David Barbie

David Barbie

Assistant Professor of Medicine
David Barbie
Our laboratory is broadly interested in targeting cancer innate immunity and in building novel technologies to model cancer immunotherapy response. We have developed a microfluidic ex vivo system for culture of primary organotypic tumor spheroids that is capable of modeling response to PD-1 blockade and other cancer immunotherapies, and have utilized this platform to demonstrate the potential of TBK1 and CDK4 inhibition to enhance anti-PD-1 response. In addition, we are building more physiologic ex vivo models of the tumor microenvironment that incorporate tumor vasculature, and are developing high resolution readouts of dynamic immunotherapy response in this system using single cell RNA sequencing. Most recently we have turned our attention to co-opting TBK1 signaling and its specific engagement of IRF3 to drive viral sensing in tumors as a way to promote immunogenicity. Furthermore, these studies have identified KRAS-LKB1 (KL) mutant non-small cell lung cancer, as well as small cell lung cancer (SCLC), as two key subtypes that epigenetically silence STING and thus avoid effective T cell infiltration and antigen presentation as a means of escaping anti-tumor immunity.  The major current focus of our laboratory thus involves combining epigenetic inhibitors of enzymes that de-repress these viral sensing pathways (e.g. EZH2) with STING agonists. Indeed we have recently demonstrated that this combination therapy reverses immune suppression and results in robust tumor rejection in a SCLC syngeneic mouse tumor model. Additionally, we have been collaborating with the Reinherz laboratory using their ultrasensitive mass spectrometry technique to begin to define specific endogenous retroviral tumor antigens that could mediate this rejection and play a more general role as T cell targets for effective anti-cancer immunity in humans.  

Contact Information

Dana Farber Cancer Institute
44 Binney Street
Boston, MA 02115
p: 617-726-2862