Susan C. Baker, Ph.D
Professor

Ph.D., Vanderbilt University

Molecular Virologist

The molecular biology and pathogenesis of coronaviruses
The etiology and pathogenesis of Kawasaki Disease

Baker Lab Home Page

 
Coronaviruses 

The focus of my research is to study how viruses replicate and cause disease. One major area of our research is to investigate the replication of coronaviruses, including the coronavirus that caused the outbreak of Severe Acute Respiratory Syndrome (SARS). 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. Viral proteases are attractive targets for antiviral drug development. Our research efforts are evaluating protease inhibitors as antiviral drugs and determining if viral proteases block the innate immune response to facilitate viral replication. 

Kawasaki Disease

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, my collaborator Dr. Anne Rowley 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 are using human airway epithelial cell cultures to identify and propagate microbes associated with KD.  We also exploit PCR arrays to profile gene expression in KD lung and coronary artery tissue to investigate mechanisms of pathogenesis. 

Selected Publications

de Groot, Raoul, J., Susan C. Baker, Ralph S. Baric, Caroline S. Brown, Christian Drosten, Luis Enjuanes, Ron A.M. Fouchier, Monica Galiano, Alexander E. Gorbalenya, Ziad Memish, Stanley Perlman, Leo L.M. Poon, Eric J. Snijder, Gwen M. Stephens4 Patrick C.Y. Woo, Ali M. Zaki, Maria Zambon, John Ziebuhr (2013).  Middle East Respiratory Syndrome Coronavirus (MERS-CoV):  Announcement of the Coronavirus Study Group. J. Virol. 87, 7790-7792.

Xing, Yaling, Jianfei Chen, Jian Tu, Bailing Zhang, Xiaojuan Chen, Hongyan Shi, Susan C. Baker, Li Feng, and Zhongbin Chen.  2013.  The papain-like protease of porcine epidemic diarrhea virus negatively regulates type I interferon pathway by acting as a viral deubiquitinase.  Journal of General Virology 94, 1554-1567.

Jacobs, Jon, Valerie Grum-Tokars, Ya Zhou, Mark Turlington, S. Adrian Saldanha, Peter Chase, Aimee Eggler, Eric S. Dawson, Yahira M. Baez-Santos, Sakshi Tomar, Anna M. Mielech, Susan C. Baker, Craig W. Lindsley, Peter Hodder, Andrew Mesecar, and Shaun R. Stauffer. 2013.  Discovery, Synthesis, And Structure-Based Optimization of a Series of N-(tert-Butyl)-2-(N-arylamido)-2-(pyridin-3-yl) Acetamides (ML188) as Potent Noncovalent Small Molecule Inhibitors of the Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) 3CL Protease.  Journal of Medicinal Chemistry 56 (2), 534-546. PMCID: PMC3569073

Beachboard, D.C., X. Lu, S.C. Baker, and M.R. Denison. 2013. Murine hepatitis virus nsp4 N258T mutants are not temperature-sensitive. Virology 435: 210-213.

Reindel, R., Susan C. Baker, Kwang-Youn Kim, Carol Rowley, Stanford Shulman, Jan Orenstein, Elizabeth Perlman, Mark Lingen, and Anne Rowley.  2013.  Integrins Alpha4 and Alpha M, Collagen1A1, and Matrix Metalloproteinase 7 Are Upregulated in Acute Kawasaki Disease Vasculopathy.  Pediatric Research doi: 10.1038/pr2012.185.

Orenstein, J. M., S. T. Shulman, L. M. Fox, S. C. Baker, T. R. Bhatti, P. A. Russo, J.  P. De Chadarevian, E. J. Perlman, C. Trevenen, M. Takahashi, G. Mierau, M. B. Kalelkar, A. Rotta, and A. H. Rowley.  2012. Three Vasculopathic Processes Characterize Kawasaki Disease:  A Light and Transmission Electron Microscopic Study.  PLoS One 7:e38998.

Elshabrawy, H.A., Melissa M. Coughlin, Susan C. Baker, Bellur S. Prabhakar. 2012.  Human Monoclonal Antibodies against Highly Conserved HR1 and HR2 Domains of the SARS-CoV Spike Protein Are More Broadly Neutralizing. Research Article | published 21 Nov 2012 | PLOS ONE 10.1371/journal.pone.0050366

Sun, L., Y. Yang, X. Chen, Y. Xing, D. B. Nichols, M. A. Clementz, B. S. Banach, K. Li, S. C. Baker, Z. Chen. 2012. Coronavirus papain-like proteases negatively regulate the innate immune response through disruption of STING-mediated signaling. PLoS ONE 7(2): e30802.

Zust, R., L. Cervantes-Barragan, M. Habjan, R. Maier, B. W. Neuman, J. Ziebuhr, S. C. Baker, W. Barchet, S. G. Siddell, B. Ludewig, V. Thiel. 2011. Ribose 2′-O-methylation provides a molecular signature for MDA5-mediated distinction of self and non-self mRNA.  Nature Immunology, 12, 137-147.

Stokes, H.L., S. Baliji, C.G. Hui, S.G. Sawicki, S.C. Baker and S.G. Siddell.  (2010).  A New Cistron in the Murine Hepatitis Virus Replicase Gene.  J. Virol. Epub online 28 July 2010.

Rowley, A. H., S. C. Baker, S. T. Shulman, K. H. Rand, M. S. Tretiakova, E. J. Perlman, F. L. Garcia, N. F. Tajuddin, L. M. Fox, J. H. Huang, J. C. Ralphe, K. Takahashi, J. Flatow, S. Lin, M. B. Kalelkar, B. Soriano, J. M. Orenstein. 2011. Ultrastructural, immunofluorescence, and RNA evidence support the hypothesis of a "new" virus associated with Kawasaki Disease. Journal of Infectious Diseases 203, 1021-1030.

Ghosh AK, Takayama J, Rao KV, Ratia K, Chaudhuri R, Mulhearn DC, Lee H, Nichols DB, Baliji S, Baker SC, Johnson ME, Mesecar AD. Severe acute respiratory syndrome coronavirus papain-like novel protease inhibitors: design, synthesis, protein-ligand X-ray structure and biological evaluation.J Med Chem. 2010 Jul 8;53(13):4968-79.

Clementz MA, Chen Z, Banach BS, Wang Y, Sun L, Ratia K, Baez-Santos YM, Wang J, Takayama J, Ghosh AK, Li K, Mesecar AD, Baker SC. Deubiquitinating and interferon antagonism activities of coronavirus papain-like proteases. J Virol. 2010 May;84(9):4619-29. Epub 2010 Feb 24.

Ghosh AK, Takayama J, Aubin Y, Ratia K, Chaudhuri R, Baez Y, Sleeman K, Coughlin M, Nichols DB, Mulhearn DC, Prabhakar BS, Baker SC, Johnson ME, Mesecar AD.Structure-based design, synthesis, and biological evaluation of a series of novel and reversible inhibitors for the severe acute respiratory syndrome-coronavirus papain-like protease. J Med Chem. 2009 Aug 27;52(16):5228-40.

Baliji S, Cammer SA, Sobral B, Baker SC. (2009). Detection of nonstructural protein 6 in murine coronavirus-infected cells and analysis of the transmembrane topology by using bioinformatics and molecular approaches. J Virol. 83(13):6957-62. Epub 2009 Apr 22.PMID: 19386712.

S Banach B, Orenstein JM, Fox LM, Randell SH, Rowley AH, Baker SC. (2009). Human airway epithelial cell culture to identify new respiratory viruses: coronavirus NL63 as a model. J Virol Methods. 156(1-2):19-26. Epub 2008 Dec 5.PMID: 19027037.

Ratia K, Pegan S, Takayama J, Sleeman K, Coughlin M, Baliji S, Chaudhuri R, Fu W, Prabhakar BS, Johnson ME, Baker SC, Ghosh AK, Mesecar AD. (2008). A noncovalent class of papain-like protease/deubiquitinase inhibitors blocks SARS virus replication. Proc Natl Acad Sci U S A. 105(42):16119-24. Epub 2008 Oct 13.PMID: 18852458.

Ghosh AK, Gong G, Grum-Tokars V, Mulhearn DC, Baker SC, Coughlin M, Prabhakar BS, Sleeman K, Johnson ME, Mesecar AD. (2008). Design, synthesis and antiviral efficacy of a series of potent chloropyridyl ester-derived SARS-CoV 3CLpro inhibitors. Bioorg Med Chem Lett. 18(20):5684-8. Epub 2008 Aug 28.PMID: 18796354.

Baker, S.C. and M. Denison. (2008). Cell biology of nidovirus replication complexes. In"The Nidoviruses," (ed. S. Perlman, T. Gallagher and E.J. Snijder). ASM Press, pp. 103-113.

Baker, S.C. (2008). Coronaviridae: Molecular Biology. In "The Encyclopedia of Virology,"(ed. B. Mahy). Elsevier (in press).

Rowley AH, Baker SC, Orenstein JM, Shulman ST. (2008). Searching for the cause of Kawasaki disease--cytoplasmic inclusion bodies provide new insight. Nat Rev Microbiol. 6(5):394-401.PMID: 18364728.

Bechill J, Chen Z, Brewer JW, Baker SC. (2008). Coronavirus infection modulates the unfolded protein response and mediates sustained translational repression. J Virol. 82(9):4492-501. Epub 2008 Feb 27.PMID: 18305036.

Clementz MA, Kanjanahaluethai A, O'Brien TE, Baker SC. (2008). Mutation in murine coronavirus replication protein nsp4 alters assembly of double membrane vesicles. Virology. 375(1):118-29. Epub 2008 Mar 4.PMID: 18295294.

Rowley AH, Baker SC, Shulman ST, Garcia FL, Fox LM, Kos IM, Crawford SE, Russo PA, Hammadeh R, Takahashi K, Orenstein JM. (2008). RNA-containing cytoplasmic inclusion bodies in ciliated bronchial epithelium months to years after acute Kawasaki disease. PLoS One. 3(2):e1582.PMID: 18270572.

Orenstein JM, Banach B, Baker SC. (2008). Morphogenesis of Coronavirus HCoV-NL63 in Cell Culture: A Transmission Electron Microscopic Study. Open Infect Dis J. 2:52-58.PMID: 19844604.

Ghosh AK, Xi K, Grum-Tokars V, Xu X, Ratia K, Fu W, Houser KV, Baker SC, Johnson ME, Mesecar AD. (2007). Structure-based design, synthesis, and biological evaluation of peptidomimetic SARS-CoV 3CLpro inhibitors. Bioorg Med Chem Lett. 17(21):5876-80. Epub 2007 Aug 19.PMID: 17855091.

Devaraj SG, Wang N, Chen Z, Chen Z, Tseng M, Barretto N, Lin R, Peters CJ, Tseng CT, Baker SC, Li K. (2007). Regulation of IRF-3-dependent innate immunity by the papain-like protease domain of the severe acute respiratory syndrome coronavirus. J Biol Chem. 282(44):32208-21. Epub 2007 Aug 30.PMID: 17761676.

Grum-Tokars V, Ratia K, Begaye A, Baker SC, Mesecar AD. (2008). Evaluating the 3C-like protease activity of SARS-Coronavirus: recommendations for standardized assays for drug discovery. Virus Res. 133(1):63-73. Epub 2007 Mar 29.PMID: 17397958.

Grum-Tokars, V., Ratia,  K., Begaye, A., Baker, S.C., Mesecar AD. (2007). Evaluating the 3C-like protease activity of SARS-Coronavirus: Recommendations for standardized assays for drug discovery. Virus Res. Mar 28; [Epub ahead of print] 

Chen, Z., Wang, Y., Ratia, K., Mesecar, A.D., Wilkinson, K. D., Baker, S.C. (2007). Proteolytic processing and deubiquitinating activity of papain-like proteases of human coronavirus NL63. J. Virol. 81: 6007-18. 

Kanjanahaluethai, A., Chen, Z., Jukneliene, D., Baker, S. C. (2007). Membrane topology of murine coronavirus replicase nonstructural protein 3. Virology 361:391-401.

Snyder, E.E., Kampanya, N, ,et al. PATRIC: the VBI PathoSystems Resource Integration Center. Nucleic Acids Res. (2007) Jan;35(Database issue):D401-6. 

Ratia, K., K.S. Saikatendu, B.D. Santarsiero, N. Barretto, S.C. Baker, R.C. Stevens, and A.D. Mesecar (2006). SARS coronavirus papain-like protease: structure of a viral deubiquitinating enzyme. Proc. Natl. Acad. Sci. 103: 5717-5722.

Ghosh, A. K., K. Xi, K. Ratia, W. Fu, B. H. Harcourt, P. A. Rota, S. C. Baker, M. E. Johnson and A. D. Mesecar (2005). Design and synthesis of peptidomimetic Severe Acute Respiratory Syndrome chymotrypsin-like protease inhibitors. J. Med. Chem. 48: 6767-6771.

Barretto, N., D. Jukneliene, K. Ratia, Z. Chen, A. D. Mesecar and S. C. Baker (2005). The papain-like protease of severe acute respiratory syndrome coronavirus has deubiquitinating activity. J. Virol. 79: 15189-15198 (selected for JVI Spotlight).


Kanjanahaluethai, A., D. Jukneliene, and S. C. Baker (2003). Identification of the murine coronavirus MP1 cleavage site recognized by papain-like proteinase 2. J. Virol. 77: 7376-7382.

Gosert, R., A. Kanjanahaluethai, D. Egger, K. Bienz, and S. C. Baker (2002). RNA replication of mouse hepatitis virus takes place at double-membrane vesicles. J. Virol. 76: 3698-3708.

Kanjanahaluethai, A. and S. C. Baker (2000). "Identification of mouse hepatitis virus papain-like proteinase 2 activity. J Virol 74: 7911-7921.

Search PubMed for a complete listing of Susan Baker's publications.

 

 

 

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