He is best known for his discovery of mechanisms by which nucleic acids trigger innate and autoimmune responses from the interior of a cell, work for which he received the 2019 Breakthrough Prize in Life Sciences.
He then spent three years working as a senior scientist at biotech firm ProScript in Cambridge, Massachusetts, where he developed assays that helped to identify and improve the cancer treatment Velcade.
[3][5] Working with Tom Maniatis of Harvard University in 1996, Chen found that the enzyme kinase had to be "activated" by ubiquitin in order for the NF-κB signalling process to function properly.
He decided pursuing his research into ubiquitin would be more suited for work in academia and left ProScript in 1997 to start a lab at the University of Texas Southwestern Medical Center in Dallas.
[4] His research received grant funding from the Burroughs Wellcome Fund in 2002[6] enabling research into how NF-κB initiated immune responses to RNA viruses such as influenza and hepatitis C. This new line of research led to the discovery of MAVS (Mitochondrial Anti-Viral Signaling protein) and the role of mitochondria in antiviral innate immune responses, and the more recent discoveries of the cytosolic DNA sensor, Cyclic GMP-AMP synthase (cGAS; cGAMP synthase), and a new second messenger, Cyclic guanosine monophosphate–adenosine monophosphate (cyclic GMP-AMP, cGAMP), which play key roles in immune defense as well as autoimmune diseases.