Other Web Profiles:
Biochemical and Molecular Nutrition
Immunometabolism; Cancer metabolism; dynamic metabolic regulation
Mammalian cellular metabolism is a dynamic process that consists of thousands of interconnected reactions and regulatory interactions. While the architecture of metabolic networks is defined by the genome, actual metabolic activity (i.e. metabolic flux) through the pathways varies greatly. Dynamic reprogramming of metabolism enables cells to meet metabolic needs associated with specific cellular states and cellular functions (such as supporting proliferation or activating immune function), and adapt to changes in the environment. The overarching goal of my research is to understand how mammalian cellular metabolism is reprogrammed in response to changes in the environment and cellular state, and how key metabolic activities in turn affect cell physiology. To study this, I combine systematic approaches, especially metabolomics, lipidomics and fluxomics, with targeted biochemical and genetic techniques. Currently, my lab focuses on two main areas: (1) understanding how metabolic reprogramming affects the inflammatory state in macrophages and neutrophils, and (2) understanding how specific conditions in the tumor microenvironment impact the metabolism and behavior of immune cells and cancer cells.
Seim GL, Britt EC, John SV, Yeo FJ, Johnson AR, Eisenstein RS, Pagliarini DJ, Fan J. (2019) Two-stage metabolic remodelling in macrophages in response to LPS and interferon-γ stimulation. Nature Metabolism 1, 731–742
Fan J*, Teng X*, Liu L, Mattaini KR, Looper RE, Vander Heiden MG, Rabinowitz JD. Human Phosphoglycerate Dehydrogenase Produces the Oncometabolite d-2-Hydroxyglutarate. (2015) ACS Chem. Biol. 10(2):510-6.
Fan J, Krautkramer KA, Feldman JL, Denu JM. (2015) Metabolic regulation of histone post-translational modifications. ACS Chem. Biol. 10(1):95-108
Zhang J, Fan J, Venneti S, Cross JR, Takagi T, Bhinder B, Djaballah H, Kanai M, Cheng EH, Judkins AR, Pawel B, Baggs J, Cherry S, Rabinowitz JD, Thompson CB. (2014) Asparagine plays a critical role in regulating cellular adaptation to glutamine depletion. Mol. Cell. 56(2):205-18
Fan J*, Ye J*, Kamphorst JJ, Shlomi T, Thompson CB, Rabinowitz JD. (2014) Quantitative flux analysis reveals folate-dependent NADPH production. Nature. 510(7504):298-302.
Fan J, Kamphorst JJ, Mathew R, Cheung MK., White E, Shlomi T, Rabinowitz JD. (2013) Simultaneous aerobic glycolysis and glutamine-supported oxidative ATP production in oncogene-driven renal epithelial cells. Mol. Syst. Biol. 9: 712.
Kamphorst JJ*, Cross JR*, Fan J, De Stanchina E, Mathew R, White E, Thompson CB, Rabinowitz JD. (2013) Hypoxia and oncogenic Ras trigger scavenging of fatty acids from lysophospholipids. Proc. Nat. Acad. Sci. 110(22):8882-7
Guo JX*, Chen HY*, Mathew R*, Fan J*, Strohecker AM, Karsli-Uzunbas G, Kamphorst JJ,Chen G, Lemmons JM, Karantza V, Coller HA, DiPaola RS, Gelinase C, Rabinowitz, JD, White E. (2011) Activated Ras Requires Autophagy to Maintain Oxidative Metabolism and Tumorigenesis. Genes Dev. 25(5):460-70