Jessica Lacoste named 2025 Charles H. Best Fellow

The Charles H. Best Postdoctoral Fellowship was established in 2001 as a tribute to Charles H. Best, a celebrated University of Toronto researcher known for discovering insulin alongside Frederick Banting. The award recognizes outstanding postdoctoral fellows at the Donnelly Centre for Cellular and Biomolecular Research who are tackling big questions in biology through systems-thinking.

The 2025 recipient of the Charles H. Best Fellowship is Jessica Lacoste.

Lacoste is a postdoctoral fellow conducting research under the supervision of Peter Roy, professor of molecular genetics and pharmacology and toxicology and Canada Research Chair in Chemical Genetics, Brenda Andrews, university professor of molecular genetics and Canada Research Chair in Systems Genetics & Cell Biology, and Charles Boone, professor of molecular genetics and Banting and Best Distinguished Scholar at U of T.

“On behalf of the Charles H. Best Fellowship selection committee, I congratulate Jessica Lacoste on being selected as the 2025 Best Fellow,” said Stéphane Angers, director of the Donnelly Centre and chair of the Charles H. Best Fellowship selection committee. “Jessica is a tremendous trainee with a great future ahead of her. She is making major contributions to scientific research and community service as the former Vice-President of our Graduate Student Association. Her efforts in systematic biology and drug discovery are addressing the urgent need to find drugs that can treat parasitic and pathogenic infections.”

Lacoste joined the Donnelly Centre as a PhD student after earning a BSc degree in biochemistry from Dalhousie University in Halifax, Nova Scotia. She was encouraged to pursue graduate school through her honours thesis project, which she found to be a positive experience.

Lacoste was one of the first graduate students to work under the supervision of Mikko Taipale, associate professor of molecular genetics. She dedicated nearly eight years to characterizing thousands of rare genetic coding variants involved in disease, which culminated in the first large-scale, publicly available map demonstrating the impact of mutations on where proteins end up in the cell.

After earning her PhD degree, Lacoste joined the Roy and Andrews-Boone labs as a postdoctoral fellow in 2023. While the success of her graduate research afforded her a range of options worth pursuing, she was particularly drawn to a new project on cytochrome P450-bioactivated small molecules for which Roy, Andrews and Boone were seeking a talented researcher to lead. The expertise she had gained in high-throughput biology through her PhD research made Lacoste the ideal candidate for the project.

As a postdoctoral fellow, Lacoste’s current research focuses on combating infections from pathogens and parasites; to this end, Lacoste will conduct a revolutionary drug screen called PEXIL (Paralleled screens for Enzyme-activated Xenobiotic-Induced Lethality). This screen harnesses a family of enzymes, called the cytochrome P450 superfamily, that metabolize drugs and other foreign substances in the body. Humans have 57 of these enzymes, which can convert drugs into bioactive compounds.

Lacoste developed a library of cytochrome P450 enzymes found in infectious organisms and vectors of disease, like mosquitos. She plans to test the enzymes with different drugs to determine if they will bioactivate the drugs to produce compounds that are lethal to the parasite or pathogen, but not to humans. Any drugs that pass the test would then be candidates for treating people with infections. The concept for this project is based on a 2023 study from the Roy lab published in Nature.

“No one has thought of exploiting the cytochrome P450 family in this way,” said Lacoste. “This is why the 2023 Nature study was a major milestone. We see the potential for our drug screen because many P450 enzymes are overexpressed in infectious organisms and vectors of disease, and we can use this against them by targeting those P450s with our library of small molecules.”

Lacoste hopes that her research will identify dozens of drugs that can be further developed into new medicines to treat parasitic and pathogenic infections. Her library of cytochrome P450 strains consists of 272 cytochrome P450 enzymes from six different organisms, including organisms that transmit two of the World Health Organization’s priority global diseases.

After conducting a successful pilot screen last year, Lacoste has recently been working to optimize her library for greater efficiency as well as running additional pilot screens with known small molecules that are bioactivated by a cytochrome P450 enzyme. Her next step is to screen the entire library within a year.

“Jessica is a highly accomplished researcher who possesses passion and drive that have led to her co-author five publications from her PhD work, including in Cell, Nature, Molecular Cell and the Proceedings of the National Academy of Sciences,” said Roy. “This fellowship is well-deserved, and it will allow her to continue important work to help solve the global crisis in infectious disease.”