Deciphering Organellar Oxidative Metabolism in Kras-Driven Cancers


2021 Emerging Leader Award

Kıvanç Birsoy, PhD, Rockefeller University

Kıvanç Birsoy, PhD

Dr. Birsoy is using novel genetic tools to decipher the ways that tumor cells can overcome the toxic effects of reactive oxygen species (ROS) in different subcellular organelles. A better understanding of how the balance of reduction–oxidation is maintained in different cellular compartments could contribute to the development of cancer therapies that target ROS detoxification pathways. Dr. Birsoy aims to understand the role of oxidative metabolism in the initiation and progression of Ras-driven lung tumors, as well as to determine how mitochondrial glutathione modulates the immune response during tumor formation and in response to immunotherapy.

Dr. Birsoy received his undergraduate degree from Bilkent University in Turkey and a PhD from Rockefeller University. He completed a postdoctoral fellowship at the Whitehead Institute of the Massachusetts Institute of Technology. Dr. Birsoy’s lab studies how metabolic pathways regulate biological processes and contribute to various diseases including cancer.

PUBLISHED RESEARCH

Wang Y, Yen FS, Zhu XG, Timson RC, Weber R, Xing C, Liu Y, Allwein B, Luo H, Yeh HW, Heissel S, Unlu G, Gamazon ER, Kharas MG, Hite R, Birsoy K. SLC25A39 is necessary for mitochondrial glutathione import in mammalian cells. Nature. 2021.

Unlu G, Prizer B, Erdal R, Yeh HW, Bayraktar E, Birsoy K. Metabolic-scale gene activation screens identify SLCO2B1 as a heme transporter that enhances cellular iron availability. Mol Cell. 2022.

Garcia-Bermudez J, Badgley MA, Prasad S, Baudrier L, Liu Y, La K, Soula M, Williams RT, Yamaguchi N, Hwang RF, Taylor LJ, de Stanchina E, Rostandy B, Alwaseem H, Molina H, Bar-Sagi D, Birsoy K. Adaptive stimulation of macropinocytosis overcomes aspartate limitation in cancer cells under hypoxia. Nat Metab. 2022.

Liu Y, Birsoy K. Metabolic sensing and control in mitochondria. Mol Cell. 2023.

Kenny TC, Khan A, Son Y, Yue L, Heissel S, Sharma A, Pasolli HA, Liu Y, Gamazon ER, Alwaseem H, Hite RK, Birsoy K. Integrative genetic analysis identifies FLVCR1 as a plasma-membrane choline transporter in mammals. Cell Metab. 2023.

Timson RC, Khan A, Uygur B, Saad M, Yeh HW, DelGaudio NL, Weber R, Alwaseem H, Gao J, Yang C, Birsoy K. Development of a mouse model expressing a bifunctional glutathione synthesizing enzyme to study glutathione limitation in vivo. J Biol Chem. 2024.

Son Y, Kenny TC, Khan A, Birsoy K, Hite RK. Structural basis of lipid head group entry to the Kennedy pathway by FLVCR1. Nature. 2024.

Khan A, Unlu G, Lin P, Liu Y, Kilic E, Kenny TC, Birsoy K, Gamazon ER. Metabolic gene function discovery platform GeneMAP identifies SLC25A48 as necessary for mitochondrial choline import. Nat Genet. 2024.

Soula M, Unlu G, Welch R, Chudnovskiy A, Uygur B, Shah V, Alwaseem H, Bunk P, Subramanyam V, Yeh HW, Khan A, Heissel S, Goodarzi H, Victora GD, Beyaz S, Birsoy K. Glycosphingolipid synthesis mediates immune evasion in KRAS-driven cancer. Nature. 2024.

BACK TO OUR PORTFOLIO