# Christian Dibble Assistant Professor of Pathology ![dibble_christian_1.jpg](/sites/g/files/omnuum3501/files/styles/hwp_4_5__480x600/public/dms/files/dibble_christian_1.jpg?itok=L9MPHOsj) location\_on Beth Israel Deaconess Medical Center Center for Life Sciences, 4th Floor, Room 413 3 Blackfan Circle Boston, MA 02115 smartphone [617-735-2889](tel:617-735-2889) email laptop\_windows [Lab Website](https://www.dibblelab.com/) laptop\_windows [Publications](https://www.ncbi.nlm.nih.gov/myncbi/163tCNKcs1RAD/bibliography/public/) The Dibble Lab is focused on understanding the regulatory relationship between cellular signaling and metabolic pathways. In particular, we are interested in discovering new mechanisms through which insulin and growth factor stimulated signaling pathways, such as the PI3K-mTOR pathway, control metabolic activity. We are also interested in characterizing any mechanism through which biosynthesis of the pivotal cofactor Coenzyme A (CoA) is regulated to coordinate CoA supplies with the demands of lipid metabolism and other CoA-dependent metabolic processes. Physiological activation of PI3K by insulin in response to feeding, stimulates uptake of nutrients (especially glucose) and anabolic metabolism, thus tying cellular metabolism to the systemic metabolic status of the organism. In cancer, PI3K signaling becomes growth factor-independent due to mutations in PI3K itself (PIK3CA is the second most-commonly mutated gene in cancer) or in major upstream cancer drivers (e.g. EGFR, MET, KRAS, PTEN). Although a great deal is known about how insulin and PI3K control cellular metabolism, we believe that many additional regulatory mechanisms remain to be uncovered. For instance, my lab (in collaboration with the Toker lab) recently discovered that PI3K signaling stimulates the biosynthesis of CoA from Vitamin B5 and identified the metabolite phosphatase, PANK4, as a novel suppressor of CoA synthesis and target of PI3K signaling. Ultimately, this regulatory axis controls downstream CoA-dependent processes including mitochondrial respiration, lipid synthesis, histone acetylation, and growth. Building on this discovery, we are using mass spectrometry-based metabolomics and lipidomics, biochemistry, mammalian cell culture, and mouse knockout models to further understand how signaling pathways and metabolites control CoA metabolism and how essential nutrients required for CoA metabolism are sensed by the cell. In addition, through collaborations, we are taking advantage of other model systems such as *Drosophila* to study these signaling and metabolic pathways in vivo. Ultimately, the hope is to deepen our understanding of the PI3K-mTOR-dependent metabolic program in both normal tissues such as the kidney and liver, and in tumors. Dependencies within this signaling-metabolism nexus may be therapeutically exploited in a way that provides a greater therapeutic window compared to the targeting of signaling pathways directly. - ## Faculty [BBS](/faculty/bbs)