USU Department of Microbiology
and Immunology

Brian C. Schaefer, Ph.D.

Associate Professor

USUHS, Department of Microbiology and Immunology

Ph.D., Harvard University, 1995

bschaefer@usuhs.mil

Research: Role of NF-κB signaling in T cell activation and in vivo immunity

Our research is focused on investigating signaling events that regulate antigen-dependent lymphocyte activation, with particular emphasis on T cell receptor (TCR) activation of NF-κB.  Our experimental approach combines imaging technologies with biochemistry, cell biology, and in vivo models. We are currently focusing on the following major projects:

1. Elucidating the molecular mechanisms and subcellular organization of T cell receptor-regulated NF-κB signaling intermediates.
Our published studies (Schaefer et al PNAS 2004; Rossman et al MBC 2006; Langel et al JBC 2008) have documented that TCR stimulation results in the dramatic subcellular redistribution of key NF-κB signaling intermediates into large cytosolic aggregates and/or vesicular structures.  We are continuing to investigate the mechanistic significance of these structures, testing the hypothesis that these aggregated signaling molecules are sites of active signal transduction and/or sites of degradation of specific signaling intermediates.  These studies are ultimately directed towards understanding the molecular mechanisms responsible for transmitting activating signals from the TCR to NF-κB.  This project also includes elucidating mechanisms whereby these NF-kB activating signals can become deregulated, leading to leukemia and lymphoma.

2. Identifying and characterizing regulatory mechanisms that modulate TCR signals to NF-κB.
Following activation, signaling cascades must be deactivated to restore homeostasis.  The mechanisms that modulate the TCR-to-NF-κB cytoplasmic signaling cascade are not yet well understood.  We are attempting to identify novel molecules and mechanisms that down-modulate NF-κB activation by the TCR.

3. Investigation of the role of immune cells and NF-kB signaling in functional recovery from traumatic brain injury (TBI).
In this project, we are testing the hypothesis that NF-κB-dependent immune responses are a major determinant of functional recovery, post-TBI. Our goals are to define the contribution of specific NF-κB signaling pathways and NF-κB dependent immune mechanisms to TBI outcomes. Modulation of NF-κB activation and/or specific NF-κB dependent immune responses is a potentially powerful approach for developing effective therapeutic interventions for brain injury, and to promote neuroregeneration.
 

Last updated: 10/28/09

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