Researcher Highlight: Ryan Hili
Researcher Highlight: Ryan Hili
Dr. Ryan Hili is an Associate Professor in the Department of Chemistry at York University, where his research focuses on nucleic acid chemical biology. His group is particularly interested in how the intrinsic properties of nucleic acids can be harnessed to create functional molecules and to probe biological systems. Ryan completed his Ph.D. in Chemistry at the University of Toronto in the laboratory of Prof. Andrei K. Yudin, where he worked on the development of highly strained molecules as tools for organic synthesis. He then carried out postdoctoral research at Harvard University in the laboratory of Prof. David R. Liu, where he developed an interest in nucleic acid chemical biology. This transition—from synthetic methodology to biomolecular function—continues to shape the perspective of his research programme.
In his independent career, Ryan initially focused on expanding the chemical and functional capabilities of nucleic acids. His group developed approaches for the combinatorial synthesis of nucleic acid polymers that enable the construction of sequence-defined libraries with substantial chemical diversity. These systems were used to evolve highly modified single-stranded nucleic acids as antibody mimetics. In parallel, his lab developed novel ways of generating and screening DNA-encoded libraries (DELs) for applications in drug discovery.
Inspired by the rich chemical diversity of RNA, his research has shifted toward RNA epitranscriptomics. His group develops chemistry-driven sequencing technologies to map post-transcriptional RNA modifications with high precision. These include “nitrite sequencing” for detecting m6A and “PhOxi-seq” for detecting m2G in RNA at single-nucleotide resolution. “We tend to approach RNA as organic chemists,” says Ryan. “Rather than relying on affinity or enrichment strategies, we ask whether there are intrinsic chemical differences between modified and unmodified nucleobases that we can exploit. If we can selectively transform a modified base while leaving the canonical bases untouched, we can effectively ‘write’ that information into the sequence itself.” These tools are now being applied to understand how specific RNA modifications regulate gene expression and contribute to human disease, while also using his DEL platforms to discover small molecules to interrogate these biological pathways.
Ryan is excited to see the growing interest of organic chemists in nucleic acids research. “What I find exciting about RNA biology right now is that many of the key biological questions hinge on chemical details,” he notes. “Canada has a large and growing nucleic acids chemistry community, which are pushing the envelope in this research space.”
Outside of his research, Ryan plays multiple instruments and composes music spanning several genres. He is also engaged in the Canadian RNA community through conference organization and outreach activities through RNA Canada ARN and Canadian Society of Chemistry.
Click here to visit the Hili lab website. Thank you Ryan!
