Carlos Hernandez-Rodriguez

(2020-2022)

Trainee in the Bagaitkar Lab

My research focus on understanding how bacterial pathogens manipulate immune response in the oral cavity. Specifically, we determined whether the keystone periodontal pathogen Porphyromonas gingivalis (Pg) influenced IFN production and anti-viral immunity in gingival epithelial cells (GECs) and oral keratinocytes. My preliminary data show that P. gingivalis shuts down inducible and constitute interferon (IFN) pathways making the oral epithelium susceptible to viral infection. My ongoing work will delineate the molecular mechanisms by which P. gingivalis blocks interferons and enhances susceptibility to pathogenic and oncogenic viruses, which can cause oral squamous cell carcinomas (OSCC).

Amanda Brady 

(2021-2023)

Trainee in the Lawrenz Lab

My research is focused on understanding the mechanisms in which Yersinia pestis, the bacterial agent that causes the disease known as plague, subverts the immune response to generate a non-inflammatory environment required for acute infection. Lipid mediators are critical signaling molecules produced by the host to mount a rapid and protective immune response. Of these lipids, leukotriene B4 (LTB4) is a potent inducer of inflammation normally produced during infection. My lab recently discovered that Y. pestis prevents the synthesis of LTB4 by human neutrophils, suggesting that the lack of LTB4 synthesis by neutrophils, and potentially by other host cells, is a major contributor to the non-inflammatory response associated with plague. To test this hypothesis, I am using a combination of animal and cell culture models to define the LTB4 response of immune cells to Y. pestis and the consequences of Y. pestis mediated inhibition of LTB4 synthesis on interactions between leukocytes and Y. pestis. Defining how Y. pestis manipulates the synthesis of LTB4 will not only provide a better understanding of plague but will also provide better insight into LTB4 signaling in the context of other LTB4-mediated diseases.

Caleb S. Whitley

(2021-2023)

Trainee in the Mitchell Lab

 My research focuses on the interplay between vaccine reactogenicity (i.e. local and systemic adverse events) and immunogenicity, which are two measurable outcomes following immunization. It remains unclear if local and systemic adverse events can be uncoupled from positive immunization outcomes. My work primarily involves two studies; First, understanding which inflammatory pathways are or are not needed for immunogenicity and second, investigating the mechanism(s) of successful adjuvantation exemplified by MPL Adjuvant™. I am currently working on human cell responses to MPL stimulation while developing a rabbit immunization model of reactogenicity in the presence of a prostaglandin synthesis inhibitor or histamine receptor antagonist.

Morgan Duff

(2018-19)

Trainee in the Schmidt Lab

Sarah L. Price

(2019-2020)

Trainee in Lawrenz Lab

My research focus is to identify a novel zinc acquisition system inYersinia pestis and study how the system is involved in plague pathogenesis. Previous work has revealed that Yersiniabactin, a well-established iron siderophore, plays a role in zinc acquisition as well. Currently, I have demonstrated that the Yersiniabactin system contributes to virulence independent of iron acquisition by using a novel hemochromatosis mouse model. Furthermore, I have shown that the Yersiniabactin system allows Y. pestisto better compete for zinc with the host zinc sequestration molecule calprotectin. Finally, I plan to use a variation of Tn-seq, called droplet Tn-seq, to identify genes required for growth in Zinc-limited conditions.

Andrew M. Skidmore

(2019-2021)

Trainee in Chung Lab

My research focuses on the characterization of the mechanism of action of antiviral compounds and how their targets function during infection. I am currently utilizing previously developed compounds that inhibit the replication of Venezuelan Equine Encephalitis virus to characterize the target regions of the viral nonstructural proteins 2 and 4. These regions appear to be novel targets for antivirals against alphaviruses, as they have not been previously implicated in viral replication. In addition, the target regions show clade-specific diversity among alphaviruses, implying an importance in alphavirus evolution and pathogenesis.

Autumn T. LaPointe

(2018-2020)

Trainee in the Sokoloski Lab

V "Trey" D. Landers III

(2019-2021)

Trainee in the Sokoloski Lab

Ben Charpentier

(2020-2021)

 Trainee under Shirish Barve and Scott Whittemore 

Alcohol induced pathogenic changes in the gut-liver-brain axis: relevance to neuroinflammation and neuronal injury

My project supported by the T32 will explore the direct role of the microbiome in the development of alcohol induced neuroinflammation as well as the combinatorial effects with ethanol consumption. Our work has determined that patients with alcohol use disorders have pathogenic changes in the gut microbiome characterized by a loss of butyrate producing bacteria. We have generated gut-humanized mice by subjecting conventional mice to fecal microbiota transplantation (FMT) from alcoholic hepatitis (AH) patients (or controls) from a well phenotyped cohort. Using this innovative mouse model that recapitulates several important clinical features associated with AH, we are examining the impact of alcohol on the gut-liver-brain axis and development of neuro-inflammation and injury.  Our initial findings have identified for the first-time functional changes in neurons in response to both FMT and ethanol consumption.  We will use the funding opportunity to investigate the ethanol-driven pathogenic mechanisms leading to neuro-inflammation and neuronal injury employing well-established animal models of chronic ethanol consumption. Our previous work has identified that phosphodiesterase 4B (PDE4B) is a critical mediator of ethanol induced neuroinflammation.  Through the use of PDE4B chimeric animals, paired with the FMT model, we will determine if neuro-pathogenesis is mediated through systemic inflammation or is directly affected by local (brain) PDE4B activation.  Through these experiments we expect to advance the field by determining the pathogenic role of gut microbial dysbiosis and consequent PDE4B expression in the development of ethanol induced neuroinflammation and injury.  

Professor PD/PI

Molecular biology of T Cells in infection and autoimmunity.