Faculty Profile

Address:
701 West 168th Street
Room 609
New York, NY 10032

Phone: 212-305-5793
Fax: 212-305-1468

bvr2101@columbia.edu

Affiliations
Microbiology

Training Activities
Training Program in Microbiology
Integrated Program in Cellular, Molecular & Biophysical Studies

Research Summary

The development of the immune system involves specification and self-maintenance of hematopoietic stem cells, emergence of common progenitors, lineage commitment, and 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 molecular genetic approaches such as conditional gene targeting and bacterial artificial chromosome (BAC)-mediated transgenesis in mice to elucidate the transcriptional control of select hematopoietic cell types. Two major projects are currently underway:

Stem cell maintenance
Stem cells manifest a unique capacity to differentiate into various cell types (pluripotency) while renewing their own number (maintenance). These qualities are best exemplified by hematopoietic stem cells of the bone marrow, which give rise to all blood cell types and renew themselves throughout adult life. Despite the tremendous therapeutic potential of stem cells, little is known about the mechanisms regulating their self-renewal. We have identified a transcription factor that appears essential for hematopoietic stem cell maintenance. Moreover, it also seems to regulate the proliferation and/or survival of other stem cell types such as embryonic stem cells. We are using these findings to elucidate signals and pathways potentially involved in stem cell function.

Dendritic cell development
Dendritic cells of the body detect, capture and “present” an invading pathogen to the adaptive immune system, thus representing the first line of defense against infections. Although dendritic cells comprise many distinct populations and can be derived from various cellular precursors, they share a set of specific features including direct pathogen recognition, antigen presentation capacity, expression of co-stimulatory signals etc. The regulation of this common program of dendritic cell development is poorly understood. We are using various approaches to identify transcription factors potentially involved in dendritic cell development and function.

Selected Publications

1. Martin CH, Aifantis I, Scimone ML, von Andrian UH, Reizis B, von Boehmer H, Gounari F. Efficient thymic immigration of B220+ lymphoid-restricted bone marrow cells with T precursor potential. Nat Immunol. 2003 Sep;4(9):866-73.

2. Gounari F, Aifantis I, Martin C, Fehling HJ, Hoeflinger S, Leder P, von Boehmer H, Reizis B. Tracing lymphopoiesis with the aid of a pTalpha-controlled reporter gene. Nat Immunol. 2002 May;3(5):489-96.

3. Reizis B, Leder P. Direct induction of T lymphocyte-specific gene expression by the mammalian Notch signaling pathway. Genes Dev. 2002 Feb 1;16(3):295-300.

4. Reizis B, Leder P. The upstream enhancer is necessary and sufficient for the expression of the pre-T cell receptor alpha gene in immature T lymphocytes. J Exp Med. 2001 Oct 1;194(7):979-90.

5. Reizis B, Lee JT, Leder P. Homologous genomic fragments in the mouse pre-T cell receptor alpha (pTa) and Xist loci. Genomics. 2000 Jan 1;63(1):149-52.

6. Reizis B, Leder P. Expression of the mouse pre-T cell receptor alpha gene is controlled by an upstream region containing a transcriptional enhancer. J Exp Med. 1999 May 17;189(10):1669-78.