signaling pathways. Bioorg Med Chem Lett. 2012 22(5):2043-5
  7. Kojima K, Takata A, Vadnais C, Otsuka M, Yoshikawa T, Akanuma M, Kondo Y, Kang YJ, Kishikawa T, Kato N, Xie Z, Zhang WJ, Yoshida H, Omata M, Nepveu A, and Koike K. MicroRNA122 is a key regulator of α-fetoprotein expression and biologically aggressive behavior of hepatocellular carcinoma. Nat Commun. 2011. 2:338. doi: 10.1038/ncomms1345
  8. Hong, L, M. Lai, M. Chen, C. Xie, R. Liao, Y.J. Kang, C. Xiao, W.Y. Hu, J. Han, and P. Sun. The miR-17-92 cluster of microRNAs confers tumorigenicity by inhibiting oncogene-induced senescence. Cancer Res. 2010. 70:8547-57.
  9. Kang, Y. J., M. Lu, and K.-L. Guan. The TSC1 and TSC2 tumor suppressors are required for proper ER stress response and protect cells from ER stress-induced apoptosis. Cell Death Differ. 2011. 18:133-144
  10. Kang, Y.J.*, M. Otsuka*, A. van den Berg, L. Hong, Z. Huang, X. Wu, D.-W. Zhang, B. A. Vallance, P. S. Tobias, and J. Han. Epithelial p38α Controls Immune Cell Recruitment in the Colonic Mucosa. Plos Pathogen. 2010. 6(6): e1000934.doi:10.1371/journal.ppat.1000934. *, equal contribution.
  11. Otsuka, M., Y. J. Kang, J. Ren, H. Jiang, Y. Wang, M. Omata, and J. Han. Distinct Effects of p38a Deletion in Myeloid Lineage and Gut Epithelia in Mouse Models of Inflammatory Bowel Disease. Gastroenterology. 2010. 138:1237-1239.
  12. Kang, Y.J.*, J. Chen, M. Otsuka, J. Mols, S. Ren, Y. Wang and J. Han. Macrophage deletion of p38a partially impairs LPS-induced cellular activation. J Immunol. 2008, 180: 5075-5082.
  13. Kang, Y.J., S.O. Kim, S. Shimada, M. Otsuka, A. Seit-Nebi, T. Watts, B.S. Kwon, and J. Han. Cell surface 4-1BBL mediates sequential signaling pathways 'downstream' of TLR and is required for sustained TNF production in macrophages. Nat. Immunol. 2007. 8: 601-609.
  14. Kang, Y.J.*, B. Kusler, M. Otsuka, M. Hughes, N. Suzuki, S. Suzuki, W.-C. Yeh, S. Akira, J. Han and P.P. Jones*. Calcineurin negatively regulates Toll-like receptor-mediated activation pathways. J. Immunol. 2007. 179: 4598-4607. *Corresponding authors.
  15. Otsuka, M, Q. Jing, P. Georgel, L. New, J. Chen, J. Mols, Y. J. Kang, Z. Jiang, X. Du, R. Cook, S. C. Das, A. K. Pattnaik, B. Beutler, and J. Han. Hypersusceptibility to Vesicular Stomatitis Virus Infection in Dicer1-Deficient Mice Is Due to Impaired miR24 and miR93 Expression. Immunity. 2007. 27:123-34.