Professor Benoit Chabot

Written by: Dr. Julieta Rivosecchi
Edited by: Dr. Paula Petronela Groza

Have you ever dreamed of training with a pioneer in RNA research, establishing your own lab, collaborating with scientists around the world, mentoring young investigators, pushing the boundaries of your field, launching your own biotech company, and being a distinguished leader in the RNA Society? Draw inspiration from the academic journey of Benoit Chabot, Professor in the Department of Microbiology, Faculty of Medicine and Health Sciences, at the Université de Sherbrooke, Canada.

            Since his PhD with Professor Joan Steitz at Yale University in New Haven, USA, Prof. Chabot has been captivated by the alternative splicing field. “After a fantastic PhD experience on the role of snRNPs in splicing, I deviated to do a relatively short but productive post-doc in mouse genetics in Toronto, Canada. During that time many examples of alternative splicing in mammalian cells were emerging with a clear demonstration of their functional importance. These discoveries triggered my interest in understanding how splicing decisions were controlled, and I came back to the fold!” Hence, his lab investigates basic principles of splicing regulation but also disease-associated splicing mis-regulation, aiming to develop RNA therapies based on splicing reprogramming.

Prof. Chabot recognizes that his first discovery at Steitz lab, demonstrating U2 snRNP's interaction with the intron branch site, represents a defining moment in his career, but it was not the only one. He experienced similar moments of excitement throughout his journey: “Uncovering that serine/arginine-rich (SR) proteins were binding to splicing enhancers (Genes Dev 1993), when we showed that hnRNP A1 could modulate splicing (PNAS 1994 and PLoS Biol 2006) or telomere length in vivo (Nature Genet 1998) or when we uncovered that our genome harbours rapidly evolving repetitive elements that serve as breeding grounds for the production of new splice variants (PNAS 2007).” He acknowledges that many questions leading to these discoveries came from students in the lab. He explains: “A student urged me to investigate a gene that produced functionally important splice variants. This led us to Bcl-x, a gene that determines cell life or death. Similarly, another student's enthusiasm recently propelled our work on the link between splicing and cellular senescence.” Therefore, he encourages graduate students to pursue a problem that genuinely piques their interest. "When attending seminars, challenge yourself to formulate questions – voice them or jot them down. This practice refines how you listen and translates into a more effective approach to your own research, and life in general.”

From his graduate studies to one of the most challenging hurdles in his scientific career –establishing a new lab– Prof. Chabot benefited from encouraging mentors and a supportive research environment. Professors Joe Gall, Peter Moore, and Alan Weiner at Yale were particularly inspiring, as were Joan Steitz and Alan Bernstein who taught him attention to detail and unconventional thinking, respectively. He also found inspiration in Stephen Jay Gould’s works: “Gould emphasized the wonder and discovery inherent in the scientific process, he challenged traditional thinking and encouraged a critical approach to established ideas.” Nowadays, Prof. Chabot continues to draw inspiration from discussions with colleagues in hallways and brainstorming sessions.

“Pursue a problem that genuinely piques your interest. When attending seminars, challenge yourself to formulate questions – voice them or jot them down. This practice refines how you listen and translates into a more effective approach to your own research, and life in general.”

During his career, Prof. Chabot also experienced the challenge of transitioning from basic to translational research. Based on the observation that hnRNP A1 could modulate telomere length, he co-founded the biotech company Telogene Inc. (2000-2005) to exploit its potential applications in cancer. This entrepreneurship experience fuelled his desire to pursue research with therapeutic potential. However, he highlights that these endeavours are challenging due to hardship in securing funding. Obtaining financial support for visionary ideas is a hard task also in academia. Even after 35 years in the field of alternative splicing, Prof. Chabot faces challenges: “It is a complex and relatively understudied field. Convincing colleagues to consider this additional layer of complexity in their projects can be challenging. Securing funding is another hurdle, particularly in Canada. While basic research is crucial for advancements, researchers are pressured to innovate and prioritize translational research. Innovation inherently carries risk. However, funding agencies and companies often seek to minimize risk in translational endeavours, creating a frustrating disconnect.”  Nevertheless, he remains optimistic: “The future of RNA research is undoubtedly bright, particularly in RNA-based therapeutic applications. As more successful examples of targeted RNA delivery emerge, the involvement of health-related companies is certain to grow.”

Prof. Chabot has been a member of the RNA Society since its founding and has played an essential part, serving as a lead organizer or a co-organizer of the Annual Meetings, and chair of the Meetings Committee. He is convinced that: “These gatherings are so much more than just presentations of the latest research. They offer students a golden opportunity to network with leading scientists in the field, gain valuable insights, and chart their future career paths. The interactions that occur at these meetings can spark new collaborations and ultimately accelerate scientific breakthroughs.”  One of his most cherished memories from an RNA Society meeting involves his students. He recalls: “I had four of my graduate students presenting their first posters on the same night at the Banff Meeting in 2001. It gave me a lot of pleasure to see how super-excited they were to greet the constant flow of people interested in their work.”  In 2023, Prof. Chabot received the RNA Society Lifetime Achievement in Service Award for his long-standing contribution to the community. When asked how his commitment to the Society impacted his career, he said: “This leadership role provided invaluable opportunities to collaborate with dedicated colleagues, which has undoubtedly been one of the most rewarding aspects of my career.”

Several research articles from Prof. Chabot’s lab were published in the RNA journal, positively affecting his career: “These publications, cited over 385 times to date, significantly enhanced the visibility and reputation of my lab, which ultimately benefited our funding efforts. I am confident that the journal's strong reputation also made my students more competitive for awards and fellowships.”  Prof. Chabot enjoyed the 2015 issue celebrating 20 years of the RNA journal because of the stimulating mixture of personal history and insights. His favorite article from the RNA journal is the one on naturally or artificially deficient spliceosomes by his Canadian colleagues Naomi Fast, Andrew MacMillan, and Stephen Rader.

Even after a lifetime of RNA research, Prof. Chabot still finds RNA a fascinating world which “allows one to connect with many fields.”  His own findings are a testimony for this “from basic principles of splicing regulation to cell death, cancer and other diseases, aging, evolution, and then uncovering ways to reprogram splicing decisions for the benefit of human health. His passion for RNA goes beyond a single molecule and he is able to find “RNA” everywhere he looks, including “alteRNAtive.”  As he puts it: “I think that it reflects so perfectly what RNA and RNA binding proteins do, and the surprises that inevitably come when one studies them.”

You can find further inspiration from Prof. Chabot’s academic journey on his LinkedIn page: https://www.linkedin.com/in/benoit-chabot-5599451a/