Brian C. Schaefer, Ph.D.

Brian C. Schaefer, Ph.D.

Brian Schaefer

Name: Brian C. Schaefer, Ph.D.

Department of Primary Appointment: Microbiology & Immunology
Position: USU Faculty
Title: Professor

Affiliated Departments: Molecular & Cell Biology, Emerging Infectious Diseases

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

Email: (link sends e-mail)
Office Phone: (301) 295-3402
Fax Number: (301) 295-1545

Department Website


Ph.D., Harvard University, 1995


Research:  Mechanisms of leukocyte activation in response to infectious agents and cancer

TCR to NF-κB pathway

Our research is focused on investigating signaling events that regulate lymphocyte activation.  Although we have a longstanding interest in T cell receptor (TCR) activation of NF-κB, our work has more recently diversified to include studies of the innate response to a variety of pathogens and cancer.  Our experimental approach combines cutting-edge imaging technologies with biochemistry, cell biology, and in vivo models of infection and tumorigenesis. We are currently focusing on the following major projects:



 Figure 1. The TCR to NF-κB pathway. Following TCR activation, PKCθ is recruited to the immunological synapse. Activated PKCθ phosphorylates CARMA1, resulting in formation of the CARMA1, BCL10, MALT1 (CBM) complex. The CBM complex transmits activating signals that ultimately result in ubiquitination (U) and degradation of the NF-κB inhibitor, IκBα. Following IκBα proteolysis, NF-κB translocates to the nucleus and activates transcription of genes required for T cell proliferation and differentiation.



1. Eucidating the molecular mechanisms and subcellular organization of T cell receptor-regulated NF-κB signaling intermediates.

PKCθ and Bcl10 redistribution after TCR stimulationOur published studies (Schaefer et al PNAS 2004; Rossman et al MBC 2006; Paul et al Immunity 2012; Paul et al., Science Signaling 2014) have documented that TCR stimulation results in the de novo formation of a cytoplasmic signaling structure that we have named the POLKADOTS signalosome. Both signal transmission to NF-κB and limitation of signal transmission by selective autophagy of the signaling adaptor, Bcl10, occur at this site. Currently, we are using “super-resolution” microscopy and other cutting-edge techniques to define nanoscale features of this complex, and to relate those features mechanistically to regulation of signaling.  This NIGMS-funded work is being conducted collaboratively with the group of Dr. Wolgang Losert at the University of Maryland.  Dr. Losert’s group is using advanced mathematical methods to quantify changes in structural features of this signalosome, to suggest novel hypotheses regarding mechanisms of signal transmission. 

Figure 2. PKCθ and Bcl10 redistribution after TCR stimulation. Conalbumin-loaded antigen presenting cells (APC) stimulate D10 T cells, triggering PKCθ (red) translocation to the immunological synapse and Bcl10 (green) clustering in the cytoplasm of T cells, forming the POLKADOTS signalosome.

2. Investigation of the biology of lyssavirus infection.

TCR-activated CD4 T cell with cytoplasmic Bcl10 clusters that co-localize with LC3+ autophagosomesIn collaboration with our Departmental colleague, Dr. Christopher Broder, we are investigating lyssavirus pathogenesis at the cellular and organism level, to identify weaknesses in the viral life cycle that can be exploited to enable an effective host response to these deadly pathogens. The long term goal of this work is to develop strategies for novel therapeutics, which would have efficacy following establishment of infection in the central nervous system. This work is funded by a USU Program Project grant.

Figure 3. TCR-activated CD4 T cell with cytoplasmic Bcl10 clusters that co-localize with LC3+ autophagosomes. Bcl10 (green) and LC3 (red) signals combine to produce yellow at the region of overlap. Blue is cell surface anti-CD4. The fluorescence image is overlayed on a grayscale DIC image.


3. Defining the role of macrophages in immunosuppression in lung cancer.

In this project, our studies are directed toward better defining the role of macrophages in lung cancer-associated immunosuppression. Our long-term goal is to provide data suggesting novel immunotherapy approaches, which may be more broadly successful in lung cancer than current available therapies.  This translational work is a collaborative effort with our USU colleague, Dr. Clifton Dalgard (Anatomy, Physiology, and Genetics) and Murtha Cancer Center/WRNNMC physicians Dr. Corey Carter and Dr. Karen Zeman. This project is funded by a grant from the Murtha Cancer Center.

Beyond the above funded work, we are also pursuing funding for several additional projects related to mechanistic studies of immunity and cancer.

Schaefer Lab

Left-to-right: Brian Schaefer, Trung Ho, Kate Zeigler, Maria Traver, Mouna Lagraoui, Kariana Rios, Celeste Huaman, Chelsi Beauregard (who is actually in the Broder lab, but we claim her as our own)

Selected Publications

Paul S and Schaefer BC. Visualizing TCR-Induced POLKADOTS Formation and NF-κB Activation in the D10 T-Cell Clone and Mouse Primary Effector T Cells. NF-κB: Methods and Protocols, Methods in Molecular Biology, Michael J. May (ed.), 2015; 1280:219-38.

Paul S, Traver MK, Kashyap AK, Washington MA, Latoche JR, and Schaefer BC. T cell receptor signals to NF-κB are transmitted by a cytosolic p62-Bcl10-Malt1-IKK signalosome. Science Signaling. 2014; 7:ra45

Paul S, Kashyap AK, Jia W, He YW, Schaefer BC. Selective Autophagy of the Adaptor Protein Bcl10 Modulates T Cell Receptor Activation of NF-κB. Immunity. 2012; 36:947-58.

Lagraoui M, Latoche JR, Cartwright NG, Sukumar G, Dalgard CL, Schaefer BC. Controlled cortical impact and craniotomy induce strikingly similar profiles of inflammatory gene expression, but with distinct kinetics. Front Neurol. 2012; 3:155

Cartwright NG, Kashyap AK, Schaefer BC. An active kinase domain is required for retention of PKCθ at the T cell immunological synapse. Mol Biol Cell. 2011; 22:3491-7.

Kingeter LM, Paul S, Maynard SK, Cartwright NG, Schaefer BC. Cutting edge: TCR ligation triggers digital activation of NF-κB. J Immunol. 2010; 185:4520-4.

Kingeter LM and Schaefer BC. Malt1 and cIAP2-Malt1 as effectors of NF-κB activation: Kissing cousins or distant relatives? Cell Signal. 2010; 22:9-22.

Kingeter LM and Schaefer BC. Expanding the multicolor capabilities of basic confocal microscopes by employing red and near-infrared quantum dot conjugates. BMC Biotech. 2009; 9:49.

Langel FD, Jain NA, Rossman JS, Kingeter LM, Kashyap AK, and Schaefer BC. Multiple protein domains mediate interaction between Bcl10 and MALT1. J. Biol. Chem. 2008; 283: 32419-31.

Kingeter LM and Schaefer BC.  Loss of PKCθ, Bcl10, or Malt1 selectively impairs proliferation and NF-κB activation in the CD4+ T cell subset. J. Immunol. 2008; 181:6244-54.

Rossman JS, Stoicheva NG, Langel FD, Patterson GH, Lippincott-Schwartz J, and Schaefer BC. POLKADOTS are foci of functional interactions between cytosolic intermediates in T cell receptor-induced activation of NF-κB. Mol. Biol. Cell 2006; 17:2166-76.