Juliane Bubeck Wardenburg, M.D., Ph.D.

Professor and Chief
Critical Care

Molecular Microbiology and Microbial Pathogenesis Program
Immunology Program

  • jbubeck@wustl.edu

  • The research in my laboratory is aimed at understanding fundamental principles of the interaction between bacterial pathogens and the human host.

Research Abstract:

The research in my laboratory is aimed at understanding fundamental principles of the interaction between bacterial pathogens and the human host. The ultimate goal for these studies is to define effective preventative and therapeutic strategies to ameliorate human disease. During my postdoctoral research, I began to study Staphylococcus aureus, an aggressive pathogen that causes a wide array of human disease. Through early work on the pathogenesis of S. aureus pneumonia, we defined S. aureus a-toxin as a critical virulence factor in lung infection. These studies were among the first in the field of S. aureus research to unequivocally link specific invasive disease states with a single secreted virulence factor. We utilized this knowledge to demonstrate that targeting a-toxin with active or passive immunization strategies provided a high degree of protection against lethal staphylococcal pneumonia and severe skin infection. Through collaborative clinical translational studies, we have revealed that a native antibody response targeting a-toxin is a correlate of protection against recurrent S. aureus infection in children. Similarly, we have recently demonstrated that an anti-toxin response is a marker for severe influenza-S. aureus co-infection in children, likely indicating that toxin elaboration early in the course of infection potentiates synergistic lung injury observed in co-infection. Our contributions have shaped the current field of S. aureus vaccine research. a-toxin is now a key antigenic target for both active vaccine development and monoclonal antibody-based immunotherapeutics, presently being pursued in clinical development and clinical trials by several major vaccine manufacturers.

Selected Publications:

Choi, V., Herrou, J., Hecht, A.L., Teoh, W.P., Turner, J.R., Crosson, S., and Bubeck Wardenburg, J. Activation of Bacteroides fragilis toxin by a novel bacterial protease contributes to lethal sepsis. 2016 Nature Medicine, 22(5):563-7.

Fiaschi, L., Di Palo, B., Scarselli, M., Pozzi, C., Tomaszewski, K., Galletti, B., Nardi-Dei, V., Arcidiacono, L., Mishra, R., Mori, E., Pallaoro, M., Falugi, F., Torre, A., Fontana, M.R., Soriani, M., Bubeck Wardenburg, J., Grandi, G., Rappuoli, R., Ferlenghi, I., and Bagnoli, F. An auto-assembling detoxified Staphylococcus aureus alpha-hemolysin mimicking the wild type cytolytic toxin. 2016, Clinical and Vaccine Immunology, 23:442-450.

Hecht, A.L., Casterline, B.W., Earley, Z.M., Goo, Y.A., Goodlett, D.R., and Bubeck Wardenburg, J. Strain competition restricts colonization of an enteric pathogen and prevents colitis. 2016, EMBO Reports, 17:1281-1291.

Herrou, J. Choi, V.M., Bubeck Wardenburg, J., and Crosson, S. Activation mechanism of the Bacteroides fragilis cysteine peptidase, Fragipain. 2016, Biochemistry, 55:4077-4084.

Yu, K.A.O., Randolph, A.G., Agan, A., Pediatric Acute Lung Injury and Sepsis Investigators PICFlu Group, and Bubeck Wardenburg, J. Staphylococcus aureus a-toxin response distinguishes severe respiratory virus co-infection with MRSA. 2016, Journal of Infectious Diseases, 214:1638-1646.

Last Updated: 8/2/2017 3:30:43 PM

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