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Eric J. Sundberg, PhD

Academic Title:


Primary Appointment:


Secondary Appointment(s):

Microbiology and Immunology

Administrative Title:

Co-Director, Basic Science Division, In The Institute Of Human Virology

Additional Title:

Co-Director, Basic Science Division, Institute of Human Virology; Co-Director, Structural Biology Shared Service, University of Maryland Greenebaum Cancer Center


Institute of Human Virology, N362

Phone (Primary):

(410) 706-7468

Education and Training

My work has focused on the structural biology of infection and immunity since the beginning of my scientific career, first as a graduate student at Northwestern University (in the laboratory of Dr. Theodore Jardetzky, now at Stanford University), then as a postdoctoral fellow at the Center for Advanced Research in Biotechnology-University of Maryland Biotechnology Institute (CARB-UMBI, now the Institute for Bioscience and Biotechnology Research at the University of Maryland College Park; in the laboratory of Dr. Roy Mariuzza). Within three years of receiving my Ph.D., I became an Assistant Professor at CARB-UMBI, and was awarded an NIH R21 award to support my independent work on superantigen structure and function and the development of protein therapeutics that act as superantigen antagonists. I moved to the Boston Biomedical Research Institute (BBRI) in 2004 to start an independent research group where the extension of my work on superantigens and drug development was supported by an NIH R01 award. I expanded my laboratory’s research scope to incorporate studies aimed at understanding the biophysical bases of additional bacterial and viral pathogenesis mechanisms and countervailing immune responses. In April 2011, I moved my research group to the Institute of Human Virology and the Department of Medicine at the University of Maryland School of Medicine in Baltimore, where I was appointed Associate Professor with tenure and, more recently, promoted to Professor. I also hold a secondary appointment in the Department of Microbiology and Immunology. The scope of my research program continues to expand with additional research projects in bacterial pathogenesis and oncology, innate immunity, chronic inflammatory diseases and glycobiology. My research program has been continuously funded by federal, philanthropic and industrial sources since the inception of my independent laboratory. During this time, I have directed the training of five high school students, twelve undergraduate students, three predoctoral students, three masters students, two doctoral students, nine postdoctoral fellows, one Faculty Research Associate and one Assistant Professor. Additionally, I have served as a member of eight Thesis Examination Committees at the University of Maryland School of Medicine, Harvard Medical School and Harvard Dental School. My trainees have obtained academic appointments supported by competitive funding, amongst other positions. Beyond the scope of research and mentoring in my laboratory, I have been appointed recently to leadership roles within the Institute of Human Virology, including Co-Director of our Basic Science Division, home to more twenty primary faculty members with a diverse research portfolio. Additionally, I serve as Co-Director of the Structural Biology Shared Service, a core facility of the NCI-designated Greenebaum Comprehensive Cancer Center at the University of Maryland and am Director of the University of Maryland Baltimore X-ray Crystallography Center.


My research program leverages our expertise in structural biology, molecular biophysics and protein engineering to define the molecular bases of infectious diseases and to develop novel protein therapeutics.

1.     Bacterial pathogenesis.

We have numerous projects investigating bacterial pathogenesis focused on protein appendages and molecular machines found on bacterial cell surfaces, including Type IV pili, Type IV secretion systems and flagella, as described below.

Type IV pili are fimbrial appendages found on the surfaces of many bacteria and are important for adhesion, colonization, biofilm formation and horizontal gene transfer. They consist of thousands of copies of one or a few pilin proteins arranged in a superhelical formation that can be actively extended and retracted from the bacterial surface. Type IV pili have been extensively studied in Gram-negative bacteria. We have recently solved the first high-resolution structures of Type IV pilin proteins from a Gram-positive bacterium, Clostridium difficile. We are pursuing structures of the additional C. difficile Type IV pilin proteins, determining the supramolecular architecture of the multi-component pilus, and identifying host cell receptors that they engage.

We are also investigating another gut microbe, Helicobacter pylori, which is the major causative agent of gastric cancer. H. pylori injects an oncoprotein, CagA, through a Type IV Secretion System into gastric epithelial cells where it carries out numerous biological functions, including the dysregulation of kinase-dependent signal transduction cascades and the apoptotic program, to ultimately cause cellular transformation. We are studying how CagA is delivered through the Type IV Secretion System, how other Cag proteins allow the secretion system to specifically engage host cells and the molecular mechanisms by which CagA dysregulates normal host cell functions. We have recently found that an interaction between the H. pylori adhesin protein HopQ and host cell surface CEACAMs is required for CagA translocation, which has led to our investigations of the structure and function of CEACAMs.

In order to infect and colonize the host, many bacteria rely on swimming motility, which is dependent on the formation and function of flagella, propeller-like molecular machines. A single flagellum is composed predominantly of many copies of the flagellin protein, FliC, which are arranged in a superhelical structure that is many times longer than the length of the bacterium. Flagella are built from their distal ends: individual copies of FliC are unfolded, exported through the pore of the growing flagellum and, when they reach the flagellum end, refolded and properly sorted into position in the superhelical structure. The process of FliC refolding and sorting is entirely dependent on the function of FliD, the protein that caps the flagellum. When FliD is dysfunctional or missing, flagella are substantially stunted and bacteria cannot swim. We have recently determined the first high-resolution X-ray crystal structure of any FliD protein from any bacterium and are investigating the structure and function of FliD proteins from a variety of bacteria. 

2.     Antibody effector functions.

We seek to understand how certain bacteria evade the host immune response by modifying the structure of IgG antibodies to defeat functional Fc-Fc gamma receptor interactions. Streptococcus pyogenes secretes an endoglycosidase, EndoS, which specifically cleaves biantennarary complex carbohydrates linked to the IgG Fc domain residue Asn297. The resulting deglycosylated antibodies can no longer bind to Fc gamma receptors and, thus, making them functionally inactive. Having determined the crystal structure of EndoS, we are now focusing on further defining its mechanism of action and to engineer new EndoS variants with unique glycan and protein specificities that could be used as therapeutics to treat autoimmune diseases and in the chemoenzymatic synthesis of homogeneously glycosylated antibodies. In a related project, we are rationally manipulating the IgG Fc domain structure by targeted hyper-glycosylation in order to control the ratio of binding affinities to activating versus inhibitory Fc gamma receptors. These novel Fc variants could improve the efficacies of a wide range of tumor immunotherapy antibodies currently used clinically.

3.     Innate Immunity and inflammatory diseases.

The IL-1 family cytokines, inlcuding IL-1, IL-33 and IL-36, control T helper cell differentiation into various T helper cell lineages such as Th1, Th2 and Th17 cells. These cytokines are important messenger molecules for mounting immune responses to infection, but also can lead to chronic inflammatory diseases. For instance, IL-33 drives T cell lineage commitment to Th2 cells and is critically important in the progression and exacerbation of asthma; IL-36 drives T cells to become Th1 cells and is a key pathogenic component of psoriasis. All of these cytokines function in similar ways: they bind their cognate receptors and recruit the common IL-1 receptor accessory protein (IL-1RAcP), bringing together cytoplasmic TIR domains from each that initiates signal transduction. Several mechanisms exist to regulate the activation of these cytokine signaling pathways, including antagonist cytokines that compete for binding to cognate receptors but inhibit IL-1RAcP recruitment, as well as decoy receptors that do not include TIR domains and, thus, cannot signal. We are determining the molecular determinants of agonist and antagonist signaling through ST2 (the IL-33 receptor) and the IL-36 receptor and utilizing this knowledge to engineer super-antagonists and improved decoy receptors of IL-33 and IL-36 signaling. We are also adopting a strategy of designing decoy peptide inhibitors that is highly effective in blocking Toll-like receptor signaling (TLRs also have cytoplasmic TIR domains) to IL-1 family cytokine signaling.

Research/Clinical Keywords

Structural Biology, Molecular Biophysics, Protein Engineering, Microbiology, Immunology, Cancer

Highlighted Publications

  1. Sandra Postel, Daniel Deredge, Daniel A. Bonsor, Xiong Yu, Kay Diederichs, Saskia Helmsing, Aviv Vromen, Assaf Friedler, Michael Hust, Edward H. Egelman, Dorothy Beckett, Patrick L. Wintrode and Eric J. Sundberg* (2016). Bacterial flagellar capping proteins adopt diverse oligomeric states. eLife, pii: e18857. doi: 10.7554/eLife.18857. [Epub ahead of print] PubMed PMID: 27664419.
  2. Verena Königer, Lea Holsten, Ute Harrison, Benjamin Busch, Eva Loell, Qing Zhoa, Daniel A. Bonsor, Alexandra Roth, Arnaud Kengmo-Tchoupa, Stella I. Smith, Susanna Mueller, Eric J. Sundberg, Wolfgang Zimmerman, Wolfgang Fischer, Christof R. Hauck and Rainer Haas (2016). Helicobacter pylori exploits human CEACAMs via HopQ for adherence and translocation of CagA. Nature Microbiology, in press.
  3. Kurt H. Piepenbrink, Erik Lillehoj, Christian M. Harding, Jason W. Labonte, Xiaotong Zuo, Chelsea A. Rapp, Robert S. Munson Jr., Simeon E. Goldblum, Mario F. Feldman, Jeffrey J. Gray and Eric J. Sundberg* (2016). Structural diversity in the type IV pili of multidrug-resistant Acinetobacter. Journal of Biological Chemistry, pii: jbc.M116.751099. [Epub ahead of print] PubMed PMID: 27634041.
  4. Daniel A. Bonsor, Sebastian Günther, Robert Beadenkopf, Dorothy Beckett and Eric J. Sundberg* (2015). Diverse oligomeric states of CEACAM IgV domains. Proceedings of the National Academy of Sciences of the United States of America, 112(44), 13561-13566.
  5. Tali H. Reingewertz, Anat Iosub-Amir, Daniel A. Bonsor, Guy Mayer, Assaf Friedler, and Eric J. Sundberg* (2015). An intrinsically disordered region in the human proapoptotic protein ASPP2 protein binds to the Helicobacter pylori oncoprotein CagA. Biochemistry, 54(21), 3337-3347.
  6. Daniel A. Bonsor, Kieu T. Pham, Robert Beadenkopf, Kay Diederichs, Rainer Haas, Dorothy Beckett, Wolfgang Fischer, and Eric J. Sundberg* (2015). Integrin engagement by a helical RGD motif is regulated by a pH-induced displacement of a neighboring alpha helix. Journal of Biological Chemistry, 290(20), 12929-12940.
  7. Kurt H. Piepenbrink, Grace A. Maldarelli, Claudia F. Martinez de la Peña, George L. Mulvey, Erik von Rosenvinge, Glen D. Armstrong, Michael S. Donnenberg, and Eric J. Sundberg* (2015). Structural and evolutionary analyses show unique stabilization strategies in the Type IV pili of Clostridium difficile. Structure, 23(2), 385-396.
  8. Sebastian Günther and Eric J. Sundberg* (2014). Molecular determinants of agonist and antagonist signaling through the IL-36 receptor. Journal of Immunology, 193(2), 921-930.
  9. Beatriz Trastoy, Joseph V. Lomino, Brian Pierce, Lester G. Carter, Sebastian Günther, John P. Giddens, Greg A. Snyder, Thomas M. Weiss, Zhiping Weng, Lai-Xi Wang, and Eric J. Sundberg* (2014). Crystal structure of Streptococcus pyogenes EndoS, an immunomodulatory bacterial endoglycosidase specific for human IgG antibodies. Proceedings of the National Academy of Sciences of the United States of America, 111(18), 6714-6719.
  10. Kurt H. Piepenbrink, Grace A. Maldarelli, Claudia F. Martinez de la Peña, George L. Mulvey, Greg A. Snyder, Leon De Masi, Erik von Rosenvinge, Sebastian Günther, Glen D. Armstrong, Michael S. Donnenberg, Eric J. Sundberg* (2014). Structure of Clostridium difficile PilJ exhibits unprecedented divergence from known Type IV pilins. Journal of Biological Chemistry, 289(7), 4334-4345.