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Samantha Krysa

Mentor: Mary Wilson, M.D.
Lab Room: 500J EMRB
Lab Phone: 319-335-4315

Francisella tularensis-mediated delay of apoptosis in human neutrophils

F. tularensis is a Gram-negative, facultative intracellular organism and the etiologic agent of the disease tularemia. F. tularensis infects many cell types, including polymorphonuclear leukocytes (PMNs; neutrophils). The most abundant leukocyte in circulation, neutrophils are a vital component of the innate immune system and the first line of defense at sites of infection. Neutrophils are inherently short-lived cells that undergo constitutive, spontaneous apoptosis 24 hours after entering circulation. This tightly-regulated, timely apoptosis is crucial for neutrophils to effectively curtail infections and resolve inflammation. Our lab recently demonstrated that F. tularensis prolongs human neutrophil lifespan by inhibiting all major apoptotic pathways. We have also shown that direct contact between F. tularensis and neutrophils is not essential for the prolonged survival of infected neutrophils suggesting that a secreted bacterial protein may contribute to this effect. In addition, our lab has also shown that F. tularensis infection of neutrophils causes a vast increase in expression of glycolytic enzymes, indicating that modulation of metabolism and extension of lifespan may be mechanistically-linked. However, all of the factors that function to prolong neutrophil lifespan, and the mechanisms by which these factors are interfering with the major apoptosis pathways in neutrophils remain undefined.

The primary goal of my research is to identify the factor(s) that contribute to prolonging human neutrophil lifespan following F. tularensis infection and further elucidate the mechanism by which this prolongation occurs. This will provide a broader understanding of the mechanisms by which F. tularensis manipulates the host immune response to cause disease.

Honors and Awards

  • 2018 Molecular Medicine retreat poster award/travel grant
  • Travel Award 2019 Society for Leukocyte Biology
  • Graduate College Post-Comprehensive Research Fellowship - Spring 2020