Distinguished Professor of Pharmacology
Ph.D., University of California, Los Angeles
Dr. Karin has spent his entire academic career investigating stress and inflammation signaling covering the entire gamut of research approaches from basic biochemistry through molecular cell biology to animal pathophysiology. After discovering how environmental stress caused by either infection, inflammation or exposure to toxic substances leads to activation of AP-1, NF-κB and other transcription factors, his lab began to examine the role of the key signaling pathways controlling these transcription factors in the pathogenesis of cancer, degenerative and metabolic diseases. The Karin group has identified some of the fundamental mechanisms through which inflammation and obesity promote tumor development and progression and contribute to type II diabetes. They had established the mechanisms through which members of the IL-6 cytokine family contribute to the development of colorectal and liver cancer through activation of STAT3 and other transcription factors. They had also established the complex and cell type specific mechanisms through which NF-κB activation via IκB kinases (IKK) controls development and progression of colon, liver and prostate cancers. They were amongst the first to demonstrate that not only innate immune cells, such as macrophages, but also adaptive immune cells, including T regulatory cells and B lymphocytes, also contribute to tumorigenesis and its progression. Through this work, Dr. Karin has contributed to the founding of the Inflammation and Cancer field.
BMS Focus Areas:
1. Lee, J.H., Budanov, A.V., Park, E.J., Birse, R., Kim, T.E., Perkins, G.A., Ocorr, K., Ellisman, M.H., Bodmer, R., Bier, E., Karin, M. (2010) Sestrin as a feedback inhibitor of TOR that prevents age-related pathologies. Science 327:1223-1228. PMCID: PMC2866632
2. Holzer, R.G., Pa rk, E.-J., Li, N., Tran, H., Chen, M., Choi, C., Solinas, G., Karin, M. (2011) Saturated fatty acids induce c-Src clustering within membrane subdomains leading to JNK activation. Cell 147:173-184. PMCID: PM C3295636
3. He, G., Yu, G.-Y., Temkin, V., Ogata, H., Kuntzen, C., Sakurai, T., Sieghart, W., Peck-Radosavljevic, M., Leffert, H.L., Karin, M. (2010) Hepatocyte IKKβ/NF-κB inhibits tumor promotion and progression by preventing oxidative stress driven STAT3 activation. Cancer Cell 17:286-297.
4. Grivennikov, S., Wang, K., Mucida, D., Stewart, C-A., Schnabl, B., Jauch, D., Taniguchi, K., Yu, G., Österreicher, C.H., Hung, K.E., Datz, C., Feng, Y., Fearon, E.R., Oukka, M., Tessarollo, L., Coppola, V., Yarovinsky, F., Cheroutre, H., Eckmann, L., Trinchieri, G., Karin, M. (2012) Adenoma-linked barrier defects and microbial products drive IL-23/IL-17-mediated tumour growth. Nature 7423:254-8.
5. He, G., Dhar, D., Nakagawa, H., Font-Burgada, J., Ogata, H., Jiang, Y., Shalapour, S., Seki, E., Yost, S., Jepsen, K., Frazer, K., Harismendy, O., Hatziapostolou, M., Iliopoulos, D., Suetsugu, A., Hoffman, R., Tateishi, R., Koike, K., Karin, M. (2013) Identification of liver cancer progenitors whose malignant progression depends on autocrine IL-6 signaling. Cell 155(2):384-96.
6. Nakagawa, H., Umemura, A., Taniguchi, K., Font-Burgada, J., Dhar, D., Ogata, H., Zhong, Z., Valasek, M., Seki, E., Hidalgo, J., Koike, K., Kaufman, R., Karin, M. (2014) ER stress cooperates with hypernutrition to trigger TNF-dependent spontaneous HCC development. Cancer Cell 26(3):331-43.
7. Umemura, A., Park, E.J., Taniguchi, K., Lee, J.H., Shalapour, S., Valasek, M.A., Aghajan, M., Nakagawa, H., Seki, E., Hall, M.N., Karin, M. (2014) Liver Damage, Inflammation and Enhanced Tumorigenesis after Persistent mTORC1 Inhibition. Cell Metabolism 20(1):133-44.