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Few Maps, But Endless Possibilities

Targeting two innate immune sensors to reveal active, dominant viruses in the IBD biome.

Kate Jeffrey, Kenneth Rainin Foundation GranteeBorn and raised outside of Melbourne, Australia, Dr. Kate Jeffrey has traveled far to live, work, and raise a family in Boston. (How far? Just ask her about the snowy winters.) She had no models growing up for a life in scientific research or academia. Her initial intention was to become a doctor, fed by a fundamental desire to cure disease. That impulse was shaped by her mother’s admonition to do what you love to do in order to help people.  

Once at Melbourne University, however, Dr. Jeffrey came to appreciate the creative possibilities of medical research. She found a sense of freedom in the lab and a kinship with artists in the scientific process. The field is inherently nonconformist and researchers pursue their questions with a dogged passion over long periods of time. And by deciphering the intricate puzzles of disease, she could help people—by learning and generating new knowledge. Each turn of her career has served to reinforce that catalyzing idea.

Medical research is an endlessly open landscape, and lab work offers an intellectual and creative freedom matched by very few other professions.

Follow the Trail Where It Takes You 

Dr. Jeffrey completed her doctorate in immunology, working with Professor Charles Mackay at the Garvan Institute of Medical Research in Sydney, Australia. Then, in 2007, she charted a new course for her life in the United States, more than 10,000 miles away from home. 

She landed first in New York where she worked as an immunology editor with Nature Medicine. Discontented in reading about research of others, she returned to the lab and completed her postdoctoral research with Professor Sasha Tarakhovsky at The Rockefeller University. A much shorter jaunt took her further north to Boston. 

Dr. Jeffrey now plies her craft at Massachusetts General Hospital, the original and largest teaching hospital of Harvard Medical School. She established the Jeffrey Lab in 2012, continuing her post-doctoral focus on epigenetic regulation of innate immunity, antiviral defense and inflammation.

Next Stop: The Human Virome 

Then she heard a talk by virologist Herbert W. “Skip” Virgin that dramatically altered the course of her research. He described the mysteries of commensal viruses in our gut. How do they replicate without damaging the host or triggering an immune response?  

Viruses are the most abundant life form on Earth—staggeringly abundant in fact. The largely uncharted enteric virome offered her lab a vast landscape of possibility for Inflammatory Bowel Disease (IBD) research. How do intestinal viruses interact with innate immune sensors? What could that reveal about their disease- or health-driving roles in IBD? Could this lead to creating personalized, virome-focused therapies that reduce, reverse or prevent IBD? The terrain was wide open and tantalizing. 

With more knowledge about the mechanics of the human virome, our development of treatments could advance in leaps and bounds.

Venturing into Uncharted Territory 

But therein lies the challenge. Very little of the viral genome has been sequenced, making it exceedingly difficult to distinguish one virus from another. However, two decades of fast-paced research on commensal bacteria in the human gut have set the medical stage for leveraging that microbiome. And technological advances opened the door to a novel approach for Dr. Jeffrey’s research. 

Using an immunoprecipitation technique called CLIP, Dr. Jeffrey’s lab is targeting two innate immune sensors to reveal active, dominant viruses in the IBD biome. Invented at The Rockefeller University, where Dr. Jeffrey learned the technique, CLIP creates genome-wide maps of host or virus RNA-binding protein interaction sites in living tissue. Dr. Jeffrey’s research also draws on an ensemble of her peers with expertise in colorectal surgery, gastroenterology and computational analysis.

Our next steps are to identify specific viral species that protect or harm (patient well-being/the gut), then leverage that knowledge for IBD therapies.

Leaving Home to Find Home 

Given her professional journey, perhaps Australia figures into the epigenetics of Dr. Jeffrey’s DNA. Australians are enthusiastic international travelers, willing to cover long distances to reach a first destination. And the continent’s far-reaching landscapes get under your skin, boasting large expanses of unexplored territory and remarkable, complex ecosystems. Dr. Jeffrey is clearly comfortable striking off into the Outback of medical research. With advances in science and technology, she also believes that there is no better time for it than now. And perhaps no greater creative calling. 

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