Matthew G Vander Heiden

Summary

Affiliation: Massachusetts Institute of Technology
Country: USA

Publications

  1. pmc Pyruvate kinase M2 activators promote tetramer formation and suppress tumorigenesis
    Dimitrios Anastasiou
    Department of Medicine, Division of Signal Transduction, Beth Israel Deaconess Medical Center, Boston, MA, USA
    Nat Chem Biol 8:839-47. 2012
  2. pmc Exploiting tumor metabolism: challenges for clinical translation
    Matthew G Vander Heiden
    Koch Institute for Integrative Cancer Research, Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
    J Clin Invest 123:3648-51. 2013
  3. doi Metabolic pathway alterations that support cell proliferation
    M G Vander Heiden
    Massachusetts Institute of Technology, Koch Institute for Cancer Research and Department of Biology, Cambridge, Massachusetts 02139, USA
    Cold Spring Harb Symp Quant Biol 76:325-34. 2011
  4. doi Targeting cancer metabolism: a therapeutic window opens
    Matthew G Vander Heiden
    Koch Institute for Integrative Cancer Research and Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
    Nat Rev Drug Discov 10:671-84. 2011
  5. pmc Reductive glutamine metabolism is a function of the α-ketoglutarate to citrate ratio in cells
    Sarah Maria Fendt
    Department of Chemical Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA
    Nat Commun 4:2236. 2013
  6. pmc IDH1 mutations alter citric acid cycle metabolism and increase dependence on oxidative mitochondrial metabolism
    Alexandra R Grassian
    Authors Affiliations Novartis Institutes for Biomedical Research Koch Institute for Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts Departments of Bioengineering and Pharmacology and Moores Cancer Center, University of California, San Diego, La Jolla, California
    Cancer Res 74:3317-31. 2014
  7. pmc Tracing compartmentalized NADPH metabolism in the cytosol and mitochondria of mammalian cells
    Caroline A Lewis
    The Koch Institute for Integrative Cancer Research at Massachusetts Institute of Technology, Cambridge, MA 02139, USA
    Mol Cell 55:253-63. 2014
  8. pmc Metformin decreases glucose oxidation and increases the dependency of prostate cancer cells on reductive glutamine metabolism
    Sarah Maria Fendt
    Departments of Chemical Engineering and Biology, Massachusetts Institute of Technology, Cambridge, MA02139, USA
    Cancer Res 73:4429-38. 2013
  9. pmc Lack of Evidence for PKM2 Protein Kinase Activity
    Aaron M Hosios
    Koch Institute for Integrative Cancer Research at Massachusetts Institute of Technology, Cambridge, MA 02139, USA
    Mol Cell 59:850-7. 2015
  10. pmc Germline loss of PKM2 promotes metabolic distress and hepatocellular carcinoma
    Talya L Dayton
    David H Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
    Genes Dev 30:1020-33. 2016

Collaborators

Detail Information

Publications28

  1. pmc Pyruvate kinase M2 activators promote tetramer formation and suppress tumorigenesis
    Dimitrios Anastasiou
    Department of Medicine, Division of Signal Transduction, Beth Israel Deaconess Medical Center, Boston, MA, USA
    Nat Chem Biol 8:839-47. 2012
    ..These data support the notion that small-molecule activation of PKM2 can interfere with anabolic metabolism...
  2. pmc Exploiting tumor metabolism: challenges for clinical translation
    Matthew G Vander Heiden
    Koch Institute for Integrative Cancer Research, Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
    J Clin Invest 123:3648-51. 2013
    ..Emerging biomarker strategies to guide drug development are also highlighted. ..
  3. doi Metabolic pathway alterations that support cell proliferation
    M G Vander Heiden
    Massachusetts Institute of Technology, Koch Institute for Cancer Research and Department of Biology, Cambridge, Massachusetts 02139, USA
    Cold Spring Harb Symp Quant Biol 76:325-34. 2011
    ..Together, these findings argue that distinct metabolic phenotypes exist among proliferating cells, and both genetic and environmental factors influence how metabolism is regulated to support cell growth...
  4. doi Targeting cancer metabolism: a therapeutic window opens
    Matthew G Vander Heiden
    Koch Institute for Integrative Cancer Research and Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
    Nat Rev Drug Discov 10:671-84. 2011
    ..Research into how changes in cell metabolism promote tumour growth has accelerated in recent years. This has refocused efforts to target metabolic dependencies of cancer cells as a selective anticancer strategy...
  5. pmc Reductive glutamine metabolism is a function of the α-ketoglutarate to citrate ratio in cells
    Sarah Maria Fendt
    Department of Chemical Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA
    Nat Commun 4:2236. 2013
    ..Thus, targeting reductive glutamine conversion for a therapeutic benefit might require distinct modulations of metabolite concentrations rather than targeting the upstream signalling, which only indirectly affects the process. ..
  6. pmc IDH1 mutations alter citric acid cycle metabolism and increase dependence on oxidative mitochondrial metabolism
    Alexandra R Grassian
    Authors Affiliations Novartis Institutes for Biomedical Research Koch Institute for Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts Departments of Bioengineering and Pharmacology and Moores Cancer Center, University of California, San Diego, La Jolla, California
    Cancer Res 74:3317-31. 2014
    ..Lastly, IDH1-mutant cells also grew poorly as subcutaneous xenografts within a hypoxic in vivo microenvironment. Together, our results suggest therapeutic opportunities to exploit the metabolic vulnerabilities specific to IDH1 mutation...
  7. pmc Tracing compartmentalized NADPH metabolism in the cytosol and mitochondria of mammalian cells
    Caroline A Lewis
    The Koch Institute for Integrative Cancer Research at Massachusetts Institute of Technology, Cambridge, MA 02139, USA
    Mol Cell 55:253-63. 2014
    ..Using this system we determine the direction of serine/glycine interconversion within the mitochondria and cytosol, highlighting the ability of this approach to resolve compartmentalized reactions in intact cells. ..
  8. pmc Metformin decreases glucose oxidation and increases the dependency of prostate cancer cells on reductive glutamine metabolism
    Sarah Maria Fendt
    Departments of Chemical Engineering and Biology, Massachusetts Institute of Technology, Cambridge, MA02139, USA
    Cancer Res 73:4429-38. 2013
    ..These data suggest that interfering with glutamine may synergize with metformin to improve outcomes in patients with prostate cancer...
  9. pmc Lack of Evidence for PKM2 Protein Kinase Activity
    Aaron M Hosios
    Koch Institute for Integrative Cancer Research at Massachusetts Institute of Technology, Cambridge, MA 02139, USA
    Mol Cell 59:850-7. 2015
    ..In addition, we also failed to observe PKM2-dependent transfer of phosphate from ATP directly to protein. These findings argue against a role for PKM2 as a protein kinase...
  10. pmc Germline loss of PKM2 promotes metabolic distress and hepatocellular carcinoma
    Talya L Dayton
    David H Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
    Genes Dev 30:1020-33. 2016
    ..Therefore, in addition to its role in cancer metabolism, PKM2 plays a role in controlling systemic metabolic homeostasis and inflammation, thereby preventing HCC by a non-cell-autonomous mechanism...
  11. pmc Pyruvate kinase isoform expression alters nucleotide synthesis to impact cell proliferation
    Sophia Y Lunt
    Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA Department of Physiology, Michigan State University, East Lansing, MI 48824, USA
    Mol Cell 57:95-107. 2015
    ..Thus, PKM1 expression promotes a metabolic state that is unable to support DNA synthesis. ..
  12. pmc An epitope tag alters phosphoglycerate dehydrogenase structure and impairs ability to support cell proliferation
    Katherine R Mattaini
    Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139 USA Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139 USA
    Cancer Metab 3:5. 2015
    ..These studies will require a physiologically relevant form of the enzyme for experiments using engineered cell lines and recombinant protein...
  13. pmc Environment Impacts the Metabolic Dependencies of Ras-Driven Non-Small Cell Lung Cancer
    Shawn M Davidson
    Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02142, USA Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA Broad Institute of MIT and Harvard University, Cambridge, MA 02142, USA
    Cell Metab 23:517-28. 2016
    ..Furthermore, these data argue that the in vivo environment is an important determinant of the metabolic phenotype of cancer cells. ..
  14. pmc PKM2 isoform-specific deletion reveals a differential requirement for pyruvate kinase in tumor cells
    William J Israelsen
    Koch Institute for Integrative Cancer Research at Massachusetts Institute of Technology, Cambridge, MA 02139, USA
    Cell 155:397-409. 2013
    ..These data suggest that regulation of PKM2 activity supports the different metabolic requirements of proliferating and nonproliferating tumor cells...
  15. doi Allosteric regulation of PKM2 allows cellular adaptation to different physiological states
    Dan Y Gui
    Koch Institute for Integrative Cancer Research at Massachusetts Institute of Technology, Cambridge, MA 02139, USA
    Sci Signal 6:pe7. 2013
    ..These findings add additional complexity to how PKM2 is regulated in cells and support the notion that modulating PKM2 activity enables cells to adapt their metabolic state to specific physiological contexts...
  16. doi Aerobic glycolysis: meeting the metabolic requirements of cell proliferation
    Sophia Y Lunt
    Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
    Annu Rev Cell Dev Biol 27:441-64. 2011
    ....
  17. pmc Amino Acids Rather than Glucose Account for the Majority of Cell Mass in Proliferating Mammalian Cells
    Aaron M Hosios
    Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
    Dev Cell 36:540-9. 2016
    ....
  18. pmc Biophysical changes reduce energetic demand in growth factor-deprived lymphocytes
    Vivian C Hecht
    Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139 Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139
    J Cell Biol 212:439-47. 2016
    ..The response reduces cell surface area to minimize energy expenditure while conserving biomass, suggesting that the biophysical properties of cells can be regulated to promote survival under conditions of nutrient stress. ..
  19. pmc Supporting Aspartate Biosynthesis Is an Essential Function of Respiration in Proliferating Cells
    Lucas B Sullivan
    The Koch Institute for Integrative Cancer Research and Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
    Cell 162:552-63. 2015
    ..Together, these data argue a major function of respiration in proliferating cells is to support aspartate synthesis...
  20. pmc Cell-state-specific metabolic dependency in hematopoiesis and leukemogenesis
    Ying Hua Wang
    Center for Regenerative Medicine and Cancer Center, Massachusetts General Hospital, Boston, MA 02114, USA Harvard Stem Cell Institute, Cambridge, MA 02114, USA Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA
    Cell 158:1309-23. 2014
    ..This finding suggests that fine-tuning the level of glycolysis may be explored therapeutically for treating leukemia while preserving HSC function. ..
  21. pmc Elevation of circulating branched-chain amino acids is an early event in human pancreatic adenocarcinoma development
    Jared R Mayers
    1 Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA 2 Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA
    Nat Med 20:1193-8. 2014
    ..Together, these findings suggest that increased whole-body protein breakdown is an early event in development of PDAC. ..
  22. pmc Antibody-mediated neutralization of perfringolysin o for intracellular protein delivery
    Nicole J Yang
    Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States
    Mol Pharm 12:1992-2000. 2015
    ....
  23. pmc Pyruvate kinase: Function, regulation and role in cancer
    William J Israelsen
    Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA Electronic address
    Semin Cell Dev Biol 43:43-51. 2015
    ..Here we review the structure, function, and regulation of pyruvate kinase and discuss how these properties enable regulation of PKM2 for cell proliferation and tumor growth. ..
  24. pmc EGLN1 Inhibition and Rerouting of α-Ketoglutarate Suffice for Remote Ischemic Protection
    Benjamin A Olenchock
    Division of Cardiovascular Medicine, Department of Medicine, The Brigham and Women s Hospital, Boston, MA 02115, USA Harvard Medical School, Boston, MA 02115, USA Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
    Cell 164:884-95. 2016
    ..Egln1 loss causes accumulation of circulating αKG, which drives hepatic production and secretion of kynurenic acid (KYNA) that is necessary and sufficient to mediate cardiac ischemic protection in this setting. ..
  25. pmc Famine versus feast: understanding the metabolism of tumors in vivo
    Jared R Mayers
    Koch Institute for Integrative Cancer Research and Department of Biology, Massachusetts Institute of Technology MIT, Cambridge, MA, USA
    Trends Biochem Sci 40:130-40. 2015
    ..Whole-body metabolism and tumor heterogeneity also influence the metabolism of tumor cells, and successful targeting of metabolism for cancer therapy will require an understanding of tumor metabolism in vivo. ..
  26. pmc Small molecule activation of PKM2 in cancer cells induces serine auxotrophy
    Charles Kung
    Agios Pharmaceuticals, 38 Sidney Street, Cambridge, MA 02139, USA
    Chem Biol 19:1187-98. 2012
    ..These data support the hypothesis that PKM2 expression confers metabolic flexibility to cancer cells that allows adaptation to nutrient stress...
  27. pmc Pyruvate as a pivot point for oncogene-induced senescence
    Benjamin A Olenchock
    Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
    Cell 153:1429-30. 2013
    ..A new report in the journal Nature by Kaplon et al. suggests that driving pyruvate oxidation can thwart tumor growth in BRAF-driven melanoma by inducing oncogene-induced senescence, a finding that might be exploited therapeutically. ..
  28. pmc Reductive glutamine metabolism by IDH1 mediates lipogenesis under hypoxia
    Christian M Metallo
    Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
    Nature 481:380-4. 2012
    ..These results identify a critical role for oxygen in regulating carbon use to produce AcCoA and support lipid synthesis in mammalian cells...