Faculty & Research
 |
Boris Reizis, Ph.D. Immune system development; stem cell function |
Research
The development of the immune system involves specification and self-maintenance of hematopoietic stem cells, lineage commitment, development and peripheral homeostasis of distinct immune cell types. These complex events are regulated by transcription factors and signaling pathways that specify precise cell-and stage-specific patterns of gene expression. We are using mouse molecular genetics to elucidate the transcriptional control of select hematopoietic cell types. Major areas of interest in the lab include:
Stem cell function
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 hematopoietic stem cells. We investigate the mechanisms regulating stem cell self-renewal, including potential common mechanisms shared by embryonic and adult stem cells. We have identified transcription factor Zfx as a critical regulator of self-renewal in both embryonic and hematopoietic stem cells. Current studies focus on the mechanism of Zfx activity in stem cells, its function in other stem cell types, and particularly on its role in malignancy and in self-renewing cancer-propagating cells (“cancer stem cells”).
Dendritic cell development and function
Dendritic cells (DC) detect, capture and "present" an invading pathogen to lymphocytes, thus representing a critical link between innate and adaptive immune system. Dendritic cells include distinct lineages, including "conventional" DC and interferon-producing plasmacytoid DC (PDC). We are studying transcription factors and signaling pathways involved in lineage specification, homeostasis and function of DC and PDC. 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, as well as develop genetic approaches to study PDC function in vivo.
Recent and Notable Articles
- Galan-Caridad J.M., Harel S., Arenzana T.L., Hou Z.E., Doetsch F.K., Mirny L.A., Reizis B. Zfx controls the self-renewal of embryonic and hematopoietic stem cells. Cell. 2007 Apr 20 129 (2): 345-57.
- Caton M.L., Smith-Raska M.R., Reizis B. Notch-RBP-J signaling controls the homeostasis of CD8- dendritic cells in the spleen. J. Exp. Med. 2007 Jul 9;204(7):1653-64
- Travis MA, Reizis B, Melton AC, Masteller E, Tang Q, Proctor JM, Wang Y, Bernstein X, Huang X, Reichardt LF, Bluestone JA, Sheppard D. Loss of integrin alpha(v)beta(8) on dendritic cells causes autoimmunity and colitis in mice. Nature 2007 Sep 20;449(7160):361-5.
- Hou B, Reizis B, DeFranco AL. Toll-like receptor-mediated dendritic cell-dependent and -independent stimulation of innate and adaptive immunity. Immunity 2008 Aug;29(2):272-82.
- Cisse B, Caton ML, Lehner M, Maeda T, Scheu S, Locksley R, Holmberg D, Zweier C, den Hollander NS, Kant SG, Holter W, Rauch A, Zhuang Y, Reizis B. Transcription factor E2-2 is an essential and specific regulator of plasmacytoid dendritic cell development. Cell 2008 Oct. 3;135(1):37-48.