Sarah E Ewald

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Primary Appointment

Associate Professor, Microbiology, Immunology, and Cancer Biology

Education

  • BA, Biology, University of Massachusetts, Amherst
  • PhD, Molecular and Cell Biology, University of California, Berkeley
  • Postdoc, Immunoparasitology, Stanford University

Research Disciplines

Biochemistry, Biotechnology, Immunology, Infectious Diseases/Biodefense, Metabolism, Microbiology, Molecular Biology, Neuroimmunology, Neuroscience

Research Interests

Innate immunity, chronic disease, host-parasite interactions, Toxoplasma gondii, proteomics

Research Description

OVERVIEW:
How does the body recognize an infectious organism? During infection, how does it determine when to escalate inflammation for pathogen clearance versus dampen inflammation to prevent damage to self? What are the long term consequences of these 'immunological decisions' in the balance of health and chronic disease?
In the Ewald lab we want to understand how the innate immune system participates in these processes. To ask these questions we are interested in harnessing new technologies to examine human disease. We also study how the immune system interacts with the protozoan parasite Toxoplasma gondii: a pathogen with a long evolutionary relationship with both rodents and humans.
PROJECTS:
How does the innate immune system sense Toxoplasma?
Cell autonomous immune sensors survey the host cell for evidence of infection, often inducing host cell death in effort to kill intracellular pathogens. These pathways ave proving efficacious targets for vaccine development and tumor immune therapies; and dysregulation of these pathways due to genetic polymorphism is associated with a range of autoimmune conditions. Despite a better understanding these responses to bacterial and viral infection relatively little is known about the cell autonomous immune response to the protozoan parasite Toxoplasma gondii. Toxoplasma is perhaps the most successful mammalian parasite. This obligate intracellular organism has evolved strategies to intersect host signaling pathways, use host immune cells to traffic through the body and establishes chronic infection that lasts the life of the host. Parasite transmission absolutely depends on establishing chronic infection. In this way, survival of both host and parasite require an intact immune response. This implies a delicate balance of immune evasion and activation strategies driving parasite selection. We are interested in understanding how the parasite activates and manipulates the cell autonomous immune system particularly in the acute response when immune activation is needed. During chronic infection, however, parasite biology that compromises rodent fitness is beneficial because the parasite is transmitted to definitive feline hosts by predation. Our lab has observed that infected mice become chronically cachectic, a wasting disorder characterized by muscle loss that directly contributes to mortality in almost every chronic disease (including infection, fibrotic diseases, atherosclerosis and cance)r. We are using Toxoplasma infection as a novel model to understand immune and metabolic dysregulation driving chronic cachexia.
Automated Spatially targeted optical microproteomics or autoSTOMP is a novel technique that employs standard 2-photon immunofluorescence microscopy to define subcellular structures and selectively UV-cross link proteins in those structures to a modified biotin tag (UV-bio). Once samples are dissociated, labeled proteins are affinity purified and identified by LC-MS. Since the technique does not require genetic modification and overexpression of a label-targeting protein autoSTOMP can be performed on any primary cell or clinical sample where reagents are available to identify the structure of interest.
Our goal is to use autoSTOMP to understand inflammation and tissue pathology in the human body, where genetic tools and experimental manipulation are limited.
POSITIONS:
The Ewald Lab is currently accepting applications for post doctoral positions. For information contact se2s@virginia.edu
The Ewald lab is accepting graduate trainees through The University of Virginia Biomedical Sciences Graduate Program (BIMS) and Medical Scientist Training Program
http://bims.virginia.edu/
https://mstp.med.virginia.edu/

Personal Statement

The innate immune system is traditionally thought of as the initiator of an immune response. However, these cell types and their effectors are an active part of nearly all long-term infections and chronic diseases. In the Ewald lab we are interested in discovering mechanisms of innate inflammation and understanding how they contribute to the lifetime health and homeostasis of the host.

Training

  • Biodefense & Infectious Diseases Short-Term Training to Increase Diversity in Biomedical Sciences
  • Biotechnology Training Grant
  • Interdisciplinary Training Program in Immunology

Selected Publications

2022

Wincott, C. J., Sritharan, G., Benns, H. J., May, D., Gilabert-Carbajo, C., Bunyan, M., . . . Child, M. A. (2022). Cellular barcoding of protozoan pathogens reveals the within-host population dynamics of <i>Toxoplasma gondii</i> host colonization.. Cell reports methods, 2(8), 100274. doi:10.1016/j.crmeth.2022.100274

2021

Yin, B., Caggiano, L. R., Li, R. -C., McGowan, E., Holmes, J. W., & Ewald, S. E. (2021). Automated Spatially Targeted Optical Microproteomics Investigates Inflammatory Lesions In Situ. JOURNAL OF PROTEOME RESEARCH, 20(9), 4543-4552. doi:10.1021/acs.jproteome.1c00505

2020

Melchor, S. J., Hatter, J. A., Castillo, E. A. L., Saunders, C. M., Byrnes, K. A., Sanders, I., . . . Ewald, S. E. (2020). T. gondii infection induces IL-1R dependent chronic cachexia and perivascular fibrosis in the liver and skeletal muscle. SCIENTIFIC REPORTS, 10(1). doi:10.1038/s41598-020-72767-0

Zhao, X. -Y., & Ewald, S. E. (2020). The molecular biology and immune control of chronic Toxoplasma gondii infection. JOURNAL OF CLINICAL INVESTIGATION, 130(7), 3370-3380. doi:10.1172/JCI136226

Melchor, S. J., Saunders, C. M., Sanders, I., Hatter, J. A., Byrnes, K. A., Coutermarsh-Ott, S., & Ewald, S. E. (2020). IL-1R Regulates Disease Tolerance and Cachexia in Toxoplasma gondii Infection. JOURNAL OF IMMUNOLOGY, 204(12), 3329-3338. doi:10.4049/jimmunol.2000159

Yin, B., Mendez, R., Zhao, X. -Y., Rakhit, R., Hsu, K. -L., & Ewald, S. E. (2020). Automated Spatially Targeted Optical Microproteomics (autoSTOMP) to Determine Protein Complexity of Subcellular Structures. ANALYTICAL CHEMISTRY, 92(2), 2005-2010. doi:10.1021/acs.analchem.9b04396

Young, J. C., Broncel, M., Teague, H., Russell, M. R. G., McGovern, O. L., Renshaw, M., . . . Treeck, M. (2020). Phosphorylation of Toxoplasma gondii Secreted Proteins during Acute and Chronic Stages of Infection. MSPHERE, 5(5). doi:10.1128/mSphere.00792-20

2019

Melchor, S. J., & Ewald, S. E. (2019). Disease Tolerance in Toxoplasma Infection. FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY, 9. doi:10.3389/fcimb.2019.00185

2018

Hatter, J. A., Kouche, Y. M., Melchor, S. J., Ng, K., Bouley, D. M., Boothroyd, J. C., & Ewald, S. E. (2018). Toxoplasma gondii infection triggers chronic cachexia and sustained commensal dysbiosis in mice. PLOS ONE, 13(10). doi:10.1371/journal.pone.0204895

2017

Tosello-Trampont, A., Surette, F. A., Ewald, S. E., & Hahn, Y. S. (2017). Immunoregulatory Role of NK Cells in Tissue Inflammation and Regeneration. FRONTIERS IN IMMUNOLOGY, 8. doi:10.3389/fimmu.2017.00301

2014

Pernas, L., Adomako-Ankomah, Y., Shastri, A. J., Ewald, S. E., Treeck, M., Boyle, J. P., & Boothroyd, J. C. (2014). Toxoplasma Effector MAF1 Mediates Recruitment of Host Mitochondria and Impacts the Host Response. PLOS BIOLOGY, 12(4). doi:10.1371/journal.pbio.1001845

Ewald, S. E., Chavarria-Smith, J., & Boothroyd, J. C. (2014). NLRP1 Is an Inflammasome Sensor for Toxoplasma gondii. INFECTION AND IMMUNITY, 82(1), 460-468. doi:10.1128/IAI.01170-13

2012

Tato, C. M., Joyce-Shaikh, B., Banerjee, A., Chen, Y., Sathe, M., Ewald, S. E., . . . Cua, D. J. (2012). The Myeloid Receptor PILR beta Mediates the Balance of Inflammatory Responses through Regulation of IL-27 Production. PLOS ONE, 7(3). doi:10.1371/journal.pone.0031680

2011

Mouchess, M. L., Arpaia, N., Souza, G., Barbalat, R., Ewald, S. E., Lau, L., & Barton, G. M. (2011). Transmembrane Mutations in Toll-like Receptor 9 Bypass the Requirement for Ectodomain Proteolysis and Induce Fatal Inflammation. IMMUNITY, 35(5), 721-732. doi:10.1016/j.immuni.2011.10.009

Ewald, S. E., Engel, A., Lee, J., Wang, M., Bogyo, M., & Barton, G. M. (2011). Nucleic acid recognition by Toll-like receptors is coupled to stepwise processing by cathepsins and asparagine endopeptidase. JOURNAL OF EXPERIMENTAL MEDICINE, 208(4), 643-651. doi:10.1084/jem.20100682

Ewald, S. E., & Barton, G. M. (2011). Nucleic acid sensing Toll-like receptors in autoimmunity. CURRENT OPINION IN IMMUNOLOGY, 23(1), 3-9. doi:10.1016/j.coi.2010.11.006

Barbalat, R., Ewald, S. E., Mouchess, M. L., & Barton, G. M. (2011). Nucleic Acid Recognition by the Innate Immune System. ANNUAL REVIEW OF IMMUNOLOGY, VOL 29, 29, 185-214. doi:10.1146/annurev-immunol-031210-101340