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Ewald, Sarah

Sarah Ewald

Primary Appointment

Microbiology, Immunology, and Cancer Biology

Contact Information

Carter Immunology Center
Charlottesville, Virginia 22908
Telephone: 434-924-1925
Fax: 434-924-1221
Email: se2s@virginia.edu

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/

Selected Publications

Melchor StephanieJ, Saunders ClaireM, Sanders Imani, Hatter JessicaA, Byrnes Kari, Coutermarsh-Ott Sheryl, Ewald SarahE, IL-1R regulates disease tolerance and cachexia in T. gondii infection, ; The Journal of Immunology. () |

Melchor SJ, Ewald SE, Disease Tolerance in Toxoplasma Infection., 2019; Frontiers in cellular and infection microbiology. 9() 185 PMID: 31245299 | PMCID: PMC6563770

Yin B, Mendez R, Zhao XY, Rakhit R, Hsu KL, Ewald SE, Automated Spatially Targeted Optical Microproteomics (autoSTOMP) to Determine Protein Complexity of Subcellular Structures., 2019; Analytical chemistry. 92(2) 2005-2010 PMID: 31869197 |

Hatter JA, Kouche YM, Melchor SJ, Ng K, Bouley DM, Boothroyd JC, Ewald SE, Toxoplasma gondii infection triggers chronic cachexia and sustained commensal dysbiosis in mice., 2018; PloS one. 13(10) e0204895 PMID: 30379866 | PMCID: PMC6209157

Tosello-Trampont A, Surette FA, Ewald SE, Hahn YS, Immunoregulatory Role of NK Cells in Tissue Inflammation and Regeneration., 2017; Frontiers in immunology. 8() 301 PMID: 28373874 | PMCID: PMC5357635

Pernas L, Adomako-Ankomah Y, Shastri AJ, Ewald SE, Treeck M, Boyle JP, Boothroyd JC, Toxoplasma effector MAF1 mediates recruitment of host mitochondria and impacts the host response., 2014; PLoS biology. 12(4) e1001845 PMID: 24781109 | PMCID: PMC4004538

Ewald SE, Chavarria-Smith J, Boothroyd JC, NLRP1 is an inflammasome sensor for Toxoplasma gondii., 2013; Infection and immunity. 82(1) 460-8 PMID: 24218483 | PMCID: PMC3911858

Tato CM, Joyce-Shaikh B, Banerjee A, Chen Y, Sathe M, Ewald SE, Liu MR, Gorman D, McClanahan TK, Phillips JH, Heyworth PG, Cua DJ, The myeloid receptor PILR? mediates the balance of inflammatory responses through regulation of IL-27 production., 2012; PloS one. 7(3) e31680 PMID: 22479310 | PMCID: PMC3313972

Ewald SE, Engel A, Lee J, Wang M, Bogyo M, Barton GM, Nucleic acid recognition by Toll-like receptors is coupled to stepwise processing by cathepsins and asparagine endopeptidase., 2011; The Journal of experimental medicine. 208(4) 643-51 PMID: 21402738 | PMCID: PMC3135342

Ewald SJ, Kapczynski DR, Livant EJ, Suarez DL, Ralph J, McLeod S, Miller C, Association of Mx1 Asn631 variant alleles with reductions in morbidity, early mortality, viral shedding, and cytokine responses in chickens infected with a highly pathogenic avian influenza virus., 2011; Immunogenetics. 63(6) 363-75 PMID: 21286706 |

Barbalat R, Ewald SE, Mouchess ML, Barton GM, Nucleic acid recognition by the innate immune system., 2011; Annual review of immunology. 29() 185-214 PMID: 21219183 |

Ewald SE, Barton GM, Nucleic acid sensing Toll-like receptors in autoimmunity., 2010; Current opinion in immunology. 23(1) 3-9 PMID: 21146971 | PMCID: PMC3057394

Ewald SE, Lee BL, Lau L, Wickliffe KE, Shi GP, Chapman HA, Barton GM, The ectodomain of Toll-like receptor 9 is cleaved to generate a functional receptor., 2008; Nature. 456(7222) 658-62 PMID: 18820679 | PMCID: PMC2596276