Koichi Kobayashi, MD, PhD
Office phone: 617-582-8020
Preferred contact method: email
Area of ResearchMechanisms of the Innate Immune System
Dana-Farber Cancer Institute
450 Brookline Avenue
Boston, MA 02215
Dr. Kobayashi received his MD and a PhD in immunology from Chiba University in Japan. After graduate work and residency in internal medicine, he focused on immunology research as a postdoctoral fellow at Yale University School of Medicine. He was appointed an associate research scientist at Yale in 2003 and joined Dana-Farber and Harvard Medical School in 2004. Dr. Kobayashi conducts basic research designed to unlock the mechanisms of the innate immune system and inflammatory diseases.
- Investigator Award, Cancer Research Institute, 2006
ResearchMechanisms of the Innate Immune System
The immune system consists of two different but closely related arms: innate and adaptive immunity. The harmonized interaction of these two responses is required for efficient protection against harmful pathogens and cancers. Our laboratory is focusing on the mechanisms of the innate immune system, its connection to the adaptive immune response, and the development of disease caused by dysregulation of the innate immune response.
Signaling of Toll-like receptors.
A variety of microbial products are detected by a family of germline-encoded cell surface receptors called Toll-like receptors (TLRs). TLRs are evolutionarily conserved proteins that recognize specific pathogens or pathogen-associated molecular patterns (PAMPs) and trigger signaling cascades leading to host immune responses and inflammation. One of our goals is to reveal the molecular mechanism of signaling and regulation of the Toll-like receptor system. To achieve this goal, we are using mutant mice that either lack or overexpress genes involved in TLR signaling.
NLR (NBD-LRR) proteins.
This cytoplasmic protein family, termed collectively NLR (NBD-LRR), is characterized by two motifs: a nucleotide binding domain (NBD) and leucine rich repeats (LRR). Genomic sequence analysis revealed that NLRs comprise a very diverse protein family. Mutations of NLR genes are associated with various inflammatory diseases. We are studying the function of this protein family, especially the mechanisms of pathogen detection and signaling cascades and their significance in protection from infectious diseases.
Activation of adaptive immunity by innate immunity.
Activation of innate immunity, either via TLRs or NLR proteins, is the first line of defense against pathogens or cancerous cells and leads to the activation or regulation of lymphocytes, i.e., the adaptive immune system. We are aiming to find the mechanisms involved in the interaction of these two systems by using cells or animals that lack NLR proteins or signaling molecules in the TLR or NLR pathways.
Pathogenesis of inflammatory disease.
Several lines of evidence suggest that poorly regulated activation of the innate immune system could result in chronic inflammatory diseases. Mutations in the Nod2 gene, one of the NLRs, are frequently observed in patients with Crohn's disease, and TLR signaling is essential for lupus pathogenesis in certain strains of mice. We are seeking to understand the mechanisms that lead to inflammatory diseases by studying the dysregulation of the innate immune response.
- Petnicki-Ocwieja, T., Hrncir, T., Yuen-Joyce Liu, Y-J., Biswas, A., Hudcovic, T., Tlaskalova-Hogenovac, H., Kobayashi, K.S. (2009). Nod2 is required for the regulation of commensal microbiota in the intestine.
Proc Natl Acad Sci U S A, 106(37):15813-8.
- Matza, D., Badou, A., Jha, M.K., Willinger, T., Antov, A., Sanjabi, S., Kobayashi, K.S., Marchesi, V.T., Flavell, R.A. (2009). Requirement for AHNAK1-mediated calcium signaling during T lymphocyte cytolysis.
Proc Natl Acad Sci U S A, 106(24):9785-90.
- Shin, S., Case, C.L., Archer, K.A., Nogueira, C.V., Kobayashi, K.S., Flavell, R.A., Roy, C.R., Zamboni, D.S. (2008) Type IV secretion-dependent activation of host MAP kinases induces an increased proinflammatory cytokine response to Legionella pneumophila.
PLoS Pathog. 4(11):e1000220.
- Matza, D., Kobayashi, K. S., Badou, A., Goldsmith-Pestana, K., Masuda, Y., Komuro, A., McMahon-Pratt, D., Marchesi, V. T. and Flavell, R. A. (2008) A scaffold protein, AHNAK1 is required for calcium signaling during T cell activation,
- Wilmanski J. M., Petnicki-Ocwieja T., Kobayashi, K. S. (2008)
NLR proteins: integral members of innate immunity and mediators of inflammatory diseases.
J. Leukoc Biol, 83(1):13-30.
- Pan, Q., Mathison, J., Fearns C., Kranchenko, V., Correia, J.D.S., Hoffman, H., Kobayashi, K., Bertin, J., Grant, E., Coyle, A., Sutterwala, F., Ogura Y., Flavell, R., Ulevitch, R. (2007)
MDP Induced Interleukin-1b processing requires Nod2 and CIAS/NALP3.
J. Leukoc Biol, 82(1):177-83.
- Shinohara, M. L., Lu, L., Bu. J., Werneck, M. B. F, Kobayashi, K. S., Glimcher, L. H., Cantor, H. (2006). Osteopontin expression is essential for production of IFN- by plasmacytoid dendritic cells,
Nat. Immunol 7(5):498-506.
- Zamboni, D. S., Kobayashi, K. S., Kohlsdorf, T., Ogura, Y., Long, E. M., Vance, R. E., Kuida, K., Mariathasan, S., Dixit, V. M., Flavell, R. A., Dietrich, W. F., Roy, C. R. (2006). The Birc1e cytosolic pattern-recognition receptor contributes to the detection and control of Legionella pneumophila infection,
Nat. Immunol 7(3):318-25.
- Kobayashi, K. S., Chamaillard, M., Ogura, Y., Henegariu, O., Inohara, N., Nuez, G., Flavell, R. A. (2005). Nod2-dependent regulation of innate and adaptive immunity in the intestinal tract,
Science 307, 731-4.
- Kobayashi, K., Hernandez, L. D., Galan, J. E., Janeway, C. A., Jr., Medzhitov, R., and Flavell, R. A. (2002). IRAK-M is a negative regulator of Toll-like receptor signaling,
Cell 110, 191-202.
- Kobayashi, K., Inohara, N., Hernandez, L. D., Galan, J. E., Nunez, G., Janeway, C. A., Medzhitov, R., and Flavell, R. A. (2002). RICK/Rip2/CARDIAK mediates signalling for receptors of the innate and adaptive immune systems,
Nature 416, 194-9.
- Meissner, Torsten, PhD
- Biswas, Amlan, PhD
- Lee, Kyoung-Hee, PhD