Lynn Hancock

Lynn Hancock
  • Associate Professor
  • Undergraduate Coordinator


My primary research interest is in understanding how Enterococcus faecalis, a gut commensal and opportunistic pathogen, adapts its gene expression in order to successfully colonize mammalian hosts at both commensal sites in the intestine, as well as extraintestinal sites where it is frequently associated with infections, including urinary tract infection, bacteremia, wound infection and endocarditis. I have examined a number of bacterial factors associated with successful adaptation to host environments, including resistance to host immune responses including anti-phagocytic capsular polysaccharides, a broadly active cytolytic toxin, secreted proteases and their role in biofilm formation, as well as factors governing lysozyme resistance.  More recently, my lab has explored how enterococci regulate nutritional acquisition systems to take advantage of host components, including commonly available sugars as well as host glycoproteins. To explore these topics, we have also examined the role of two-component signal transduction systems in E. faecalis biology, including the quorum response Fsr system Enterococcus faecalis, as well alternative sigma factors SigV and RpoN.   By focusing on the environments likely encountered in a mammalian host where enterococci colonize and cause infection, we aim to identify factors critical to successful colonization and infection.

I earned my PhD in 2001 under the mentorship of Dr. Michael Gilmore at the University of Oklahoma Health Sciences Center and pursued post-doctoral studies with Dr. James Hoch and Dr. Marta Perego at the Scripps Research Institute.  In 2004, I began a faculty position at Kansas State University before transitioning to the University of Kansas in 2013.

I am currently an Associate Professor in the Department of Molecular Biosciences, am currently the Director of Undergraduate Studies in MB, and am an affiliate of the NIH-sponsored Chemical Biology of Infection Disease CoBRE and serve as Core Leader of the Infectious Disease Assay Development Core


Postdoc (Microbial Signal Transduction), The Scripps Research Institute, 2004
Ph.D. in Microbiology & Immunology, University of Oklahoma Health Sciences Ctr., 2001
M.S. in Microbiology & Immunology, University of Oklahoma Health Sciences Ctr., 1995
B.S. in Molecular Biology (Microbiology), Brigham Young University, 1993


Mechanisms of pathogenesis for Enterococcus

My research laboratory is interested in understanding the mechanisms of pathogenesis for the opportunistic bacterial pathogen, Enterococcus faecalis.  This organism now ranks as a leading cause of hospital acquired infection, causing a variety of infections ranging from urinary tract infection, bacteremia and wound infection to life threatening endocarditis.  To better understand what makes E. faecalis a successful opportunist, we have focused our efforts in understanding microbial factors that contribute to overcoming innate barrier defenses, including an anti-phagocytic response governed by capsular polysaccharides, as well as disruption of complement signaling molecules through the action of a secreted protease (GelE), and the role that gelatinase plays in quorum-dependent biofilm formation.  We have also examined the role of two-component signal transduction networks in allowing E. faecalis to adapt to a variety of cellular stresses, including antibiotics.  We have also explored the role of the SigV regulon in adapting to lysozyme stress, as well as microbial components that contribute to SigV activation.  We have also examined the role of a family of transcription factors, referred to as the RRNPP family, that contribute to bacterial conjugation as well as biofilm-related processes in E. faecalis.  We also discovered a novel ABC-transporter, termed PptAB, conserved in Gram-positive bacteria responsible for secretion of small peptide pheromones.  We are currently exploring the role of the alternative sigma factor RpoN (σ54) in utilizing a variety of carbon sources, many of which are present in host environments.  We are also focused on understanding the signaling networks and microbial factors that contribute to secondary carbon metabolism including utilization of host glycans derived from N-linked glycoproteins.

Identification and characterization of the Enterococcus faecalis capsule genes

As a graduate student, I identified a polysaccharide biosynthetic locus that is present in a subset of E. faecalis isolates and was later shown to be enriched in clinical isolates, where it functions as a polysaccharide capsule. The capsule operon is comprised of either 8 or 9 genes depending on the capsule serotype, with the cpsF gene  product accounting for serologic differences between the two known capsule serotypes. Further work in my own research laboratory demonstrated a role for the capsule in protection from phagocyte clearance by host immune cells (macrophages and neutrophils) by blocking the deposition of complement in the absence of capsule specific antibodies.

Identification and characterization of two-component signal transduction systems in E. faecalis

During my post-doctoral studies, I identified and examined the contribution of 18 TCS systems in E. faecalis strain V583 to antibiotic resistance and biofilm formation. We were the first to show that the Fsr quorum-sensing system contributes to biofilm development through the directed regulation of the secreted protease, gelatinase. We also showed that gelatinase activation proceeds through a novel autocatalytic cleavage at both the amino and carboxy ends of the protein.

Cellular responses leading to biofilm formation and immune evasion in E. faecalis

My laboratory has been interested in understanding how E. faecalis establishes biofilms and how regulatory networks control the timing of events related to the accretion of biofilms. We were the first to show that biofilm development in E. faecalis requires extracellular DNA (eDNA) as an early matrix component and that early E. faecalis biofilms could be disrupted by DNAse treatment. The lytic events leading to this eDNA release were shown to be dependent on the concerted proteolytic action of two Fsr-regulated proteases, gelatinase and serine protease, on the major autolysin AtlA, a cell wall muramidase. This activity we termed fratricide, as only a fraction of cells within the population were shown to be lysed, but that such lysis required active gelatinase activity and intact AtlA. The role of the serine protease counters the pro-lytic events mediated by gelatinase in that it confers a conformation to AtlA that does not result in cell wall cleavage and lysis. Additionally, we were the first to definitively show using isogenic mutants that gelatinase plays a major role in the pathogenesis of endocarditis caused by E. faecalis. Further, we showed that gelatinase exhibited an important role as an immunomodulator by cleaving complement component C5a, which was also shown to effectively reduce the host immune response to the bacterial vegetation on the heart valve.

Cell-cell signaling networks in E. faecalis

More recently, my laboratory has begun pursuing additional signaling networks that contribute to genetic exchange via conjugation, biofilm development and host immune evasion. We were the first to discover how peptide pheromones are ultimately secreted in E. faecalis giving rise to gene transfer events between plasmid donors and recipients. We showed that in addition to the membrane proteases, Lsp and Eep, that a broadly conserved, membrane protein transporter of the EcsAB family (PptAB) was responsible for this activity. The disruption of this protein transporter resulted in significant reductions (5 orders of magnitude) in pheromone-mediated conjugal transfer events. Furthermore, this transporter also significantly contributes to biofilm formation through an unidentified mechanism. The inability to secrete pheromones was also shown to play an important role in an unusual interaction between the first documented vancomycin-resistant isolate, strain V583 and commensal enterococci. Through a collaboration with Michael Gilmore’s laboratory, we showed that strain V583 is inhibited by the specific pheromone, cOB1, secreted by commensal strains. Strain V583 has accrued a number of mobile genetic elements over its evolutionary lifetime, but the consequence of these events has made it more labile to interactions with other commensal E. faecalis strains. In addition to roles in peptide pheromone production, we have also explored the role of Eep and PptAB in regulated intramembrane proteolysis (RIP). In this pathway, Eep activity is required to cleave the anti-sigma factor, RsiV, responsible for sequestering the alternate sigma factor, SigV, at the membrane. SigV is required for resistance to lysozyme, and is released from RsiV by proteolytic cleavage in the presence of lysozyme. A mutant of PptAB is also sensitive to lysozyme, and this appears to be due to its effects on Eep function in the membrane. We have also explored the contribution of RRNPP homologues encoded on the chromosome of E. faecalis that affect biofilm formation and UTI pathogenesis.

Carbon catabolism and its influence on host-adaptation for nutrient acquisition by E. faecalis

In an effort to understand carbon metabolism inE. faecalis, we have focused on the alternative sigma factor, σ54 (RpoN). Transcriptomics of this mutant as well as growth studies in chemically defined media showed that RpoN controlled the primary import of glucose and mannose through a dedicated PTS system.

Deletion of rpoN, resulted in a growth defect with glucose as the sole carbon source, but not in rich media. We observed that the glucose phenotype resulted in derepression of carbon catabolism through CcpA. Three GH18 family glycosyl hydrolases fall under CcpA control and contribute to nutrient acquisition on high-mannose N-linked glycoproteins, deglycosylation of complex type N-linked glycoproteins including IgG, as well as chitolytic activity.  Ongoing work in the laboratory is focused on understanding the regulatory factors that contribute to utilization of these secondary carbon sources abundantly present in host environments, as well as the additional carbon sources controlled by RpoN and associated enhancer binding proteins and the sugar PTS systems they regulate.


  • BIOL 401 -  Honors section, Fundamentals of Microbiology (Fall)
  • BIOL 506 -  Bacterial Infectious Diseases (Spring)
  • BIOL 807 -  Graduate Molecular Biosciences (Fall)

My classroom teaching has encompassed a range of courses in the discipline of Microbiology.  I teach the honors section of Fundamentals of Microbiology in the fall, and a senior level course covering Bacterial Infectious Diseases in the spring.  I also assist in team-teaching the introductory graduate course for Molecular Biosciences graduate students.  I have also recently taught the Advanced Immunology graduate course (BIOL 811, spring 2023) and provide guest lectures in BIOL 812 (Mechanisms of Host-Pathogen Interactions) and BIOL 817 (Research Ethics).

Beyond my formal classroom instruction, I mentor undergraduate and graduate students involved in my research team.  I have the privilege of working with talented and motivated students seeking to hone their research skills and develop as independent, critically-thinking scientists.

Selected Publications

Complete List of Published Works by Lynn E. Hancock:

  1. Keffeler EC, Parthasarathy S, Abdullahi ZA and Hancock LE. 2021. Metabolism of poly-β1,4- N-acetylglucosamine substrates and importation of N-acetylglucosamine and glucosamine by Enterococcus faecalis. J Bacteriol. 2021 Oct 12;203(21):e0037121. doi: 10.1128/JB.00371-21. Epub 2021 Aug 23. PMCID: PMC8508097

  2. Keffeler EC, Iyer VS, Henderson AJ, Huck IL, Schwarting N, Cortez A, Hancock LE. 2021. Activity of CcpA-regulated GH18 family glycosyl hydrolases that contribute to nutrient acquisition and fitness in Enterococcus faecalis. Infect Immun. 2021 Oct 15;89(11):e0034321. doi: 10.1128/IAI.00343-21. Epub 2021 Aug 23. PMCID: PMC8519268

  3. Keffeler EC, Iyer VS, Parthasarathy S, Ramsey MM, Gorman MJ, Barke TL, Varahan S, Olson S, Gilmore MS, Abdullahi ZH, Hancock EN, Hancock LE. 2021. Influence of the alternative sigma factor RpoN on global gene expression and carbon catabolism in Enterococcus faecalis V583. mBio May 18;12(3):e00380-21. doi: 10.1128/mBio.00380-21. PMCID: PMC8262876

  4. Parthasarathy S, Wang X, Carr KR, Varahan S, Hancock EB and Hancock LE. 2021. SigV mediates lysozyme resistance in Enterococcus faecalis via RsiV and PgdA. J Bacteriol. 2021 Sep 23;203(20):e0025821. doi: 10.1128/JB.00258-21. Epub 2021 Aug 9. PMCID: PMC8459761

  5. Parthasarathy S, Jordan LD, Schwarting N, Woods MA, Abdullahi Z, Varahan S, Passos PMS, Miller B, Hancock LE. 2020. Involvement of chromosomally encoded homologs of the RRNPP protein family in Enterococcus faecalis biofilm formation and UTI pathogenesis. J Bacteriol. Jun 15;JB.00063-20. doi: 10.1128/JB.00063-20. Online ahead of print. PMCID: PMC7417834

  6. Gilmore MS, Rauch M, Ramsey MM, Himes PR, Varahan S, Manson JM, Lebreton F, Hancock LE. 2015. Pheromone killing of multidrug-resistant Enterococcus faecalis V583 by native commensal strains. Proc Natl Acad Sci U S A.112(23):7273-8. PMCID: PMC26039987

  7. Varahan S, Harms N, Gilmore MS, Tomich JM, Hancock LE. 2014. An ABC transporter is required for secretion of peptide sex pheromones in Enterococcus faecalis. MBio. Sep 3;5(5):e01726-14. PMCID: PMC25249282

  8. Varahan S, Iyer VS, Moore WT, Hancock LE. 2013. Eep confers lysozyme resistance to Enterococcus faecalis via the activation of the extracytoplasmic function sigma factor SigV. J Bacteriol. 195(14): 3125-34. PMCID: PMC3697634

  9. Iyer VS and Hancock LE. 2012. Deletion of Sigma54 (rpoN) alters the rate of autolysis and biofilm formation in Enterococcus faecalis. J. Bacteriol. 194(2):368-75. PMCID: PMC3256635

  10. Thurlow LR, Thomas VC, Narayan S, Olson S, Fleming SD, Hancock LE. 2010. Gelatinase contributes to the pathogenesis of endocarditis caused by Enterococcus faecalis. Infect Immun. 78(11):4936-43. PMCID: PMC2976315

  11. Thurlow LR, Thomas VC, Hancock LE. 2009. Capsular polysaccharide production in Enterococcus faecalis and the contribution of CpsF to capsule serospecificity. J. Bacteriol. 191(20):6203-10. PMCID: PMC2753019

  12. Thurlow LR, Thomas VC, Fleming SD, Hancock LE. 2009. Enterococcus faecalis capsular polysaccharide serotypes C and D and their contributions to host innate immune evasion. Infect Immun. 77(12):5551-7. PMCID: PMC2786471

  13. Thomas VC, Hiromasa Y, Harms N, Thurlow L, Tomich J, Hancock LE. 2009. A fratricidal mechanism is responsible for eDNA release and biofilm development of Enterococcus faecalis. Mol. Microbiol. 72(4):1022-36. PMCID: PMC2779696

  14. Thomas VC, Thurlow LR, Boyle D, Hancock LE. 2008. Regulation of autolysis-dependent      extracellular DNA release by Enterococcus faecalis extracellular proteases influences biofilm development. J Bacteriol. 190(16):5690-8. doi: 10.1128/JB.00314-08. Epub 2008 Jun 13. PMCID: PMC2519388

  15. Del Papa MF, Hancock LE, Thomas VC, Perego M. 2007. Full activation of Enterococcus faecalis gelatinase by a C-terminal proteolytic cleavage. J Bacteriol. 189(24):8835-43. PMCID: PMC17921295

  16. Hancock LE and Perego M. 2004. Systematic inactivation and phenotypic characterization of two-component signal transduction systems of Enterococcus faecalis V583. J Bacteriol. 186: 7951-7958. PMCID: PMC529088

  17. Hancock LE and Perego M. 2004. The Enterococcus faecalis Fsrtwo-component system controls biofilm development through production of gelatinase. J Bacteriol. 186:5629-5639. PMCID: PMC516840

  18. Hancock LE, Shepard BD, Gilmore MS. 2003. Molecular analysis of the Enterococcus faecalis serotype 2 polysaccharide determinant. J Bacteriol. 185(15):4393-401. PMCID: PMC12867447

  19. Hancock LE and Perego M. 2002. Two-component signal transduction in Enterococcus faecalis. J Bacteriol. 184:5819-5825. PMCID: PMC135378

  20. Hancock LE and Gilmore MS. 2002. The capsular polysaccharide of Enterococcus faecalis and its relationship to other polysaccharides in the cell wall. Proc Natl Acad Sci USA. 99:5474-5479. PMCID: PMC122232