Fowell Receives NIH Grant to Study T Cell Behavior at Cornell University

Deborah Fowell, professor and chair of the Department of Microbiology and Immunology in the College of Veterinary Medicine, has received a five-year, $2.32 million MERIT award from the National Institutes of Health (NIH) to fund research into the factors that help guide immune cells toward specific tissues.

The MERIT (Method for Extending Research in Time) award goes to a highly selective cohort of researchers with “stellar records of research accomplishment,” according to the NIH. The award – which has no application process and for which researchers are nominated directly by the NIH – can be extended for up to five years without a competitive peer-review process.

“It’s incredibly liberating to be able to follow our ideas through to completion with the security of long-term funding,” Fowell said.

Fowell’s work focuses on T cells, white blood cells that form part of the immune system. Over the last several years, therapeutic strategies using T cells have been a new weapon in the fight against cancer. While these therapies are highly promising, they are currently inefficient. Learning more about how T cells are guided through the body will allow researchers to design the next generation of T cell therapies, which will hopefully be far more effective against not only cancer but autoimmune diseases and fibrosis.

During a course of T cell cancer therapy, a patient’s T cells are genetically altered in a laboratory to give them the ability to attack cancer cells. These new, cancer-targeting cells are cultivated and reintroduced into the patient’s body. But the modified cells are alarmingly bad at homing in on their tumor targets. “Only about 10% of the T cells actually get to the target organ,” Fowell said. “The system is incredibly inefficient.”

One of the reasons for this inefficiency, according to Fowell, has to do with a lack of knowledge about the interactions between T cells and chemokines, small proteins that serve as T cells’ guidance system, shepherding them where they are most needed.

“By studying how these guidance cues work, we’ll be able to better engineer the next generation of T cell therapies so that we increase efficiency,” Fowell said.

To shed light on how chemokines work, Fowell is using techniques that allow her to visualize the immune system in real time, in living tissues, via multiphoton microscopy, a technology first developed at Cornell by biological imaging pioneer Watt Webb. She will also employ new optogenetics techniques, in which millisecond-length flashes of light are used to mark T cells in time and space.

“We can identify cells in one location and fluorescently mark them, just by shining light, and then ask: How does inflammation, or a tumor, change their location?” Fowell said. “We can look at them moving within the tissues and from one location to another.”

Fowell and her team have already discovered that T cells respond to the chemokines differently over the course of a disease.

“You might find that, at an early stage of disease, be that cancer or autoimmunity, the T cells have a different set of guidance cues compared with a later stage of disease,” she said. “Different guidance systems are used in different locations too; a tumor in the skin versus the lung, for instance.”