From Molecules to Medicines: RNA Research Drives Drug Discovery at the Hargrove Lab
As a Canada Research Chair and the director of the Centre for Medicinal Chemistry (CMC), Amanda Hargrove is leading a team on the front lines of drug discovery, developing RNA-targeted therapies for diseases ranging from cancer to viral infections. Professor Hargrove is based in the Department of Chemical and Physical Sciences (CPS) at the University of Toronto Mississauga (UTM) and also holds an appointment in the Department of Chemistry at the St. George campus.
A physical organic chemist by training, Hargrove spent more than a decade at Duke University studying how small molecules interact with RNA — a molecule once thought to be a simple messenger between DNA and proteins — before moving her lab to UTM in 2024. Today, scientists know RNA regulates nearly every biological process, not only in humans but across all domains of life.
Despite this, most drugs still target proteins. In fact, 95 percent of small-molecule therapeutics focus on proteins, leaving RNA largely unexplored. “Maybe the reason we haven't found cures for diseases like cancer is that we’ve only looked at proteins,” Hargrove says. “It’s not that we’ve been looking at the wrong things — but there’s an ‘and’ that we haven’t considered.”
She argues RNA is that missing piece. At the Hargrove Lab, they're designing small molecules that bind to RNA directly and change its behaviour, unlocking new possibilities for treating diseases such as cancer, neurodegenerative diseases, and viral infections.
Initially focused on non-coding RNAs linked to metastatic cancer, the lab expanded into targeting viral RNA, whose structures are better characterized. The team now works on two fronts: cancer therapeutics and RNA-targeted antivirals, combining computational modelling, chemical synthesis, and biological assays. Working with biophysicists, molecular biologists, and virologists, they've identified small molecules with antiviral activity against Enterovirus 71 — the cause of Hand, Foot, and Mouth Disease — as well as SARS-CoV-2 and other coronaviruses.
Maybe the reason we haven't found cures for diseases like cancer is that we’ve only looked at proteins. It’s not that we’ve been looking at the wrong things — but there’s an ‘and’ that we haven’t considered.
Scaling this work meant finding an institution that specialized in both drug discovery and biophysical chemistry. "U of T provided the perfect environment for our next steps," Hargrove says.
The Mississauga campus offers a brand-new Science Building, a strong concentration of biophysics faculty, and the Centre for Medicinal Chemistry, which she now leads. Downtown, the St. George campus contributes its medical research facilities and hospital network. The combination of state-of-the-art facilities and cutting edge research across campuses, along with Canada's investment in research and innovation, enables U of T to support ambitious work and attract top scientific talent.
The decision made, the hard part was moving the Hargrove Lab across borders, which involved transporting specialized equipment, chemicals, and years of accumulated research. The transition was eased by three graduate students who relocated with her from Duke.
“They were instrumental in setting up the lab,” Hargrove says, “and, importantly, they brought along some of the lab culture.”
That culture is built on collaboration and mentorship: every new member is paired with a lab mentor; weekly meetings keep projects connected; graduate students lead independent research; and undergraduates gain hands-on experience in synthesis, biochemistry, and cell biology. It's a community, she says, that pairs scientific independence with mutual support.
With the lab fully operational and new collaborations underway, Hargrove's looking ahead. The team continues to expand with trainees, and partnerships across U of T are opening doors to ambitious projects. “It was a whirlwind first year,” she admits, “but everyone at UTM, particularly the CPS department, was incredibly helpful and supportive.”
Hargrove is also thinking beyond her own lab. As CMC director, she's helping shape an interdisciplinary hub designed to accelerate the pharmaceutical industry in Canada by pushing into new territory in the treatment of aggressive and currently untreatable diseases.
The CMC will help move fundamental discoveries along the drug development pathway, training the next generation of researchers while supporting new intellectual property, attracting investment in technology and talent, and giving researchers access to hands-on resources and expertise — including a state-of-the-art core facility opening this fall.
“Our vision is that the CMC will fill a key gap in the drug discovery pathway,” Hargrove says, “for researchers at U of T and across Mississauga. There are a lot of good things coming.”
