Dr. Deborah Fowell, professor and chair of the Department of Microbiology and Immunology, has received a five-year MERIT award from the National Institutes of Health (NIH). This prestigious and highly selective award, valued at $2.32 million, will fund an investigation, using cutting-edge imaging tools, into the factors that help guide immune cells towards specific tissues.

The MERIT award, which stands for “Method for Extending Research In Time,” is given to a highly selective cohort of researchers with “stellar records of research accomplishment.” It is a five-year award, and can be extended for up to another five years without having to go through a competitive peer-review process. “I’m very honored,” said Fowell. “This will allow me to develop a research program with longevity.”

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. 

During a course 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 ten percent of the T cells actually get to the target organ,” said Fowell. “The system is incredibly inefficient.”

One of the reasons for this inefficiency, according to Fowell, has to do with our lack of knowledge about the interactions between T cells and small proteins called chemokines. Chemokines are the T cells’ guidance system, shepherding them to where they are most needed, “to the right place at the right time,” said Fowell. But we don’t know much about how they function. “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.”

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, using multiphoton microscopy, a technology first developed at Cornell by biological imaging pioneer Dr. 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? We can look at them moving within the tissues and from one location to another,” Fowell said.

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,” said Fowell. “Different guidance systems are used in different locations too, a tumor in the skin versus the lung, for instance.”

The MERIT award, for which there is no application process and for which exceptional researchers can only be nominated by the NIH, will allow Fowell to understand these cues, which could unlock more effective T cell therapies, not just for cancer, but also for other illnesses too, including autoimmune diseases and fibrosis. “It’s incredibly liberating,” said Fowell, “to be able to follow our ideas through to completion with the security of long-term funding.”

Written by Tomas Weber