Boris Reizis, Ph.D.
Our research is focused on the molecular control of stem cell function, blood cell development and malignant transformation, immune response to pathogens, and the mechanisms of autoimmune response. Major areas of research in the lab include:
Stem cell function in normal and malignant hematopoiesis
Stem cells manifest a unique capacity to differentiate into various cell types while maintaining their own number in an undifferentiated state. We have identified transcription factor Zfx as a critical regulator of self-renewal in both embryonic stem cells and adult blood-producing hematopoietic stem cells. Current studies focus on the role of Zfx and its targets in the self-renewal of transformed cells in leukemia and other cancer types. We are also developing new tools to visualize and trace the activity of stem cells in normal and malignant hematopoiesis.
Dendritic cell development and function
Dendritic cells (DC) detect, capture and "present" invading pathogens to lymphocytes, thus representing a critical link between the innate and adaptive immunity. Dendritic cells include several lineages dedicated to distinct pathogens and immune response types, including the classical DCs (cDCs) and interferon-producing plasmacytoid DC (pDCs). Our studies have identified several transcription factors and signaling pathways that control the development and specification of DCs. Current studies focus on the molecular control of DC function in the steady state and during immune responses.
Innate immune mechanisms in autoimmunity
Aberrant recognition and attack of the body by its own immune system causes autoimmune diseases such as type I diabetes, multiple sclerosis and systemic lupus erythematosus (SLE). We are studying the mechanisms of autoimmune responses focusing on SLE, in which self-DNA and RNA are being targeted by the immune system. We have recently shown an essential role of pDCs in the development of autoantibodies to DNA and RNA and in the ensuing inflammation and pathology. Current studies focus on additional mechanisms of tolerance to self-DNA and its breakdown in SLE.
- Sisirak, V., Ganguly, D., Lewis, K.L., Couillault, C., Tanaka, L., Bolland, S., D'Agati, V., Elkon, K.B. and Reizis, B. (2014) Genetic evidence for the role of plasmacytoid dendritic cells in systemic lupus erythematosus. J. Exp. Med. 211: 1969-1976.
- Palmer, C.J., Galan-Caridad, J.M., Weisberg, S.P., Lei, L., Esquilin, J.M., Croft, G.F., Wainwright, B., Canoll, P., Owens, D.M. and Reizis, B. (2014) Zfx facilitates tumorigenesis caused by activation of the Hedgehog pathway. Cancer Res. 74: 5914-5924.
- Ghosh, H.S., Ceribelli, M., Matos, I., Lazarovici, A., Bussemaker, H., Lasorella, A., Hiebert, S.W., Liu, K., Staudt, L.M. and Reizis, B. (2014) ETO family protein Mtg16 regulates the balance of dendritic cell subsets by repressing Id2. J. Exp. Med. 211: 1623-1635.
- Weisberg, S.P., Smith-Raska, M.R., Esquilin, J.M., Zhang, J., Arenzana, T.L., Lau, C.M., Churchill, M., Pan, H., Klinakis, A., Dixon, J.E., Mirny, L.A., Mukherjee, S. and Reizis, B. (2014) ZFX controls propagation and prevents differentiation of acute T-lymphoblastic and myeloid leukemia. Cell Rep. 6: 528-540.
- Sawai, C.M., Sisirak, V., Ghosh, H.S., Hou, E.Z., Ceribelli, M., Staudt, L.M. and Reizis, B. (2013) Transcription factor Runx2 controls the development and migration of plasmacytoid dendritic cells. J. Exp. Med. 210: 2151-2159.
- Ganguly, D., Haak, S., Sisirak, V. and Reizis, B. (2013) The role of dendritic cells in autoimmunity. Nat. Rev. Immunol. 13: 566-577.
- Lewis, K.L. and Reizis, B. (2012) Dendritic cells: arbiters of immunity and immunological tolerance. Cold Spring Harb. Perspect. Biol. 4: a007401.
- Cervantes-Barragan, L., Lewis, K.L., Firner, S., Thiel, V., Hugues, S., Reith, W., Ludewig, B. and Reizis, B. (2012) Plasmacytoid dendritic cells control T-cell response to chronic viral infection. Proc. Natl. Acad. Sci. U.S.A. 109: 3012-3017.
- Harel, S., Tu, E.Y., Weisberg, S., Esquilin, M., Chambers, S.M., Liu, B., Carson, C.T., Studer. L., Reizis, B. and Tomishima, M.J. (2012) ZFX controls the self-renewal of human embryonic stem cells. PLoS One 7: e42302.
- Reizis, B., Bunin, A., Ghosh, H.S., Lewis, K.L. and Sisirak, V. (2011) Plasmacytoid dendritic cells: recent progress and open questions. Annu. Rev. Immunol. 29: 163-183.
- Lewis, K.L., Caton, M.L., Bogunovic, M., Greter, M., Grajkowska, L.T., Ng, D., Klinakis, A., Charo, I.F., Jung, S., Gommerman, J.L., Ivanov, I.I., Liu, K., Merad, M. and Reizis, B. (2011) Notch2 receptor signaling controls functional differentiation of dendritic cells in the spleen and intestine. Immunity 35: 780-791.
- Melillo, J.A., Song, L., Bhagat, G., Blazquez, A.B., Plumlee, C.R., Lee, C., Berin, C., Reizis, B. and Schindler, C. (2010) Dendritic cell (DC)-specific targeting reveals Stat3 as a negative regulator of DC function. J. Immunol. 184: 2638-2645.
- Ghosh, H.S., Cisse, B., Bunin, A., Lewis, K.L. and Reizis, B. (2010) Continuous expression of the transcription factor e2-2 maintains the cell fate of mature plasmacytoid dendritic cells. Immunity 33: 905-916.
- Bar-On, L., Birnberg, T., Lewis, K.L., Edelson, B.T., Bruder, D., Hildner, K., Buer, J., Murphy, K.M., Reizis, B. and Jung, S. (2010) CX3CR1+ CD8alpha+ dendritic cells are a steady-state population related to plasmacytoid dendritic cells. Proc. Natl. Acad. Sci. U.S.A. 107: 14745-14750.
- Manicassamy, S., Reizis, B., Ravindran, R., Nakaya, H., Salazar-Gonzalez, R.M., Wang, Y.C. and Pulendran, B. (2010) Activation of beta-catenin in dendritic cells regulates immunity versus tolerance in the intestine. Science 329: 849-853.
- Sathaliyawala, T., O'Gorman, W.E., Greter, M., Bogunovic, M., Konjufca, V., Hou, Z.E., Nolan, G.P., Miller, M.J., Merad, M. and Reizis B. (2010) Mammalian target of rapamycin controls dendritic cell development downstream of Flt3 ligand signaling, Immunity 33: 597-606.
- Arenzana, T.L., Smith-Raska, M.R. and Reizis, B. (2009) Transcription factor Zfx controls BCR-induced proliferation and survival of B lymphocytes. Blood 113: 5857-5867.
- Birnberg, T., Bar-On, L., Sapoznikov, A., Caton, M.L., Cervantes-Barragan, L., Makia, D., Krauthgamer, R., Brenner, O., Ludewig, B., Brockschnieder, D., Riethmacher, D., Reizis, B.* and Jung, S*. (2008) Lack of conventional dendritic cells is compatible with normal development and T cell homeostasis, but causes myeloid proliferative syndrome. Immunity 29: 986-997. [*corresponding authors]
- Cisse, B., Caton, M.L., Lehner, M., Maeda, T., Scheu, S., Locksley, R., Holmberg, D., Zweier, C., den Hollander, N.S., Kant, S.G., Holter, W., Rauch, A., Zhuang, Y. and Reizis B. (2008) Transcription factor E2-2 is an essential and specific regulator of plasmacytoid dendritic cell development. Cell 135: 37-48.
- Hou, B., Reizis, B. and DeFranco, A.L. (2008) Toll-like receptor-mediated dendritic cell-dependent and -independent stimulation of innate and adaptive immunity. Immunity 29: 272-82.
- Travis, M.A., Reizis, B., Melton, A.C., Masteller, E., Tang, Q., Proctor, J.M., Wang, Y., Bernstein, X., Huang, X., Reichardt, L.F., Bluestone, J.A. and Sheppard, D. (2007) Loss of integrin alpha(v)beta(8) on dendritic cells causes autoimmunity and colitis in mice. Nature 449: 361-365.
- Caton, M.L., Smith-Raska, M.R. and Reizis, B. (2007) Notch-RBP-J signaling controls the homeostasis of CD8- dendritic cells in the spleen. J. Exp. Med. 204: 1653-1664.
- Galan-Caridad, J.M., Harel, S., Arenzana, T.L., Hou, Z.E., Doetsch, F.K., Mirny, L.A. and Reizis, B. (2007) Zfx controls the self-renewal of embryonic and hematopoietic stem cells. Cell 129: 345-357.
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