Department of Microbiology & Immunology

Columbia University in the City of New York
Kang Liu, Ph.D.
Assistant Professor of Microbiology & Immunology
Ph.D., Rockefeller University

Hematopoiesis and function of dendritic cells

Research
The main focus of our laboratory is to understand the cellular and molecular events of hematopoiesis of dendritic cells (DCs). DCs are specialized antigen presenting cells and indispensable initiators of immune response. Having a short life, DCs must be constantly replenished through hematopoiesis, a highly organized cellular and molecular process. Downstream of hematopoetic stem cells, a series of progenitors sequentially lose potential to lymphoid and myeloid cells, thereby becoming increasingly restricted to the DC lineage. Such DC hematopoiesis is tightly regulated by extrinsic factors such as cytokines and tissue environment, and intrinsic factors such as transcription factors, both incompletely understood. The capacity to monitor and isolate DCs and their progenitors, in both mice and humans, enables us to study their differentiation potential and gene expression profiles. Using genetic model and patients samples, in combination with in vitro and in vivo models and bioinformatics approaches, we investigate extrinsic and intrinsic factors regulating DC hematopoiesis in both mice and humans, in health and disease.

In particular we are exploring the following areas:

1. Cellular events and transcriptional regulation of DC hematopoiesis in healthy mice and humans.

2. Dysregulation of DC hematopoiesis in leukemia patients.

3. Stromal cell factors driving DC hematopoiesis.

4. How does CNS infection affect differentiation of DCs in the mouse brain?

The long-term goal of our studies is to search for novel ways to manipulate DC development and activity, and to apply the findings to vaccine development and treatment of infectious disease and cancer.

Selected Publications

  1. Lee, J., Zhou, Y.J., Ma, W., Zhang, W., Aljoufi, A., Luh, T., Lucero, K., Liang, D., Thomsen, M., Bhagat, G., Shen, Y. and Liu, K. (2017) Lineage specification of human dendritic cells is marked by IRF8 expression in hematopoietic stem cells and multipotent progenitors. Nature Immunology 18: 877-888.
  2. Collins, A., Rothman, N., Liu, K. and Reiner, S. (2017) Eomesodermin and T-bet mark developmentally distinct human natural killer cells. JCI Insight 2: e90063. Doi:10.1172.
  3. Liu, K. and Malissen, B. (2016) Advances in methods for studying dendritic cell biology. J. Immunol. Methods 432: 1-3.
  4. Puhr, S., Lee, J., Zvezdova, E., and Liu, K. (2015) Dendritic Cell Development - History, advances, and open questions. Seminars in Immunology 27: 388-396
  5. Lee, J., Breton, G., Aljoufi, A., Zhou, Y.J., Puhr, S., Nussenzweig, M.C. and Liu, K. (2015) Clonal analysis of human dendritic cell progenitor using a stromal cell culture. <>Journal of Immunological Methods 425: 21-26.
  6. Breton, G., Lee, J., Liu, K. and Nussenzweig M.C. (2015) Defining human dendritic cell progenitors by multiparametric flow cytometry. Nature Protocols 10: 1407-1422.
  7. Lee, J., Breton, G., Oliveira T.Y.K., Zhou, Y.J., Aljoufi, A., Puhr, S., Cameron, M.J., Sekaly, R.P., Nussenzweig, M.C.* and Liu, K.* (2015) Restricted dendritic cell and monocyte progenitors in human cord blood and bone marrow. J. Exp. Med. 212: 385-399. *Co-corresponding
  8. Breton, G., Lee, J., Zhou, Y.J., Schreiber, J.J., Keler, T., Puhr, S., Anandasabapathy, N., Schlesinger, S., Caskey, M., Liu, K.* and Nussenzweig, M.C.* (2015) Circulating precursors of human CD1c+ and CD141+ dendritic cells. J. Exp. Med. 212: 401-413 *Co-corresponding
  9. Subramanian, M., Hayes, C.D., Thome, J.J., Thorp, E., Matsushima, G.K., Herz, J., Farber, D.L., Liu, K., Lakshmana, M. and Tabas, I. (2014) An AXL/LRP-1/RANBP9 complex mediates DC efferocytosis and antigen cross-presentation in vivo. J. Clin. Invest. 124:1296-1308.
  10. Franklin, R.A., Liao, W., Sarkar, A., Kim, M.V., Bivona, M.R., Liu, K., Pamer, E.G. and Li, M.O. (2014) The cellular and molecular origin of tumor-associated macrophages. Science 344: 921-925.
  11. Ghosh, H.S., Ceribelli, M., Matos, I., Lazarovici, A., Bussemaker, H.J., 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.
  12. Meredith, M.M., Liu, K., Darrasse-Jeze, G., Kamphorst, A.O., Schreiber, H.A., Guermonprez, P., Idoyaga, J., Cheong, C., Yao, K.H., Niec, R.E. and Nussenzweig, M.C. (2012). Expression of the zinc finger transcription factor zDC (Zbtb46, Btbd4) defines the classical dendritic cell lineage. J. Exp. Med. 209: 1153-1165.
  13. Meredith, M.M., Liu, K., Kamphorst, A.O., Idoyaga, J., Yamane, A., Guermonprez, P., Rihn, S., Yao, K.H., Silva, I.T., Oliveira, T.Y., Skokos, D., Casellas, R. and Nussenzweig, M.C. (2012). Zinc finger transcription factor zDC is a negative regulator required to prevent activation of classical dendritic cells in the steady state. J. Exp. Med. 209: 1583-1593.
  14. 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.
  15. Anandasabapathy, N., Victora, G.D., Meredith, M., Feder, R., Dong, B., Kluger, C., Yao, K., Dustin, M.L., Nussenzweig, M.C., Steinman, R.M. and Liu, K. (2011) Flt3L controls the development of radiosensitive dendritic cells in the meninges and choroid plexus of the steady-state mouse brain. J. Exp. Med. 208: 1695-1705.
  16. Liu, K. and Nussenzweig, M.C. (2010) Origin and development of dendritic cells. Immunol. Rev. 234: 45-54.
  17. Ginhoux, F.*, Liu, K.*, Helft, J., Bogunovic, M., Greter, M., Hashimoto, D., Price, J., Yin, N., Bromberg, J., Lira, S.A., Stanley, E.R., Nussenzweig, M. and Merad, M. (2009) The origin and development of nonlymphoid tissue CD103+ DCs. J. Exp. Med. 206: 3115-3130.
  18. Bogunovic, M., Ginhoux, F., Helft, J., Shang, L., Hashimoto, D., Greter, M., Liu, K., Jakubzick, C., Ingersoll, M.A., Leboeuf, M., Stanley, E.R., Nussenzweig, M., Lira, S.A., Randolph, G.J. and Merad, M. (2009) Origin of the lamina propria dendritic cell network. Immunity 31: 513-525.
  19. Darrasse-Jeze, G., Deroubaix, S., Mouquet, H., Victoria, G., Eisenreich, T., Yao, K., Rudensky, A., Liu, K. and Nussenzweig, M.C. (2009) Feedback of regulatory T cell homeostasis by dendritic cells in vivo. J. Exp. Med. 206: 1853-1862.
  20. Liu, K., Victora, G.D.*, Schwickert, T.A.*, Guermonprez, P., Meredith, M.M., Yao, K., Chu, F.F., Randolph, G.J., Rudensky, A.Y. and Nussenzweig, M. (2009) In vivo analysis of dendritic cell development and homeostasis. Science 324: 392-397.
  21. Waskow, C., Liu, K., Darrasse-Jeze, G., Ginhoux, F., Merad, M., Shengelia, T., Yao, K. and Nussenzweig, M. (2008) Flk2 is required for dendritic cell development in peripheral lymphoid tissues. Nat. Immunol. 9: 676-683.
  22. Bulloch, K., Miller, M.M., Gal-Toth, J., Milner, T.A., Gottfried, A.B., Waters, E.M., Kaunzner, U.W., Liu, K., Lindquist, R., Nussenzweig, M.C., Steinman, R.M. and McEwen, B.S. (2008) CD11c/EYFP trangsgene illuminates a discrete network of dendritic cells within neonatal, adult and injured mouse brain. J. Comp. Neurol. 508: 687-710.
  23. Liu, K., Waskow, C., Liu, X., Yao, K., Hoh, J. and Nussenzweig, M. (2007) Origin of dendritic cells in peripheral lymphoid organs of mice. Nat. Immunol. 8: 578-583.
  24. Dudziak, D., Kamphorst, A.O., Heidkamp, G.F., Buchholz, V.R., Trumpfheller, C., Yamazaki, S., Cheong, C., Liu, K., Lee, H.W., Park, C.G., Steinman R.M. and Nussenzweig, M.C. (2007) Differential antigen processing by dendritic cell subsets in vivo. Science 315: 107-111.

Assistant Professor Kang Liu
Phone: 212-305-0839
Lab Phone: 212-305-3951
Fax: 212-305-1468
Email:  kl2529@columbia.edu


Department of Microbiology & Immunology, Columbia University + 701 W. 168 St., HHSC 1208 New York, NY 10032 Tel. 212-305-3647