Eric J. Sundberg, Ph.D.
Principal Scientist
Protein-protein interactions, T cell activation, therapeutic development
Email: sundberg at bbri.org

Research Summary
Our studies aim to answer the following questions: How do we predict the binding specificities and energies of protein-protein interactions from three-dimensional structures alone? How do we engineer therapeutic molecules that specifically abrogate disease-mediating protein-protein interactions? How do we design more effective cancer immunotherapies by leveraging the power of CD4⁺ T cell responses to tumor antigens? Can we control cellular outcomes by engineering tunable signal transduction pathways?  

Investigations that address the first three inquiries utilize model protein-protein interaction systems centered on molecular contacts between T cell receptor (TCR), major histocompatibility complex (MHC) and superantigen (SAG) molecules. The direct interaction of TCR with antigenic peptide-MHC complexes provides the basis for recognition of foreign pathogens and tumors and is the cornerstone of a functional adaptive immune response. Crosslinking of TCR and MHC by SAG, conversely, elicits massive T cell proliferation and the subsequent release of inordinate levels of pyrogenic cytokines that is implicated in numerous diseases. The myriad interactions within these supramolecular complexes can be exploited to better understand the rules that govern protein-protein interactions, design therapeutics to human disease caused by bioterror reagents and define the structural basis of T cell responses to tumors. Studies concerning the engineering of signal transduction pathways will focus on modifying the molecular interfaces within essential T cell signaling complexes. For more details click here.

Selected Publications
Yang X, Buonpane RA, Moza B, Rahman AK, Wang N, Schlievert PM, McCormick JK, Sundberg EJ, Kranz DM. (2008) Neutralization of multiple staphylococcal superantigens by a single-chain protein consisting of affinity-matured, variable domain repeats. J Infect Dis. In press.

Gangopadhyay SS, Gallant C, Sundberg EJ, Lane WS, Morgan KG. (2008) Regulation of Ca2+/calmodulin kinase II by a small C-terminal domain phosphatase. Biochem J. 412(3), 507-516.

Sundberg, E. J., Andersen, P. S., Gorshkova, I. I. & Schuck, P. (2007). Surface plasmon resonance biosensing in the study of ternary systems of interacting proteins. In Protein Interactions: Biophysical Approaches for the Study of Complex Reversible Systems (Schuck, P., ed.), Vol. 5. Springer, New York.

Lichterfeld, M., Kavanagh, D. G., Williams, K. L., Moza, B., Mui, S. K., Miura, T., Sivamurthy, R., Allgaier, R., Pereyra, F., Trocha, A., Feeney, M., Gandhi, R. T., Rosenberg, E. S., Altfeld, M., Allen, T. M., Allen, R., Walker, B. D., Sundberg, E. J. & Yu, X. G. (2007). A viral CTL escape mutation leading to immunoglobulin-like transcript 4-mediated functional inhibition of myelomonocytic cells. J Exp Med 204, 2813-2824.

Lee, E., Hayes, D. B., Langsetmo, K., Sundberg, E. J. & Tao, T. C. (2007). Interactions between the leucine-zipper motif of cGMP-dependent protein kinase and the C-terminal region of the targeting subunit of myosin light chain phosphatase. J Mol Biol 373, 1198-1212.

Gunther, S., Varma, A. K., Moza, B., Kasper, K. J., Wyatt, A. W., Zhu, P., Rahman, A. K., Li, Y., Mariuzza, R. A., McCormick, J. K. & Sundberg, E. J. (2007). A Novel Loop Domain in Superantigens Extends their T Cell Receptor Recognition Site. J Mol Biol 371, 210-221.

Monaghan, P., Woznica, I., Moza, B., Sundberg, E. J. & Rosenblatt, M. (2007). Recombinant expression and purification of the N-terminal extracellular domain of the parathyroid hormone receptor. Protein Expr Purif 54, 87-93.

Buonpane, R. A., Churchill, H. R., Moza, B., Sundberg, E. J., Peterson, M. L., Schlievert, P. M. & Kranz, D. M. (2007). Neutralization of staphylococcal enterotoxin B by soluble, high-affinity receptor antagonists. Nat Med 13, 725-729

Brouillard, J. N., Gunther, S., Varma, A. K., Gryski, I., Herfst, C. A., Rahman, A. K., Leung, D. Y., Schlievert, P. M., Madrenas, J., Sundberg, E. J. & McCormick, J. K. (2007). Crystal Structure of the Streptococcal Superantigen SpeI and Functional Role of a Novel Loop Domain in T Cell Activation by Group V Superantigens. J Mol Biol 367, 925-934.

Moza, B., Varma, A. K., Buonpane, R.A., Zhu, P., Herfst, C. A., McCormick, J. K., Kranz, D. M., Sundberg, E. J. (2007). Structural basis of T cell specificity and activation by the bacterial superantigen TSST-1. EMBO J, 26:1187-1197.

Moza, B., Buonpane, R. A., Zhu, P., Herfst, C. A., Rahman, A. K., McCormick, J. K., Kranz, D. M. & Sundberg, E. J. (2006). Long-range cooperative binding effects in a T cell receptor variable domain. Proc Natl Acad Sci U S A 103, 9867-9872. abstract

Cho, S., Swaminathan, C. P., Yang, J., Kerzic, M. C., Guan, R., Kieke, M. C., Kranz, D. M., Mariuzza, R. A. & Sundberg, E. J. (2005). Structural basis of affinity maturation and intramolecular cooperativity in a protein-protein interaction. Structure (Camb) 13, 1775-1787. abstract

Yang, J., Swaminathan, C. P., Huang, Y., Guan, R., Cho, S., Kieke, M. C., Kranz, D. M., Mariuzza, R. A. & Sundberg, E. J. (2003). Dissecting cooperative and additive binding energetics in the affinity maturation pathway of a protein-protein interface. J Biol Chem 278, 50412-50421. abstract

Sundberg, E. J., Andersen, P. S., Schlievert, P. M., Karjalainen, K. & Mariuzza, R. A. (2003). Structural, energetic, and functional analysis of a protein-protein interface at distinct stages of affinity maturation. Structure 11, 1151-1161. abstract

PubMed:
Click here for a list of publications (searches the National Library of Medicine's PubMed database.)