Leslie Dan Faculty of Pharmacy cancer researcher leads $1.2 million NIH grant to uncover drug targets

Shana Kelley receives new grant for development of cell screening technology, with Stéphane Angers and Jason Moffat

A team of researchers led by Shana Kelley, University Professor at the Leslie Dan Faculty of Pharmacy (LDFP), has received $1.2 million over five years from the U.S. National Institutes of Health to advance new cell screening and sorting technology.

Stéphane Angers, LDFP Professor and Associate Dean of Research, and Jason Moffat, Professor at the Donnelly Centre for Cellular and Biomolecular Research, are working with Kelley on the technology that will help uncover potential new drug targets for cancer.

Immune cells target and destroy abnormal cells, but cancer cells can often hide from the immune system and continue to proliferate. Cancer immunotherapies interact with proteins and signalling pathways in cancer cells to make them “visible” to the immune system again.

“By focusing on cancer and the ways that tumours evade the immune system, we hope to uncover new druggable targets in cells that could be the basis for development of new therapeutics,” said Kelley. “We also aim for new insights about the interactions between the immune system and tumours.”

A technique called CRISPR-Cas9 allows researchers to study the genome by editing out a specific gene in large numbers of cells and examining the effects, including which cells live or die.

But in recent years, researchers have developed “phenotype-based screens” that use the same workflow as a traditional CRISPR screen to look for a specific trait, or how those genes are expressed. This screening system may be a valuable tool for identifying potential drug targets, especially for cancer immunotherapies.

For example, Kelley’s team has previously used phenotypic screens to sort 100 million cells in about an hour, to focus only on cells that overexpress a specific protein that tricks the immune system into leaving a tumour cell alone.

While the technology has potential to uncover new drug targets, it is more challenging to use than traditional CRISPR and thus isn’t commonly used in research labs yet.

With the new NIH funding, Kelley and her collaborators will further develop the phenotypic screening technology to accelerate its use in finding new drug targets, especially for cancer. They are specifically examining two signalling pathways in cancer to look for potential drug targets.

Kelley says that collaboration is critical for the project, which requires a wide range of expertise. “Jason Moffat is a leading expert on the CRISPR Cas9 screening technology, and Stéphane Angers is a signal transduction expert with significant expertise related to cancer biology,” she said. “Together, we can exploit phenotypic screening technology to develop new drugs for cancer.”

“We are really delighted about the funding that the US National Institutes of Health will provide for this project,” Kelley added. “This is a highly multidisciplinary project that would be difficult to fund through existing programs in Canada.”

The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.