Mechanism of cGAS-STING Inactivation in Antitumor Immunity and Disease

2020 Emerging Leader Award

Philip Kranzusch, PhD, Dana-Farber Cancer Institute

Dr. Kranzusch is investigating how the signaling molecule cGAMP is controlled within cells, research that is critical for the rational design of next-generation anti-cancer immunotherapies. cGAMP carries immunity-stimulating signals between the enzyme cGAS and the receptor STING, which can spread rapidly from cell to cell to activate a widespread antitumor immune response. Researchers in the Kranzusch laboratory are studying the mechanism and downstream immune effects of cGAMP regulation, including identifying the key biological factors involved in cGAMP degradation. Dr. Kranzusch earned his PhD from Harvard University and completed postdoctoral studies at University of California, Berkeley. In 2016 he started as an Assistant Professor of Microbiology at Harvard Medical School and the Dana-Farber Cancer Institute. The Kranzusch Lab uses a biochemical and structural biology approach to understand the immune response to cancer.

published research

Eaglesham JB, McCarty KL, Kranzusch PJ. Structures of diverse poxin cGAMP nucleases reveal a widespread role for cGAS-STING evasion in host-pathogen conflict. Elife. 2020.

Govande AA, Duncan-Lowey B, Eaglesham JB, Whiteley AT, Kranzusch PJ. Molecular basis of CD-NTase nucleotide selection in CBASS anti-phage defense. Cell Rep. 2021.

Slavik KM, Morehouse BR, Ragucci AE, Zhou W, Ai X, Chen Y, Li L, Wei Z, Bähre H, König M, Seifert R, Lee ASY, Cai H, Imler JL, Kranzusch PJ. cGAS-like receptors sense RNA and control 3’2′-cGAMP signaling in Drosophila. Nature. 2021.