Susan C. Baker, Ph.D
Ph.D., Vanderbilt University
Major Research Interests: The focus of my research is to study how viruses replicate and cause disease. We are interested in identifying and characterizing viral proteins that modulate the host response to infection. We have identified several viral proteins that antagonize the innate immune response, particularly the interferon response, which is critical for controlling disease.
We study the expression, proteolytic processing and function of the coronavirus RNA polymerase polyprotein. This complex polyprotein holds the key to understanding how coronavirus replication is regulated. We found that the polyprotein is processed into 16 products by viral proteases. Many of the replicase proteins are multifunctional and function to inhibit the innate immune response. We are investigating the mechanism used by viral proteins to inhibit the innate immune response. We also target viral interferon antagonists for inactivation to determine if these modified viruses can be used as live, attenuated vaccines for existing and emerging coronaviruses.
We also study the etiology and pathogenesis of Kawasaki Disease (KD). KD is the leading cause of acquired heart disease in children in developed nations, but the cause of KD is unknown. Using KD-specific antibodies, we showed that an antigen is found in both the coronary arteries and in bronchial epithelial cells of KD patients, suggesting a respiratory portal of entry for the KD agent. We collaborate with Infectious Disease expert Dr. Anne Rowley for these studies.
Mielech, Anna M., X. Deng, Y. Chen, E. Kindler, D.L. Wheeler, A.D. Mesecar, V. Thiel, S. Perlman and Susan C. Baker. (2015). Murine coronavirus ubiquitin-like domain is important for papain-like protease stability and viral pathogenesis. J. Virol. 89: 4907-4917. Selected by the editors for the “Spotlight.”
Rowley, Anne H., Wylie, Kristine M., Kim, Kwang-Youn A., Pink, Adam J., Yang, Amy, Reindel, Rebecca, Baker, Susan C., Shulman, Stanford T., Orenstein, Jan M., Lingen, Mark W., Weinstock, George M., Wylie, Todd N. (2015). The transcriptional profile of coronary arteritis in Kawasaki Disease. BMC Genomics 2015; 16:1076. PMCID: PMC4683744.
Clasman, J.R., Baez-Santos, Y.M., Mettelman, R.C., O’Brien, A., Baker, Susan C. and A.D. Mesecar. (2017). X-ray structure and enzymatic activity profile of a core papain-like protease of MERS Coronavirus with utility for Structure-based Drug Design. Nature Scientific Reports 7, 40292; doi: 10.1038/srep40292.
Rowley, A.H., Baker, S.C., Kim, K.A., Shulman, S.T., Yang, A., Arrollo, D., DeBerge, M., Han, S., Sibinga, N.E.S., Pink, A.J., and E.B. Thorp. (2017). Allograft Inflammatory Factor-1 links T cell activation, interferon response, and macrophage activation in chronic Kawasaki Disease arteritis. Journal of the Pediatric Infectious Disease Society. 15 May 2017.
Deng, X., A. Mielech, M. Hackbart, R. Mettelman, A. O’Brien, G. Yi, C. C. Kao and Susan C. Baker. (2017). Coronavirus Nonstructural Protein 15 Mediates Evasion of dsRNA Sensors and Limits Apoptosis in Macrophages. Proc. Natl. Acad. Sci. doi 10.1073/pnas.1618310114.
O’Brien, A., R.C. Mettelman, A. Volk, N.M. Andre, G.R. Whittaker, Susan C. Baker. (2018). Characterizing replication kinetics and plaque production of type I feline infectious peritonitis virus in three feline cell lines. Virology 525: 1-9. PMC6483087
Niemeyer, Daniela, Kirstin Mösbauer, Eva M. Klein, Andrea Sieberg, Robert C. Mettelman, Anna M. Mielech, Ronald Dijkman, Susan C. Baker, Christian Drosten, Marcel A. Müller (2018). The papain-like protease determines a virulence trait that varies among members of the SARS-coronavirus species. PLoS Pathog 14(9): e1007296.
Deng, Xufang, Robert C. Mettelman, Amornrat O’Brien, and Susan C. Baker (2019). Analysis of coronavirus temperature-sensitive mutants reveals an interplay between the macrodomain and papain-like protease impacting replication and pathogenesis. JVI.02140-18. doi: 10.1128/JVI.02140-18.
Deng, Xufang, A. vanGeelen, A.C. Buckley, K.M. Lager, K.S. Faaberg, and Susan C. Baker. (2019). Coronavirus endoribonuclease activity in porcine epidemic diarrhea virus suppresses type I and type III interferon responses. J Virol 93:e02000-18. https://doi.org/ 10.1128/JVI.02000-18.