Brendan D Manning


Affiliation: Harvard University
Country: USA


  1. Hoxhaj G, Ben Sahra I, Lockwood S, Timson R, Byles V, Henning G, et al. Direct stimulation of NADP+ synthesis through Akt-mediated phosphorylation of NAD kinase. Science. 2019;363:1088-1092 pubmed publisher
    ..These data indicate that Akt-mediated phosphorylation of NADK stimulates its activity to increase NADP+ production through relief of an autoinhibitory function inherent to its amino terminus. ..
  2. Manning B. Adaptation to starvation: translating a matter of life or death. Cancer Cell. 2013;23:713-5 pubmed publisher
    ..In a recent issue of Cell, Leprivier and colleagues demonstrate that eEF2K, which can inhibit translation elongation acutely during protein synthesis, is a critical switch in the survival versus death fate of starved cancer cells. ..
  3. Ricoult S, Dibble C, Asara J, Manning B. Sterol Regulatory Element Binding Protein Regulates the Expression and Metabolic Functions of Wild-Type and Oncogenic IDH1. Mol Cell Biol. 2016;36:2384-95 pubmed publisher
    ..Treatment of cells with 25-hydroxycholesterol or statins, which respectively inhibit or activate SREBP, further supports SREBP-mediated regulation of IDH1 and, in cells with oncogenic IDH1, carbon flux into 2-HG. ..
  4. Huang J, Manning B. A complex interplay between Akt, TSC2 and the two mTOR complexes. Biochem Soc Trans. 2009;37:217-22 pubmed publisher
    ..The present review discusses our current understanding of the increasingly complex functional interactions between Akt, the TSC1-TSC2 complex and mTOR, which are fundamentally important players in a large variety of human diseases. ..
  5. Howell J, Hellberg K, Turner M, Talbott G, Kolar M, Ross D, et al. Metformin Inhibits Hepatic mTORC1 Signaling via Dose-Dependent Mechanisms Involving AMPK and the TSC Complex. Cell Metab. 2017;25:463-471 pubmed publisher
    ..Finally, we show that metformin profoundly inhibits hepatocyte protein synthesis in a manner that is largely dependent on its ability to suppress mTORC1 signaling. ..
  6. Manning B, Toker A. AKT/PKB Signaling: Navigating the Network. Cell. 2017;169:381-405 pubmed publisher
    ..Improved understanding of the molecular wiring of the AKT signaling network continues to make an impact that cuts across most disciplines of the biomedical sciences. ..
  7. Ben Sahra I, Manning B. mTORC1 signaling and the metabolic control of cell growth. Curr Opin Cell Biol. 2017;45:72-82 pubmed publisher
  8. Manning B. Balancing Akt with S6K: implications for both metabolic diseases and tumorigenesis. J Cell Biol. 2004;167:399-403 pubmed
    ..These findings form a novel basis for improved understanding of the pathophysiology of metabolic diseases (e.g., diabetes and obesity), tumor syndromes (e.g., tuberous sclerosis complex and Peutz-Jegher's syndrome), and human cancers. ..
  9. Hallett J, Manning B. CASTORing New Light on Amino Acid Sensing. Cell. 2016;165:15-17 pubmed publisher
    ..In this issue of Cell, Chantranupong et al. identify CASTOR1 as a direct arginine sensor that acts through the GATOR2 complex to regulate mTORC1. ..

More Information


  1. Hoxhaj G, Hughes Hallett J, Timson R, Ilagan E, Yuan M, Asara J, et al. The mTORC1 Signaling Network Senses Changes in Cellular Purine Nucleotide Levels. Cell Rep. 2017;21:1331-1346 pubmed publisher
    ..Our findings suggest that nucleotide sensing, like amino acid sensing, enables mTORC1 to tightly coordinate nutrient availability with the synthesis of macromolecules, such as protein and nucleic acids, produced from those nutrients. ..
  2. Manning B, Logsdon M, Lipovsky A, Abbott D, Kwiatkowski D, Cantley L. Feedback inhibition of Akt signaling limits the growth of tumors lacking Tsc2. Genes Dev. 2005;19:1773-8 pubmed
    ..This study demonstrates that attenuation of the PI3K-Akt pathway in tumors lacking TSC2 contributes to their benign nature. ..
  3. Menon S, Dibble C, Talbott G, Hoxhaj G, Valvezan A, Takahashi H, et al. Spatial control of the TSC complex integrates insulin and nutrient regulation of mTORC1 at the lysosome. Cell. 2014;156:771-85 pubmed publisher
    ..These findings provide a unifying mechanism by which independent pathways affecting the spatial recruitment of mTORC1 and the TSC complex to Rheb at the lysosomal surface serve to integrate diverse growth signals. ..
  4. Valvezan A, Turner M, Belaid A, Lam H, Miller S, McNamara M, et al. mTORC1 Couples Nucleotide Synthesis to Nucleotide Demand Resulting in a Targetable Metabolic Vulnerability. Cancer Cell. 2017;32:624-638.e5 pubmed publisher
    ..These findings reveal a metabolic vulnerability downstream of mTORC1 triggered by anabolic imbalance. ..
  5. Kelsey I, Zbinden M, Byles V, Torrence M, Manning B. mTORC1 suppresses PIM3 expression via miR-33 encoded by the SREBP loci. Sci Rep. 2017;7:16112 pubmed publisher
    ..These results demonstrate that PIM3 is induced upon mTORC1 inhibition, with potential implications for the effects of mTORC1 inhibitors in TSC, cancers, and the many other disease settings influenced by aberrant mTORC1 signaling. ..