Boris Reizis, Ph.D.
Our research is focused on the molecular control of stem cell function, blood cell development and malignant transformation, and immune response to pathogens. Major areas of interest in the lab include:
Regulation of self-renewal in normal and malignant cells
Stem cells manifest a unique capacity to differentiate into various cell types while maintaining their own number in an undifferentiated state. The unique property of continuous self-renewal is shared among different stem cell types, including pluripotent embryonic stem cells and adult tissue-specific stem cells such as blood-producing hematopoietic stem cells. We have identified transcription factor Zfx as a critical regulator of self-renewal in both embryonic and hematopoietic stem cells, revealing a novel common mechanism of self-renewal in these otherwise distinct stem cell types.
Current studies focus on the mechanism of Zfx activity and its function in other self-renewing cell types. For instance, we study homeostatic proliferation, a unique process whereby peripheral T lymphocytes maintain their number throughout adult life. Another major interest is the self-renewal of cancer cells, including the cancer-propagating cells ("cancer stem cells") in leukemias. Genetic in vivo models of tumorigenesis are used to characterize the role of Zfx in cancer and cancer stem cells.
Regulation of dendritic cell development and function
Dendritic cells (DC) detect, capture and "present" an invading pathogen 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 DC and interferon-producing plasmacytoid DC (PDC). We are studying transcription factors and signaling pathways involved in lineage specification and function of DC and PDC in immune responses.
Recently, we have identified transcription factor E2-2 as an essential and specific regulator of the PDC lineage in mice and in humans. We now investigate the target genes and mechanism of E2-2 activity in the PDC. In parallel, we develop genetic approaches to study PDC function in immune responses to pathogens and in autoimmune diseases.
- 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. Jun 30. pii: jem.20132121. PMID: 24980046. [Epub ahead of print]
- 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.
- Babbe, H., Chester, N., Leder, P. and Reizis, B. (2007) The Bloom's syndrome helicase is critical for development and function of the abT cell lineage. Mol. Cell. Biol. 27: 1947-1959.
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