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Shames Lab

Contact information

Division of Biology
Kansas State University
347 Ackert Hall (office)
331 Ackert Hall (lab)
1717 Claflin Road
Manhattan, KS 66506

(785) 532-0110 (office)
(785) 532-0131 (lab)
sshames@ksu.edu 

Research

Host response to intracellular pathogens

As accidental pathogens of humans, Legionella species are an excellent tool to investigate the mammalian innate immune response to bacterial pathogens.  The study of Legionella restriction by the mammalian immune system has led to multiple breakthroughs, including the detection of bacterial flagellin by the NAIP5/NLRC4 inflammasome. A major component of research in our lab is to understand how effector proteins contribute to bacterial clearance by healthy hosts.  Effector translocation by the Dot/Icm secretion system is required for bacterial replication but also contributes to immune clearance of Legionella by a process termed 'Effector-Triggered Immunity'.   An excellent example of this enhanced pro-inflammatory gene expression in macrophages resulting from effector-mediated inhibition of host cell protein translation by several L. pneumophila effectors.  Our lab is working on characterizing effectors that enhance immune recognition of Legionella species within metazoans.  This work will reveal mechanisms of pathogen detection and host defense in addition to providing avenues for therapeutics against a range of pathogens. 

Temporal regulation of L. pneumophila egress and host cell viability

Temporal regulation of egress from host cells is pivotal to the virulence strategy of intracellular pathogens since they are dependent on the host cell to replicate.  For L. pneumophila, host cell death prior to differentiation into the transmissive phase is detrimental to the pathogen.  Thus, L. pneumophila preserves the host cell until the opportune stage in its lifecycle.  However,  mechanisms used by L. pneumophila to regulate host cell cytotoxicity, especially at late stages of infection, are largely unknown. To gain insight into this critical aspect of the L. pneumophila lifecycle, we are using high-throughput sequencing techniques to conduct forward genetic screens to identify and characterize genes that contribute to host cell lysis and bacterial egress. This approach will lead to the identification of genes used by L. pneumophila to control host cell viability such that bacterial egress occurs when it is most beneficial for the pathogen. We're working to gain insight into mechanisms by which (1) bacterial virulence factors can thwart normal host cell death pathways; and (2) cell autonomous responses of host cells that promote cell death. Further characterization of identified genes will enable dissection of host cell signaling pathways manipulated by bacterial pathogens to preserve their replicative niche.