arrow-downCreated with Sketch. icon-story icon-emailCreated with Sketch. icon-linkCreated with Sketch. icon-specializationCreated with Sketch. icon-videoCreated with Sketch. icon__arrow-down--orange icon__download icon__goals icon__institution icon__mission icon__outcomes icon__pathways tooltip-arrowCreated with Sketch.

Friend or Foe?

What can we learn from the "double-edged sword” of our immune system?

kate fitzgeraldWhether the question arises among nation-states or deep within the complex mechanisms of our immune system, the wrong answer can have dire consequences. For the last 15 years, Dr. Kate Fitzgerald’s research has explored how our bodies get it right—our innate immunity to infection and disease. But it’s the “double-edged sword” of our immune system that most defines her work. The same capacity that enables our bodies to recognize and vanquish infection or disease also drives inflammation. And, inflammation is now recognized as a component in a wide variety of diseases.

As a child growing up in Ireland, Dr. Fitzgerald relished the idea of teaching and she would gather her playmates for classroom lessons created in her front yard. Inspired perhaps by her engineer father, she also had an interest in science. This blossomed after high school summers volunteering in a biochemist’s lab at the local hospital. Today, she does both as Professor of Medicine and Director of the Program in Innate Immunity at the University of Massachusetts Medical School. In her role as Principal Investigator at the Fitzgerald Lab, she leads a team of six post-doctoral fellows, five graduate students and two technical staff to investigate the molecular mechanisms controlling the inflammatory response. The lab’s work extends into immunology, biochemistry, molecular biology and genetics to understand these processes.

“How does innate immunity distinguish between what’s dangerous and what’s innocuous? And can we turn it off when those mechanisms fail?”

When Dr. Fitzgerald began her research there, the field of innate immunology was wide open. But swift advances in technology are propelling new research opportunities. As a result, the field is now filling up and becoming much more competitive. She’s also had her share of the sometimes chaotic “higgledy piggledy” of a bustling, multifaceted research lab. But Dr. Fitzgerald credits her progress to time and experience, along with the good fortune of great mentors and advocates. She’s also learned to navigate the complex interplay of science, technology and a working lab by developing rigorous, reproducible systems and gathering a “front yard classroom” of generous team players who complement each other’s strengths and expertise.

A Small Discovery with Big Implications

Even so, the research funded by the Kenneth Rainin Foundation came about almost accidentally, after stumbling on a finding that drew her team into the unexplored science of overlooked molecule(s)—long non-coding RNAs (lncRNAs). Previously, most of biology focused on only two percent of our DNA that leads to the proteins in our bodies. Until recently, the rest was considered “junk” and researchers assumed that these RNA molecules had no biological function in immunology.

“We stumbled on what might be the tip of the iceberg in our understanding and treatment of inflammatory disease.”

What Dr. Fitzgerald discovered, however, is that one of these RNA molecules appears to act as a brake on immune activation. The science has a long way to go before the development of therapeutic applications in combating inflammatory diseases like IBD. But her lab’s findings to date—working on cells in mice and mouse-models of intestinal inflammation—illuminate an enormous potential for using these lncRNA molecules to regulate gene expression during immune cell activation. Her next steps are to understand if their findings in mice have relevance in humans. Specifically, she’ll examine these mechanisms in humans and in particular in IBD patient samples to translate the findings into clinical practice.

The value of Dr. Fitzgerald’s work to the field of innate immunology is both basic and far-reaching. Her lab’s ongoing research is contributing to our fundamental understanding of the inflammatory process. And, this may have a broad range of applications. And breakthrough discoveries like those related to the lncRNA molecule may be the tip of the iceberg in understanding—and treating—infectious, inflammatory and autoimmune disease in humans.

Related Stories