Major Areas of Research
- Pathogenesis of emerging viruses that cause severe respiratory disease
- Develop in vitro and in vivo model systems to integrate analyses of pathogen, single cell, and host to identify common pathways involved in disease progression
- Use our knowledge of the pathogenesis of respiratory tract infections to aid development of effective, broad-acting therapeutics
Lower respiratory tract infections are the leading cause of infectious disease deaths worldwide, and the fifth most important cause of death overall. Respiratory viruses keep emerging at a steady pace (e.g. MERS-CoV, enterovirus D68, avian influenza viruses), adding to the burden of respiratory tract infections on global health. Major advances have been made in our knowledge of the pathogenic processes involved in severe respiratory disease over the past decade; however, few successful treatments have made their way into the clinic. A key problem in the development of treatments for severe respiratory virus infections is that virus replication often peaks ahead of disease severity. Rather than virus-induced lung damage alone, the proinflammatory immune response also contributes to severe respiratory disease. Although increasing attention is given to the host processes involved in severe respiratory infections, these studies are often hampered by a focus on in vivo pathogenesis in lethal disease models, or on mechanistic studies of single molecules or signaling pathways in vitro. In my lab, we aim to combine pathogenesis studies with detailed molecular analyses to identify molecular determinants of severe respiratory tract disease within the virus and the host. Ultimately, the identification of common pathways involved in lower respiratory tract disease progression and druggable targets within those pathways will be used to develop broad-acting, syndrome-based therapeutics.
Dr. de Wit received her Ph.D. in virology in 2006 from Erasmus University Rotterdam, the Netherlands. Her research there focused on the replication, pathogenesis and transmission of influenza A virus. In 2009, Dr. de Wit moved to the Laboratory of Virology of NIAID in Hamilton, Montana to work in the biosafety level 4 laboratory there. Here, she focused on the pathogenesis of and countermeasures against Nipah virus, the Middle East Respiratory Syndrome Coronavirus and the 1918 H1N1 influenza A virus (Spanish flu). In 2014-2015, Dr. de Wit spent 4 months in a field lab in Monrovia, Liberia in charge of patient diagnostics for several Ebola Treatment Units in the area, to help contain the devastating Ebola epidemic in Liberia. Currently, Dr. de Wit’s research aims to combine pathogenesis studies with detailed molecular analyses to identify molecular determinants of severe respiratory tract disease within the virus and the host.
Brandi McCoy Williamson, M.P.H., Microbiologist
Lizette Pérez-Pérez, MSc, Postbac IRTA
Reinaldo Mercado-Hernandez, B.Sc., Postbaccalaureate IRTA
- de Wit E, van Doremalen N, Falzarano D, Munster VJ. SARS and MERS: recent insights into emerging coronaviruses. Nat Rev Micro. 2016. doi: 10.1038/nrmicro.2016.81. PubMed PMID: 27344959.
- Baseler L, Scott DP, Saturday G, Horne E, Rosenke R, Thomas T, Meade-White K, Haddock E, Feldmann H, de Wit E. Identifying early target cells of Nipah virus infection in Syrian hamsters. PLoS NTD. 2016. doi: 10.1371/journal.pntd.0005120. PubMed PMID: 27812087.
- Rosenke K, Adjemian J, Munster VJ, Marzi A, Falzarano D, Onyango CO, Ochieng M, Juma B, Fischer RJ, Prescott JB, Safronetz D, Omballa V, Owuor C, Hoenen T, Groseth A, Martellaro C, van Doremalen N, Zemtsova G, Self J, Bushmaker T, McNally K, Rowe T, Emery SL, Feldmann F, Williamson BN, Best SM, Nyenswah TG, Grolla A, Strong JE, Kobinger G, Bolay FK, Zoon KC, Stassijns J, Giuliani R, de Smet M, Nichol ST, Fields B, Sprecher A, Massaquoi M, Feldmann H, de Wit E. Plasmodium parasitemia associated with increased survival in Ebola virus-infected patients. Clin Infect Dis. 2016. doi: 10.1093/cid/ciw452. PubMed PMID: 27531847.
- de Wit E, Siegers JY, Cronin JM, Weatherman S, van den Brand JM, Leijten LM, van Run P, Begeman L, van den Ham HJ, Andeweg AC, Bushmaker T, Scott DP, Saturday G, Munster VJ, Feldmann H, van Riel D. 1918 H1N1 influenza virus replicates and induces proinflammatory cytokine responses in extrarespiratory tissues of ferrets. J Infect Dis. 2018. doi: 10.1093/infdis/jiy003. PubMed PMID: 29329410.
- Lo MK, Feldmann F, Gary JM, Jordan R, Bannister R, Cronin J, Patel NR, Klena JD, Nichol ST, Cihlar T, Zaki SR, Feldmann H, Spiropoulou CF, de Wit E.. Remdesivir (GS-5734) protects African green monkeys from Nipah virus challenge.Sci Transl Med. 2019. doi: 10.1126/scitranslmed.aau9242. PubMed PMID: 31142680
- Munster VJ, Koopmans M, van Doremalen N, van Riel D, de Wit E. A Novel Coronavirus Emerging in China - Key Questions for Impact Assessment. New Engl J Med. 2020. DOI: 10.1056/NEJMp2000929. PubMed PMID: 31978293