David Knowles Wins NSF CAREER Award

Award supports computer scientist’s work to develop bioinformatics tools and methods to better understand RNA splicing’s role in ALS, cancer, and neuron development.

Feb 23 2022 | By Bernadette Young
David Knowles headshot

David Knowles, assistant professor of computer science, has won a National Science Foundation CAREER Award to develop a new conceptual framework that will fundamentally transform how alternative splicing (AS) is analyzed. AS is the crucial cellular process by which "junk" regions are removed from initially transcribed RNA. Splicing is tightly regulated in healthy organismal development but frequently dysregulated in diseases such as ALS and cancer.

Knowles will use his expertise in statistical machine learning and its application in genomics to create the new framework and tools. The five-year, $500,000 award will enable Knowles to expand the power of LeafCutter, a method he co-developed to quantify RNA splicing from short-read RNA-seq data and test for differences between conditions. With this new project, he plans to design more accurate and powerful algorithms to analyze both single-cell and long-read RNA-seq. These tools will help researchers understand the role of AS in organismal development, disease, and environmental response at unprecedented resolution.

“RNA splicing is known to be a crucial cellular process but its importance in genetic disease, cellular response, and organismal development is often overlooked,” said Knowles, who joined Columbia Engineering in 2019. He is also a member of the Data Science Institute, an interdisciplinary appointee in Systems Biology, and a Core Faculty Member at the New York Genome Center (NYGC). “This proposal will fund our development of tools to more easily and effectively interrogate splicing’s role in diverse biological systems with potential applications in biomedicine, agriculture, and basic biology.”

One of the most prestigious honors given to promising junior faculty, the NSF CAREER award will support Knowles’ long-term career goal to design bioinformatics tools needed to detect and interpret AS. He will work with colleagues at NYGC to develop these tools that will have real-world applications to better understand splicing’s role in gene regulation, the development of neurons, and disease.