E
Ellen Triantafellow
Researcher at Novartis
Publications - 13
Citations - 5037
Ellen Triantafellow is an academic researcher from Novartis. The author has contributed to research in topics: Autophagy & PI3K/AKT/mTOR pathway. The author has an hindex of 8, co-authored 13 publications receiving 4491 citations.
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Journal ArticleDOI
Bidirectional Transport of Amino Acids Regulates mTOR and Autophagy
Paul Nicklin,Philip Bergman,Bailin Zhang,Ellen Triantafellow,Henry Wang,Beat Nyfeler,Haidi Yang,Marc Hild,Charles Kung,Christine D. Wilson,Vic E. Myer,Jeffrey P. MacKeigan,Jeffrey A. Porter,Y. Karen Wang,Lewis C. Cantley,Peter Finan,Leon Murphy +16 more
TL;DR: It is shown that cellular uptake of L-glutamine and its subsequent rapid efflux in the presence of essential amino acids (EAA) is the rate-limiting step that activates mTOR.
Journal ArticleDOI
Activation of a Metabolic Gene Regulatory Network Downstream of mTOR Complex 1
Katrin Düvel,Jessica L. Yecies,Suchithra Menon,Pichai Raman,Alex Lipovsky,Amanda Souza,Ellen Triantafellow,Qicheng Ma,Regina Gorski,Stephen Cleaver,Matthew G. Vander Heiden,Jeffrey P. MacKeigan,Peter Finan,Clary B. Clish,Leon Murphy,Brendan D. Manning +15 more
TL;DR: It is demonstrated that mTORC1 activation is sufficient to stimulate specific metabolic pathways, including glycolysis, the oxidative arm of the pentose phosphate pathway, and de novo lipid biosynthesis, through the activation of a transcriptional program affecting metabolic gene targets of hypoxia-inducible factor and sterol regulatory element-binding protein.
Activation of a Metabolic Gene Regulatory Network Downstream of mTOR Complex 1
Katrin Düvel,Jessica L. Yecies,Suchithra Menon,Pichai Raman,Ellen Triantafellow,Qicheng Ma,Regina Gorski,Stephen Cleaver,Jeffrey P. MacKeigan,Peter Finan,Leon Murphy,Brendan D. Manning,Alex Lipovsky,Amanda Souza,Matthew G. Vander Heiden,Clary B. Clish +15 more
Abstract: Aberrant activation of the mammalian target of rapamycin complex 1 (mTORC1) is a common molecular event in a variety of pathological settings, including genetic tumor syndromes, cancer, and obesity. However, the cell-intrinsic consequences of mTORC1 activation remain poorly defined. Through a combination of unbiased genomic, metabolomic, and bioinformatic approaches, we demonstrate that mTORC1 activation is sufficient to stimulate specific metabolic pathways, including glycolysis, the oxidative arm of the pentose phosphate pathway, and de novo lipid biosynthesis. This is achieved through the activation of a transcriptional program affecting metabolic gene targets of hypoxia-inducible factor (HIF1alpha) and sterol regulatory element-binding protein (SREBP1 and SREBP2). We find that SREBP1 and 2 promote proliferation downstream of mTORC1, and the activation of these transcription factors is mediated by S6K1. Therefore, in addition to promoting protein synthesis, mTORC1 activates specific bioenergetic and anabolic cellular processes that are likely to contribute to human physiology and disease.
Journal ArticleDOI
Selective VPS34 inhibitor blocks autophagy and uncovers a role for NCOA4 in ferritin degradation and iron homeostasis in vivo
William E. Dowdle,Beat Nyfeler,Jane Nagel,Robert Elling,Shanming Liu,Ellen Triantafellow,Suchithra Menon,Zuncai Wang,Ayako Honda,Gwynn Pardee,John Cantwell,Catherine Luu,Ivan Cornella-Taracido,Edmund Harrington,Peter Fekkes,Hong Lei,Qing Fang,Mary Ellen Digan,Debra Burdick,Andrew F. Powers,Stephen B. Helliwell,Simon D’Aquin,Julie Bastien,Henry Wang,Dmitri Wiederschain,Jenny Kuerth,Philip Bergman,David Schwalb,Jason R. Thomas,Savuth Ugwonali,Fred Harbinski,John A. Tallarico,Christine D. Wilson,Vic E. Myer,Jeffery A. Porter,Dirksen E. Bussiere,Peter Finan,Mark Labow,Xiaohong Mao,Lawrence G. Hamann,Brendan D. Manning,Reginald Valdez,Thomas B. Nicholson,Markus Schirle,Mark Knapp,Erin P. Keaney,Leon Murphy +46 more
TL;DR: a4−/− mice exhibit a profound accumulation of iron in splenic macrophages, which are critical for the reutilization of iron from engulfed red blood cells, and a previously unappreciated role for autophagy and NCOA4 in the control of iron homeostasis in vivo is revealed.
Journal ArticleDOI
Relieving Autophagy and 4EBP1 from Rapamycin Resistance
Beat Nyfeler,Philip Bergman,Ellen Triantafellow,Christine D. Wilson,Yanyi Zhu,Branko Radetich,Peter Finan,Daniel J. Klionsky,Leon Murphy +8 more
TL;DR: It is shown that the ability of rapamycin to activate autophagy in different cell lines correlates with mTORC1 stability and that knockdown of raptor relieves Autophagy and the eIF4E effector pathway fromRapamycin resistance.