Nathan Karin, PhD
Professor of Immunology
PhD, 1992 - Weizmann Institute, Israel
Chemokines in cancer and autoimmune diseases
Research in my laboratory explores the role of chemokines in cancer and autoimmune diseases. Chemokines are small (~8-14 kDa) structurally related chemotactic cytokines that regulate cell trafficking through interactions with specific seven-transmembrane, G protein-coupled receptors (GPCRs).
The laboratory of Nathan Karin focuses on exploring the working hypothesis that aside of attracting CD4+ T cells to the site of inflammation, chemokines also direct the development of CD4+ T cells into subsets (also known as T cell polarization). A key recent manuscript on the subject investigated the interplay between CXCR3 ligands and their role in T cell polarization, showing that one of these ligands (CXCL11) polarizes FOXP3-negative regulatory T cells that restrain autoimmunity (Zohar et al JCI 2014). The group is now focusing on identifying the reciprocal chemokine that polarizes the key natural regulatory T cells, also known as FOXp3+ Tregs.
As for cancer diseases, the group mostly focuses on investigating the role of chemokines in directing the mobilization of bone marrow derived cells from the bone marrow to the blood, and later to the tumor site, to shape tumor microenvironment, and support tumor growth and metastatic spread.
Zohar, Y., Wildbaum, G., Novak, R., Salzman, A.L., Thelen, M., Alon, R., Barsheshet, Y., Karp, C.L. & Karin, N. CXCL11-dependent induction of FOXP3-negative regulatory T cells suppresses autoimmune encephalomyelitis. J Clin Invest 124, 2009-2022 (2014).
Wildbaum, G., Zohar, Y. & Karin, N. Antigen-specific CD25- Foxp3- IFN-gamma(high) CD4+ T cells restrain the development of experimental allergic encephalomyelitis by suppressing Th17. Am J Pathol 176, 2764-2775 (2010).
Sapir, Y., Vitenshtein, A., Barsheshet, Y., Zohar, Y., Wildbaum, G. & Karin, N. A fusion protein encoding the second extracellular domain of CCR5 arrests chemokine-induced cosignaling and effectively suppresses ongoing experimental autoimmune encephalomyelitis. Journal of immunology 185, 2589-2599 (2010).
Karin, N. The multiple faces of CXCL12 (SDF-1alpha) in the regulation of immunity during health and disease. Journal of leukocyte biology 88, 463-473 (2010).
Izhak, L., Wildbaum, G., Weinberg, U., Shaked, Y., Alami, J., Dumont, D., Friedman, B., Stein, A. & Karin, N. Predominant expression of CCL2 at the tumor site of prostate cancer patients directs a selective loss of immunological tolerance to CCL2 that could be amplified in a beneficial manner. Journal of immunology 184, 1092-1101 (2010).
Cancer development can be blocked using soluble chemokine receptors (Izhak et al J. Immunol 2010).