John Hickey: When It Comes to Studying Cells, Location is Everything

John Hickey will join the faculty of Duke University’s Department of Biomedical Engineering, beginning January 1, 2024. By developing new technologies to study how and where cells are organized within tissues, Hickey will explore how cells coordinate and respond to their environment in both healthy and diseased states. With this knowledge, Hickey hopes to develop new biomaterials and cellular therapies to correct and control cellular function and tissue structure.

The structure of an organ is similar to a Lego set. Individual pieces can be combined to form a specific segment, like the wheels or wings of a plane. Each segment has its own function, and they are combined into a functional, final structure. In biology, individual cells coordinate to form different types of tissues, like vasculature or connective tissues, which are combined to create the organs that enable life.

“But nature didn’t provide a Lego manual to biology,” says Hickey. “We don’t always know how or why cells coordinate to create healthy tissue, or what happens when things go haywire.”

Currently the American Chemical Society Postdoctoral Fellow in Garry Nolan’s lab at Stanford University, Hickey specializes in spatial biology, where he uses a combination of computational and imaging tools to examine and map the interactions of cells within larger tissue samples.

On the imaging front, Hickey relies on a technique known as multiplex imaging, which allows researchers to attach color-coded antibodies to the surface proteins on cells. Because different types of cells will express different surface proteins, researchers are left with a colorful––and informative–– image of tissue. Once this is complete, Hickey deploys machine learning algorithms and other computational tools to identify the types of cells present in the tissue sample and map their spatial proximity to each other.

“It’s like you’re looking at a map and you can zoom out in range from county to state to nation. The same concept is possible with the human body,” says Hickey. “This approach gives us the spatial locations of single cells, but we can also see the larger cellular neighborhoods in the tissue to see how and where different cell types are grouped and study how they interact.”

Hickey has applied these techniques across a wide array of tissues and disease conditions,

In one example, recently highlighted in Nature, Hickey explored the organization of the healthy human intestine and identified several unique cellular neighborhoods within the intestine. Hickey examined how different cell groups could interact on a molecular level, and his team was able to study how the behavior of the two cell groups helped organize the intestinal tissue.

“Finding distinct organizations across organs and disease states implies a distinct set of ‘rules’ that we hope to start to understand in greater detail that govern the formation of these larger multicellular structures,” says Hickey.

In his role at Duke, Hickey will continue to advance these techniques to explore both basic and complex questions about how specific cells may coordinate and support functions within healthy tissue. He will also investigate how these signals and cellular structures break down in diseases like cancer, autoimmune disorders or even during aging.

“One of the things I’m particularly passionate about is cell therapy, so I plan to explore how to make cell therapies better for solid tumor cancers,” says Hickey. “This research will hopefully allow us to identify interactions or behaviors that cause things to go wrong, which gives us a target for biomaterials and other cellular therapies.”

Although Hickey will be the first researcher in Duke BME to specialize in spatial biology, his work will complement the efforts of several faculty who specialize in drug and gene delivery methods, including Pranam Chatterjee, Charles Gersbach and Michael Lynch. He also looks forward to working with researchers in Duke BME’s long-standing biomaterials program, including Tatiana Segura, Sharon Gerecht and Joel Collier.

“The collaborative spirit of the department and the caliber of the professors and students of the department was especially attractive to me,” says Hickey. “I could see a vision of myself in the department, having a successful lab and being able to do the type of research I wanted because of the people that were around me to support my work.”