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Beth M. Stadtmueller

Assistant Professor of Biochemistry

Research Interests

Research Topics

Host-Pathogen Interactions, Molecular Immunology, Protein Dynamics, Protein Structure, Virology

Disease Research Interests

Infectious Diseases

Research Description

Antibody structure, antibody engineering, mucosal immunology, retroviral envelopes, electron paramagnetic resonance, electron microscopy, X-ray crystallography

Host-microbe coevolution has produced intricate interspecies relationships in which countless host and microbial proteins interact, ultimately influencing the fitness of both species. Yet, the molecular mechanisms that define many host-microbe interactions remain unexplored, limiting our ability to understand and influence health and disease. To address this challenge, the Stadmueller Lab studies proteins and protein complexes found in the immune system, bacteria and retroviruses using an approach that combines structural biology and biophysics, (e.g. X-ray crystallography, electron microscopy and electron paramagnetic resonance spectroscopy) with protein engineering and animal models of disease.

The lab focuses on two specific biological topics: (1) We investigate the unknown structures and mechanisms of the predominant mucosal antibody, secretory IgA (SIgA), in order to determine how its poorly understood, polymeric architecture can support both pathogen clearance and commensal microbe homeostasis and how we can engineer antibody-based therapeutics to modulate these two functions. (2) We investigate endogenous retroviral envelope (env) proteins, fusogenic proviral proteins expressed from ancient retroviral DNA elements that have integrated into host genomes over millions of years, in order to determine how retroviral env structures and mechanisms have been co-opted through host evolution to support endogenous functions (e.g. embryo implantation) and how they contribute to disease states such as cancer and HIV infection. The broad, long-term goal of these two projects is to understand how protein structure and function has shaped the relationships between the vertebrate immune system, bacteria and viruses and using that information, to develop protein-based therapeutics that can modulate host-microbe interactions.

Education

B.S. 2003 University of Wisconsin, Madison
Ph.D. 2010 University of Utah
Postdoc. 2011-2018 California Institute of Technology

Highlighted Publications

Representative Publications

Kumar Bharathkar, S.*, Parker, B. W.*, Malyutin, A. G., Haloi, N., Huey-Tubman, E. K., Tajkhorshid, E., Stadtmueller, B. M. (2020). "The structures of secretory and dimeric immunoglobulin A." Elife 9. https://elifesciences.org/articles/56098

Stadtmueller B.M. , Bridges M.D., Dam K-M., Lerch M.T., Huey-Tubman K.E., Hubbell W.L., Bjorkman P.J. (2018) DEER Spectroscopy Measurements Reveal Multiple Conformations of HIV-1 SOSIP Envelopes that Show Similarities with Envelopes on Native Virions. Immunity. 2018 Jul 26. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/30076100

Stadtmueller, B.M. , Yang, Z., Huey-Tubman, K.E., Roberts-Mataric, H., Hubbell, W.L., and Bjorkman, P.J. (2016). Biophysical and biochemical characterization of avian secretory component provides structural insights into the evolution of the polymeric Ig receptor. J Immunol. 197(4): 1408-1414. http://www.ncbi.nlm.nih.gov/pubmed/27412418

Featured “In this Issue:” http://www.jimmunol.org/content/197/4/1007

Stadtmueller, B.M. , Huey-Tubman, K.E., Lopez, C.J., Yang, Z., Hubbell, W.L., and Bjorkman, P.J. (2016). The structure and dynamics of secretory component and its interactions with polymeric immunoglobulins. eLife 5. https://www.ncbi.nlm.nih.gov/pubmed/26943617 Featured in Caltech News: https://www.caltech.edu/news/multitasking-protein-keeps-immune-system-h…

Stadtmueller, B.M.* , Kish-Trier E.*, Ferrell K., Robinson H., Myszka D.G., Formosa, T. Hill, C.P. (2012) Crystal structure of the Pba1/2-proteasome complex and implications for HbYX-dependent proteasome interactions. J Biol Chem 287(44):37371-82. https://www.ncbi.nlm.nih.gov/pubmed/22930756

Stadtmueller, B.M. and Hill, C.P. (2011) “Proteasome Activators.” Mol Cell 41(1): 8-19. https://www.ncbi.nlm.nih.gov/pubmed/21211719

Stadtmueller, B. M. , Ferrell K., Whitby F.G., Heroux A., Robinson H., Myszka D.G., Hill C.P. (2010) Structural models for interactions between the 20S proteasome and its PAN/19S activators. J Biol Chem 285(1): 13-7. https://www.ncbi.nlm.nih.gov/pubmed/19889631

Recent Publications

Diefenbacher, M., Tan, T. J. C., Bauer, D. L. V., Stadtmueller, B. M., Wu, N. C., & Brooke, C. B. (2022). Interactions between Influenza A Virus Nucleoprotein and Gene Segment Untranslated Regions Facilitate Selective Modulation of Viral Gene Expression. Journal of virology, 96(10). https://doi.org/10.1128/jvi.00205-22

Diard, M., Bakkeren, E., Lentsch, V., Rocker, A., Bekele, N. A., Hoces, D., Aslani, S., Arnoldini, M., Böhi, F., Schumann-Moor, K., Adamcik, J., Piccoli, L., Lanzavecchia, A., Stadtmueller, B. M., Donohue, N., van der Woude, M. W., Hockenberry, A., Viollier, P. H., Falquet, L., ... Slack, E. (2021). A rationally designed oral vaccine induces immunoglobulin A in the murine gut that directs the evolution of attenuated Salmonella variants. Nature Microbiology, 6(7), 830-841. https://doi.org/10.1038/s41564-021-00911-1

Tan, T. J. C., Yuan, M., Kuzelka, K., Padron, G. C., Beal, J. R., Chen, X., Wang, Y., Rivera-Cardona, J., Zhu, X., Stadtmueller, B. M., Brooke, C. B., Wilson, I. A., & Wu, N. C. (2021). Sequence signatures of two public antibody clonotypes that bind SARS-CoV-2 receptor binding domain. Nature Communications, 12(1), [3815]. https://doi.org/10.1101/2021.01.26.428356, https://doi.org/10.1038/s41467-021-24123-7

Bharathkar, S. K., Parker, B. W., Malyutin, A. G., Haloi, N., Huey-Tubman, K. E., Tajkhorshid, E., & Stadtmueller, B. M. (2020). The structures of secretory and dimeric immunoglobulin a. eLife, 9, 1-29. [e56098]. https://doi.org/10.7554/eLife.56098

Stadtmueller, B. M., Bridges, M. D., Dam, K. M., Lerch, M. T., Huey-Tubman, K. E., Hubbell, W. L., & Bjorkman, P. J. (2018). DEER Spectroscopy Measurements Reveal Multiple Conformations of HIV-1 SOSIP Envelopes that Show Similarities with Envelopes on Native Virions. Immunity, 49(2), 235-246.e4. https://doi.org/10.1016/j.immuni.2018.06.017

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In the news

  • Professor Stadtmueller was one of ten new faculty hires made in the School of Molecular and Cellular Biology in the last three years. Stadtmueller is an assistant professor of biochemistry, assistant professor of Biomedical and Translational Sciences with the Carle Illinois College of Medicine, and...
  • It has been over 60 years since scientists first identified the molecule that we know today as immunoglobulin (Ig) A. IgA is the predominant class of antibody found in human mucus where it is known as secretory (S) IgA. SIgA functions to bind microbes in extracellular regions such as the gut and...