A new technique for spatial mapping of cells can help detect, fight cancer

A new innovation award for proposals from UChicago Pritzker School of Molecular Engineering faculty will help advance a new technique of mapping human tissue, one with impressive implications for detecting and fighting cancer.

PME Asst. Prof. Nicolas Chevrier received the first-ever Lavichant Faculty Innovation Award. The award reviews proposals by PME faculty for both technical merit as well as the likelihood that the work is on a path toward practical commercial development.  

Chevrier’s proposal involved spatially resolved transcriptomics (ST), a burgeoning field of mapping molecules and cells from tissue samples like biopsies. Chevrier has developed a new ST platform, one that initial testing indicates can map much larger tissue samples at much higher resolution than otherwise available.

“It can help basic and translational cancer research by reaching a better understanding of how cancer progresses and responds to drugs, inform clinical decisions, and find new therapy ideas to test,” Chevrier said.

In initial testing, Chevrier’s platform – Array-seq – showed an eightfold increase in resolution, a twofold to threefold increase in sensitivity, a 25-fold increase in the surface area capable of being studied and a one-hundredfold decrease in cost compared to the most common commercial ST platform.

PME Director of Development and Associate Dean of Alumni Relations & Development Heather Upshaw said the interdisciplinary nature of Chevrier’s proposal, collaborating with UChicago Medicine and the Biological Sciences Division, helped put it over the top.

“This project is exemplary of the reasons that the University chose to establish PME,” Upshaw said. “UChicago has a long history in the biological sciences and a world-class medical research system through our hospitals. By adding engineering to the mix, we are able to leverage these resources and translate them through to transformative impact.”

Combining the workhorses

The field of spatially resolved transcriptomics (ST) has emerged over the past half a decade. Researchers use this technology to build a map in space of cell types and molecules across tissues sections.

To develop Array-seq, Chevrier and colleagues combined the two main workhorses in gene expression from the beginning of the 21st century – DNA microarrays and next-generation sequencing. By combining those two technologies, the team was able to create a simple, large-format platform for ST profiling that can analyze much larger samples at much higher resolution than previously possible.

Array-seq developed out of Chevrier’s immunology work. He wanted a more comprehensive report than previously available of how the immune system behaves in the context of disease.

“That's what motivated us to develop a tool that would allow us to create a spatial molecular profile of a whole mouse,” Chevrier said. “Imagine you induce a disease in mice that impacts many organs. You can now section the whole animal and measure mRNA molecules in space across all tissues and cell types of the body at once.”

Most research in this area studies how a particular type of cell in one tissue type reacts to a particular stimulus – for example, how a skin cell reacts to a flu shot. Chevrier needed to get a more encompassing view and, to obtain that, invented Array-seq.

“That was the initial motivation, but now we have this platform that's very flexible and large format, we can dream of many more things to do with it,” Chevrier said. “For example, we hope to make an impact on our understanding of human diseases. Typically, people rely on small biopsies to investigate tissue processes in humans. Here, thanks to the scale of the measurements which we can do, we can ask questions at the level of an entire organ.”

The Lavichant Award will fund the project’s next steps, using colorectal cancer samples from UChicago Medicine’s Human Tissue Resource Center to further test Array-seq, providing proof of concept for this new technology.

“This is just a starting point,” Chevrier said.