Source: http://molecularbiosciences.ku.edu/susan-m-egan
Timestamp: 2019-04-24 10:24:09+00:00

Document:
Susan Egan earned a B. S. in biology from Rensselaer Polytechnic Institute (1984), a PhD in microbiology from Cornell University (1991), and was a postdoctoral fellow in the lab of Dr. Robert Schleif at the Johns Hopkins University. She began her faculty position at the University of Kansas in 1994, initially in the Department of Microbiology, and following the merger of several departments, in the current Department of Molecular Biosciences. She is also an affiliate member of the Center for Computational Biology. Dr. Egan was promoted to Professor in 2009. She served as Associate Chair of Molecular Biosciences from 2008 through 2012, and currently serve as departmental Chairperson (since 2014). Research in the Egan lab focuses on the mechanisms used by bacterial transcriptional activator proteins to increase expression of specific genes under appropriate environmental conditions. Understanding these mechanisms is critical to the goal of targeting activators of virulence factor expression in bacterial pathogens as a method to prevent or ameliorate disease. Indeed, the lab has published a number of studies toward this goal. The Egan lab uses a variety of techniques including genetics, biochemistry, protein structure determination, protein-DNA interaction, and computational methods.
Regulation of bacterial transcription, Development of novel anti-bacterial agents.
My primary research interest is understanding the regulation of gene expression (especially positive regulation) at a molecular level. In our lab we examine the molecular biology of gene regulation in E. coli, with a focus on the L-rhamnose catabolic genes, and the fact that the L-rhamnose regulator genes are members of the AraC family of regulatory proteins. Many AraC family proteins are regulators of virulence factors in bacterial pathogens, therefore, we use the L-rhamnose regulators as models to understand the function of proteins in this family. Our ultimate goal is to identify small molecules that block the function of AraC family proteins and have potential as anti-bacterial agents.
The widespread availability of antibiotics since the 1940’s has dramatically reduced the number of deaths due to bacterial infections, however we are rapidly losing our advantage over our bacterial foes as antibiotic resistance becomes increasingly prevalent. We must investigate novel targets for antibacterial agents to avoid the return of commonplace deaths due to bacterial infections. Many members of the very large AraC/XylS family of transcription activators are required for the expression of virulence factors in bacterial pathogens. In several cases it has been shown that deletion of an AraC/XylS activator drastically reduces pathogenesis, indicating that members of this family have potential as targets for antibacterial agents. Our long-term goal is to identify small molecule inhibitors of AraC/XylS family activators. Towards this goal, we are currently working on two fronts. First, we are performing a screen of a large library of small molecules for ones that specifically inhibit the activity of the AraC/XylS family protein RhaS. Once we identify compounds that are inhibitory, we will investigate their mechanism of action. Towards this end, we are also investigating the mechanisms used by the AraC/XylS family protein RhaS that underlie its ability to activate transcription of the appropriate genes and under the appropriate conditions. Once we have identified the mechanisms of a few more of RhaS’s functions, we will be in an excellent position to identify the mechanisms of action of inhibitory small molecules. Ultimately, we will screen for inhibitors of AraC/XylS family activators of virulence factors in bacterial pathogens. We expect that these inhibitors have potential to be developed into novel strategies for treatment of bacterial diseases.
We have already obtained a substantial amount of information about RhaS function. For example, we have identified four amino acid residues in RhaS that make base-specific contacts with its DNA-binding site, and further, have identified the base-pairs in the DNA that each of these residues contacts. This allows us to unequivocally orient each monomer of the RhaS dimer on its DNA site. We have also identified two amino acid residues in RhaS that are directly required to contact RNA polymerase to activate transcription. In addition, we have identified the amino acid residues in the sigma70 subunit of RNA polymerase that each of these RhaS residues contacts. There are only very few transcription activators for which interactions with RNA polymerase have been defined at this level of detail. We are currently investigating the mechanisms by which RhaS: dimerizes; binds its ligand, L-rhamnose; and transmits the information that L-rhamnose is or is not available from its N-terminal ligand binding and dimerization domain to its C-terminal DNA-binding and transcription activation domain.
Wickstrum, J. R., Skredenske, J. M., Balasubramaniam, V. Jones, K. & Egan, S. M. (2010). The AraC/XylS Family Activator RhaS Negatively Autoregulates rhaSR Expression by Preventing Cyclic AMP Receptor Protein Activation. Journal of Bacteriology, 192(1), 225-232.
Kolin, A. Balasubramaniam, V. Skredenske, J. M., Wickstrum, J. R., & Egan, S. M. (2008). Differences in the Mechanism of the Allosteric L-Rhamnose Responses of the AraC/XylS Family Transcription Activators RhaS and RhaR. Molecular Microbiology, 68(2), 448-461.
Tungtur, S. Egan, S. M., & Swint-Kruse, L. (2007). Functional consequences of exchanging domains between LacI and PurR are mediated by the intervening linker sequence. Proteins: Structure, Function, and Bioinformatics, 68(1), 375-388.
Wickstrum, J. R., Skredenske, J. M., Kolin, A. Jin, D. J., Fang, J. & Egan, S. M. (2007). Transcription Activation by the DNA-Binding Domain of the AraC Family Protein RhaS in the Absence of its Effector-Binding Domain. Journal of Bacteriology, 189(14), 4984-4993.
Kolin, A. Jevtic, V. Swint-Kruse, L. & Egan, S. M. (2007). Linker regions of the RhaS and RhaR proteins. Journal of Bacteriology, 189(1), 269-271.
Wickstrum, J. R., Santangelo, T. J., & Egan, S. M. (2005). Cyclic AMP receptor protein and RhaR synergistically activate transcription from the L-Rhamnose-responsive rhaSR promoter in Escherichia coli. Journal of Bacteriology, 187(19), 6708-6718.
Wickstrum, J. R., & Egan, S. M. (2004). Amino acid contacts between Sigma 70 domain 4 and the transcription activators RhaS and RhaR. Journal of Bacteriology, 186(18), 6277-6285.
Suppes, G. J., Egan, S. Casillan, A. J., Chan, K. W., & Seckar, B. (2003). Impact of high pressure freezing on DH5 alpha Escherichia coli and red blood cells. Cryobiology, 47(2), 93-101.
Egan, S. M. (2002). Growing Repertoire of AraC/XylS Activators. Journal of Bacteriology, 184(20), 5529-5532.
Wickstrum, J. R., & Egan, S. M. (2002). Ni+-affinity purification of untagged cyclic AMP receptor protein. BioTechniques, 33(4), 728-730.
Ruiz, R. Ramos, J. L., & Egan, S. M. (2001). Interactions of the XylS regulators with the C-terminal domain of the RNA polymerase α subunit influence the expression level from the cognate Pm promoter. FEBS Letters, 491, 207-211.
Bhende, P. M., & Egan, S. M. (2000). Genetic evidence that transcription activation by RhaS involves specific amino acid contacts with sigma70. Journal of Bacteriology, 182(17), 4959-4969.
Holcroft, C. C., & Egan, S. M. (2000). Interdependence of activation at rhaSR by cyclic AMP receptor protein, the RNA polymerase alpha subunit C-terminal domain and RhaR. Journal of Bacteriology, 182(23), 6774-6782.
Holcroft, C. C., & Egan, S. M. (2000). Roles of cyclic AMP receptor protein and the carboxyl-terminal domain of the α subunit in transcription activation of the Escherichia coli rhaBAD operon. Journal of Bacteriology, 182(12), 3529-3535.
Egan, S. M., Pease, A. J., Lang, J. Li, X. Rao, V. Gillette, W. K., Ruiz, R. Ramos, J. L., & Wolf, R. E. (2000). Transcription activation by a variety of AraC/XylS family activators does not depend on the class-II-specific activation determinant in the N-terminal domain of the RNA polymerase alpha subunit. Journal of Bacteriology, 182(24), 7075-7077.
Bhende, P. M., & Egan, S. M. (1999). Amino acid-DNA contacts by RhaS: an AraC family transcription activator. Journal of Bacteriology, 181(17), 5185-5192.
Egan, S. M., & Schlief, R. F. (1994). DNA dependent renaturation of an insoluble DNA binding protein: Identification of the RhaS binding site at rhaBAD. Journal of Molecular Biology, 243, 821-829.
Egan, S. M., & Schlief, R. F. (1993). A regulatory cascade in the induction of rhaBAD. Journal of Molecular Biology, 234, 87-98.
Morajelo, P. Egan, S. M., Hidalgo, E. & Aguilar, J. (1993). Sequencing and characterization of a gene cluster encoding the enzymes for L-rhamnose metabolism in Escherichia coli. Journal of Bacteriology, 175(17), 5585-5594.
Collins, L. A., Egan, S. M., & Stewart, V. (1992). Mutational analysis reveals functional similarity between NARX, a nitrate sensor in Escherichia coli K-12, and the methyl-accepting chemotaxis proteins. Journal of Bacteriology, 174(11), 3667-3675.
Egan, S. M., & Stewart, V. (1991). Mutational analysis of nitrate regulatory gene narL in Escherichia coli K-12. Journal of Bacteriology, 173(14), 4424-4432.
Egan, S. M., & Stewart, V. (1990). Nitrate regulation of anaerobic respiratory gene expression in narX deletion mutants of Escherichia coli K-12. Journal of Bacteriology, 172(9), 5020-5029.
Search PubMed for articles by Susan M. Egan.

References: V. 
 V. 
 V. 
 V. 
 V. 
 V. 
 V.