Pathogenesis, therapy and prevention of severe influenza in a nonhuman primate model: We have developed the first reproducible model of severe influenza in macaques by administering highly pathogenic avian influenza virus in the form of small particle aerosols, in collaboration with Doug Reed, PhD, of the Center for Vaccine Research. This work is possible because of the Regional Biocontainment Laboratory, a specialized BSL-3 and ABSL-3 facility. Using this novel and powerful model we are working in three different projects: (1) Defining the innate mechanisms driving severe disease in the lung; (2) Testing novel therapeutic approaches targeting innate immune pathways to prevent severe disease; and (3) Testing the efficacy of universal vaccines and broadly neutralizing antibodies to prevent severe disease.
Dengue virus infection in human skin: Dengue virus is transmitted into skin via the bites of infected mosquitoes, but we do not know how the mosquito interacts with the virus and host to effect transmission and spread within the host. To study this in a relevant translational model we inoculate healthy human skin explants that have been removed from anonymous donors in the course of elective plastic surgery. We are collaborating with a team of vector biologists at the University of Texas Medical Branch to study how infected mosquitoes transmit and spread virus using this model.
SARS-CoV-2 infection and immunology: The lung is the primary target of SARS-CoV-2 in humans, and to study the virus-host interaction in this tissue we have established a model using precision-cut human lung slices from cadavers. We also have collaborative studies with a number of groups to evaluate novel therapies including antibodies for COVID-19.
1984 | Massey University, Palmerston North, New Zealand | Bachelor of Veterinary Science
1993 | University of California, Davis | PhD
1996 | University of Pittsburgh | Postdoc
Co-Director | IDM 2003 | Host Response to Microbial Infection
Wonderlich ER, Swan ZD, Bissel SJ, Hartman AL, Carney JP, O’Malley KJ, Obadan AO, Santos J, Walker R, Sturgeon TJ, Frye LJ Jr., Maiello P, Scanga CA, Bowling JD, Bouwer AL, Duangkhae PA, Wiley CA, Flynn JL, Wang J, Cole KS, Perez DR &Barratt-Boyes SM (2017). Widespread virus replication in alveoli drives acute respiratory distress syndrome in aerosolized H5N1 influenza infection of macaques. J Immunol; 198: 1616-1626.
Duangkhae P, Erdos G, Ryman KD, Watkins SC, Falo LD Jr., Marques ETA Jr. &Barratt-Boyes SM (2018). Interplay between keratinocytes and myeloid cells drives dengue virus spread in human skin. J Invest Dermatol; 138: 618-626.
Wonderlich ER, Caroline AL, McMillen CM, Walters AW, Reed DS,Barratt-Boyes SM & Hartman AL (2018). Peripheral blood biomarkers of disease outcome in a monkey model of Rift Valley fever encephalitis. J Virol; 92: e01662-17
Castanha PMS, Duangkhae D,Erdos G, Watkins SC, Falo LD, Marques ETA,Barratt-Boyes SM (2020). Reciprocal immune enhancement of dengue and Zika virus infection in human skin. JCI Insight; 5(3): e133653
Corry J, Kettenberg G, Upadhyay AA, Wallace M, Marti MM, Wonderlich ER, Bissel SJ, Goss K, Sturgeon TJ, Watkins SC, Reed DS, Bosinger SE,Barratt-Boyes SM (2022). Infiltration of inflammatory macrophages and neutrophils and widespread pyroptosis in lung drive influenza lethality in nonhuman primates. PLoS Pathogens; 18(3): e1010395. PMCID: PMC8939778
Castanha PMS, Tuttle DJ, Kitsios GD, Jacobs JL, Brago-Neto U, Duespohl M, Rathod S, Marti MM, Wheeler S, Naqvi A, Staines B, Mellors J, Morris A, McVerry BJ, Shah F, Schaefer C, Macatangay BJC, Methe B, Fernandez CA,Barratt-Boyes SM, Burke DS, Marques ETA (2022). IgG response to SARS-CoV-2 and seasonal coronaviruses contributes to complement overactivation in severe COVID-19 patients. J Inf Dis; Published online 2022 March 10. Doi: 10.1093/infdis/jiac091.