Wednesday, January 20, 2016
Jenna McCracken successfully defended her PhD thesis, "Neutrophil Cell Death in F. tularensis Infection" on Tuesday, January 19, 2016. Jenna is pictured with her mentor, Dr. Lee-Ann Allen.
The human immune system defends the body against infection and is comprised of multiple cell types including neutrophils and macrophages. Neutrophils are recruited to sites of inflammation where they rapidly ingest and degrade invading microbes. To prevent the spread of infection, neutrophils die via apoptosis and are cleared by macrophages. The bacterium Francisella tularensiscauses the life-threatening disease tularemia, which is characterized by the deleterious accumulation of neutrophils in the lungs. It is well-established that Francisella evades neutrophil antimicrobial defenses and resides within the host cell cytosol, and our lab recently discovered that this bacterium extends neutrophil lifespan to preserve its replicative niche.
The goal of these studies is to determine the molecular mechanisms by which F. tularensis prevents neutrophil death and to explore the fate of infected neutrophils following engulfment by macrophages. We report that this microbe alters the critical balance of pro-death and pro-survival factors via changes in protein abundance, activity, and subcellular location. We also demonstrate that infected cells are resistant to treatment with R-roscovitine, a cell death-inducing drug currently in testing for the treatment of inflammation. Furthermore, we show that macrophages readily consume infected neutrophils, resulting in both the release of their infectious cargo into the macrophage cytoplasm as well as substantial bacterial replication. Our data begin to define molecular mechanisms to account for the profound accumulation of neutrophils and tissue damage that occurs during tularemia.
About Jenna
Jenna was born and raised in Belmont, CA, in the San Francisco Bay Area. At an early age, her curiosity and desire to understand how things work manifested itself in scientific topics. Her father, a veterinary pharmacologist, encouraged her inquisitiveness and supplied her with endless insights into the world of biology. As a young child, when she asked why adults consume coffee in the morning, her father quickly drew up the chemical structure of caffeine on the back of a napkin and explained how neurotransmitters and receptors worked. Jenna constantly asked questions of her mother, an anthropologist, such as “Why did dinosaurs go extinct?” or “How many bones do I have?” thus entailing numerous trips to the library or a bookstore.
Jenna’s fascination turned to bacteria during college at UCLA, where she graduated summa cum laude with a B.S. in Microbiology, Immunology, and Molecular Genetics. Jenna’s first research experience was a summer internship at Genentech where she studied microbial pathogenesis with a focus on Mycobacterium marinum. This exposure to research was pivotal in shaping her future career goals, as she attained insight into how research can be used to study clinical problems. Upon her return to college, she began a year-long research project in which she developed novel protocols to isolate and characterize bacteriophage from environmental samples, culminating in the development of course material for an undergraduate microbiology lab course, wherein she worked alongside her advising professor to teach the new curriculum. After graduation, she spent an additional year at UCLA researching the molecular structure of proteins in Salmonella.
Her enthusiasm for the scientific process led her to pursue dual MD/PhD degrees at The University of Iowa. Jenna joined the Allen lab to complete her thesis work in 2011 and sought to advance the understanding of neutrophil cell death and its contribution to tularemia pathogenesis. She had the opportunity to present her research at the Gordon Research Conference on Phagocytes and the annual meeting of the Society for Leukocyte Biology. Consistent with her interest in disease at molecular and cellular levels, she plans to pursue residency training in pathology upon completion of medical school. Outside of the lab, you can find Jenna experimenting in the kitchen and planning her next travel adventure.