Sebastien Weyn, a graduating PhD student in the Chaolin Zhang lab, has been awarded the Titus M. Coan Prize for Excellence in Research. Weyn, who intends to participate in the May 13 Hooding Ceremony at the Vagelos College of Physicians and Surgeons (P&S), is one of two graduates who has received the award, bestowed annually by P&S. Weyn is being recognized in the area of outstanding basic cell and molecular research. 

“I am happy to represent Systems Biology for the award, which together with previous DSB winners, showcase the important biological contributions coming from the department,” says Weyn. “Winning this award also speaks greatly to my mentor, Chaolin, and his vision and insight in the field.”

Work in the Zhang lab concentrates on the study of the nervous system and its underlying molecular mechanisms. The group focuses on the function of post-transcriptional gene regulation, in particular a level of molecular regulation called alternative RNA splicing, in the nervous system.

“The regulation of RNA splicing is surprisingly mysterious despite the fact that it is critical for proper cellular function, and there are several genetic diseases that result from improper splicing,” notes Weyn. “Understanding splicing can lead to breakthrough therapies.” 

For his dissertation project, Weyn dissected the regulatory mechanisms underlying dynamic alternative splicing switches during neurodevelopment. His work led to insights into the role that Rbfox proteins have in promoting mature splicing patterns, including in a number of autism candidate risk genes. The Rbfox family of proteins are important regulators of alternative splicing and mutations of these genes have been linked to several neurodevelopmental disorders. 

While a student in the Zhang lab, Weyn also developed a comprehensive reference catalogue of alternative splicing events after investigating how multiple RNA-binding proteins work together to control dynamic splicing switches with precise timing. For the latter, Weyn worked closely with lab members on deep RNA sequencing data of mouse brain at different developmental stages; this work contributed to an expanded list of alternative splicing events, the most exhaustive one to date. 

A paper just accepted by Nature Communications details Weyn’s work, in collaboration with other lab members, that provides mechanistic insights into how the precise timing of dynamic splicing switches is controlled, and how such control differs in different types of nerve cells. This information could potentially lead to further understanding of certain distinct properties of our peripheral nervous system neurons, such as their plasticity and regenerative quality. 

“In addition to his high-quality work in the lab,” says Dr. Zhang , assistant professor of systems biology, “Sebastien is a true team player and gentleman, and one who is always ready to lend a helping hand.” 

Weyn, born and raised in Austin, TX to Belgian parents, completed his undergraduate work in biochemistry at the University of Texas-Austin. In 2012, he joined the Department of Systems Biology when it was not yet an official Columbia department; known then as C2B2, or the Center for Computational Biology and Bioinformatics.

The excitement of joining something on the ground floor and a field set for rapid growth are what attracted Weyn to Columbia’s systems biology integrated program. Though busy with life in the lab, he also found the time to play viola, an instrument he picked up at age 11, and performed regularly with the CUMC Symphony Orchestra and other groups around Columbia.

After his thesis defense in December, Weyn joined Stoke Therapeutics as a bioinformatics scientist. The Bedford, MA-based startup focuses on drug development aimed at treating genetic diseases. 

Indeed, Weyn is on track to realize a key life goal, and it is his persistent interest in science that is taking him there. 

“I’m fascinated by the complexity of biology, because while organisms, as a whole, work quite well and have high fault tolerance, nothing in biology is very clean and it is extremely difficult to come up with a rule that always works,” he says. “However, I am also very aware that the costs of failure can be extremely high, so I want to push forward the discoveries that have been made into actionable results. I hope we will get to a point where we can manage or cure all diseases, and I would like to contribute any small part I can.” 

-Melanie A. Farmer