Bruce H. Horwitz

Department of Pathology
Brigham and Women's Hospital
NRB 630E
77 Avenue Louis Pasteur
Boston MA 02115
Ph: 617-525-4404
Fax: 617-525-4422
email:bhorwitz@rics.bwh.harvard.edu
2 Postdoctoral Fellows

The major focus of my laboratory is to understand the role of the NF-κB family of transcription factors in regulating innate inflammatory responses. NF-κB is generally thought of as a pro-inflammatory agent. However, work from our laboratory has demonstrated that certain NF-κB subunits inhibit the ability of bacteria to induce inflammation in several models, including mouse models for inflammatory bowel diseases and septic shock. Furthermore, NF-κB subunits also play a major role in limiting the ability of bacteria to induce critical pro-inflammatory genes such as IL-12. One of the mechanisms by which NF-κB subunits appear to inhibit pro-inflammatory gene expression is by facilitating the inhibitory potential of IL-10, a critical product of regulatory T cells. This may explain our observations that regulatory T cells are unable to suppress pathological inflammation in mice that lack NF-κB subunits.

Ongoing projects within the laboratory include elucidating the cellular and biochemical pathways by which NF-κB and IL-10 inhibit inflammatory bowel disease, and understanding the role of NF-κB subunits in regulating septic shock.

Papers & Publications:

1. Erdman SE, Fox JG, Dangler CA, Feldman D, Horwitz BH. Inflammatory Bowel Disease in NF-κB-Deficient Mice. J Immunol 2001, 166:1443-1447.
2. Erdman SE., Poutahidis T, Tomczak M, Rogers AB, Cormier K, Plank B, Horwitz BH, Fox JG. 2003. CD4+CD45RBlo CD25+ Regulatory T lymphocytes Inhibit Microbially Induced Colon Cancer in Rag2-Deficient Mice. Am J Path 2003, 162:691-702.
3. Tomczak MF, Erdman SE, Poutahidis T, Rogers AB, Holcombe H, Plank B, Fox JG, and Horwitz BH. NF-κB is Required within the Innate Immune System to Inhibit Microflora-Induced Colitis and Expression of IL-12 p40. J Immunol 2003, 171: 1484-1492.