The Schug Laboratory
Alterations in the acquisition and metabolism of nutrients are now firmly recognized as hallmarks of cancer development. It is now known that tumor cell metabolism is influenced not only by its metabolic state, but also by the nutrients that are available to it. For instance, when cancer cells invade other tissues during metastasis, the nutrients that are available in the new tissue can be drastically different from where the tumor cell originated. Furthermore, within a single tumor mass some regions can experience nutrient and oxygen deficiencies (also known as hypoxia) due to poorly formed blood vessels. During these various conditions of nutrient stress, cancer cells are forced to adapt their metabolism to use the available resources in order to grow and survive.
The Schug laboratory seeks to characterize the metabolic adaptations that occur in metastatic tumors and in tumors that are under hypoxia and nutrient stress with the intent of exploiting these changes as novel therapeutic modalities. They use pre-clinical models and state-of-the-art metabolomic, proteomic, and transcriptomic approaches to uncover novel metabolic vulnerabilities in cancer. These new targets are then fed into an active drug discovery program to develop effective compounds for the improved treatment of cancer patients.
Katelyn Miller, Ph.D.
Veglia, F., Tyurin, V.A., Blasi, M., De Leo, A., Kossenkov, A.V., Donthireddy, L., Schug, Z., Basu, S., Wang, F., Ricciotti, E., DiRusso, C., Murphy, M.E., Vonderheide, R.H., Lieberman, P.M., Mulligan, C., Nam, B., Hockstein, N., Masters, G., Guarino, M., Lin, C., Nefedova, Y., Black, P., Kagan, V.E., Gabrilovich, D.I. “Fatty acid transport protein 2 reprograms neutrophils in cancer.” Nature. 2019 May;569(7754):73-78. doi: 10.1038/s41586-019-1118-2. Epub 2019 Apr 17.
Patel, S., Fu, S., Mastio, J., Dominguez, G.A., Purohit, A., Kossenkov, A., Lin, C., Alicea-Torres, K., Sehgal, M., Nefedova, Y., Zhou, J., Languino, L.R., Clendenin, C., Vonderheide, R.H., Mulligan, C., Nam, B., Hockstein, N., Masters, G., Guarino, M., Schug, Z.T., Altieri, D.C., Gabrilovich, D.I. " Unique pattern of neutrophil migration and function during tumor progression." Nat Immunol. 2018 Nov;19(11):1236-1247. doi: 10.1038/s41590-018-0229-5. Epub 2018 Oct 15.
Schug, Z.T., Vande Voorde, J., Gottlieb, E. "The metabolic fate of acetate in cancer." Nat Rev Cancer. 2016 Nov;16(11):708-717. doi: 10.1038/nrc.2016.87. Epub 2016 Aug 26.
Peck, B., Schug, Z.T., Schulze, A., et al. "Inhibition of fatty acid desaturation is detrimental to cancer cell survival in metabolically compromised environments." Cancer Metab. 2016 Apr 1;4:6. doi: 10.1186/s40170-016-0146-8. eCollection 2016.
Schug, Z.T., Peck, B., Gottlieb, E., et al. "Acetyl-CoA synthetase 2 promotes acetate utilization and maintains cancer cell growth under metabolic stress." Cancer Cell. 2015 Jan 12;27(1):57-71. doi: 10.1016/j.ccell.2014.12.002.