Hickey Receives NSF CAREER Award to Study How Environmental Factors Drive Cellular Behavior

John Hickey, assistant professor of biomedical engineering at Duke University, has been awarded a National Science Foundation Faculty Early Career Development (CAREER) Award.

The competitive five-year, $570,000 grant for outstanding young faculty will support Hickey’s research as he develops new methods to study how cells in the same environment coordinate and develop into different states.   

Hickey’s lab explores how cells coordinate and respond to their environment in both healthy and diseased states. This work relies on a technique known as multiplex imaging, which enables viewing dozens of different proteins on cells at once. Because different cell types will express different surface proteins, Hickey and his team can create colorful images of cells and tissues that relate to their state and function.

With this award, Hickey will use these techniques to better understand how factors in the cell’s environment can influence the state of individual cells. The team hopes to use this knowledge to better control cell fate for cell therapies—with future cell engineering applications including stem cell therapies, tissue regeneration, and biopharmaceutical production.

“If we take a set of cells that are in the same starting state, throw them into a culture dish and add a stimulus, theoretically if the nutrients and environment is the same then the cellular characteristics should be consistent,” said Hickey. “But that’s not what we see. Instead, we see a lot of different states of cells emerge by the end, and we don’t know what influences these cellular changes.”

According to Hickey, one area where this has been a problem is in the development of T cell therapies, which involve collecting immune cells from the body and engineering them to target and destroy cancer cells. Certain types of T cells are more therapeutically effective, but because scientists cannot standardize the development of these cells, production is inefficient.

“It’s not ideal when you’re creating a clinical product,” said Hickey. “But the field hasn’t yet addressed what drives the heterogeneity that we see in T cell development.”

Hickey hopes that his project can begin to change that.

First, the team will use biomaterials to create artificial cells that can mimic the functions of natural cells. These artificial cells will be coated with different proteins before being added to a culture alongside standardized T cells. Using live video microscopy, the team will then track the cellular growth and behavior over days. Once the video is collected, they will use their advanced imaging paired with machine learning to identify the different states of T cells that developed.

“We’ll use these technologies to draw a connection between T cell behavior and their resulting states and functions,” explained Hickey. “We’ll be able to see what cells the T cells interacted with and measure how long these interactions occurred to draw connections about how they influenced their development.”

The team hopes they can use this data to show how applying certain stimuli to a cell can lead to certain states, allowing them to optimize cellular engineering. Eventually, Hickey said, this work could also lead to clinical studies to explore what T cell characteristics are the most efficient at destroying tumor cells.

The team will also advance tools for citizen scientists by leveraging the visual and computational tools the team will be using throughout their project. To facilitate this, Hickey launched a partnership with Manu Prakash, an associate professor of bioengineering at Stanford University. Prakash developed Foldoscope, a low-cost microscope made of paper intended to make microscopy more accessible for people around the world. Using a simplified version of their software, Hickey and his team will create tutorials to show Foldoscope users how they can collect and analyze their own imaging data from these microscopes for basic purposes.

“This grant allows us to use these advanced tools to answer a basic question about cells’ behavior that will impact society broadly at both therapeutic and industrial research applications involving the complex machines that are cells,” said Hickey. “I’m incredibly grateful for the opportunity and support as we pursue this exciting work.”