Anders Mutvei research group
Our laboratory is focused on characterizing the essential signaling and metabolic processes that tumor cells hijack and reprogram to promote tumorigenesis and drug resistance. We are particularly interested in understanding the role of lysosomes in these processes. Our long-term goal is to translate this knowledge into lysosome-based pharmacological remedies for the clinic.
Lysosomes are catabolic endosomes that break down macromolecules. Due to this function, they were historically perceived as mere “housekeeping” organelles responsible for disposing of macromolecular waste. However, over the past decade, it has become increasingly evident that lysosomes have critical roles beyond degradation, which frequently becomes dysregulated in tumors. This includes controlling the cellular synthesis of new biomolecules - processes which tumor cells need to rewire in order to grow and survive.
In our lab, we investigate how tumor-associated changes in the lysosomal pool affect tumor metabolism, aggressiveness and resistance to therapies. We are particularly interested in the fact that tumor cells often display abnormally increased levels of lysosomes, and to characterize how this drives disease progression. Our work employs cutting-edge imaging techniques, large-scale omics approaches (proteomics, metabolomics, etc.), and classical biochemical methods.
Research group leader Anders Mutvei
We are increadibly greatful for the support from: Cancerfonden, Vetenskapsrådet, Åke Wibergs Stiftelse, Magnus Bergvalls stiftelse, Stiftelsen Lars Hiertas minne.
Biomedical Analytics programme
Balancing lysosome abundance in health and disease.
Mutvei AP, Nagiec MJ, Blenis J
Nat Cell Biol 2023 Aug;():
An affinity tool for the isolation of endogenous active mTORC1 from various cellular sources.
Ibrahim YH, Pantelios S, Mutvei AP
J Biol Chem 2023 May;299(5):104644
Prolonged deprivation of arginine or leucine induces PI3K/Akt-dependent reactivation of mTORC1.
Buel GR, Dang HQ, Asara JM, Blenis J, Mutvei AP
J Biol Chem 2022 Jun;298(6):102030
Altered propionate metabolism contributes to tumour progression and aggressiveness.
Gomes AP, Ilter D, Low V, Drapela S, Schild T, Mullarky E, Han J, Elia I, Broekaert D, Rosenzweig A, Nagiec M, Nunes JB, Schaffer BE, Mutvei AP, Asara JM, Cantley LC, Fendt SM, Blenis J
Nat Metab 2022 Apr;4(4):435-443
Rap1-GTPases control mTORC1 activity by coordinating lysosome organization with amino acid availability.
Mutvei AP, Nagiec MJ, Hamann JC, Kim SG, Vincent CT, Blenis J
Nat Commun 2020 Mar;11(1):1416
Age-induced accumulation of methylmalonic acid promotes tumour progression.
Gomes AP, Ilter D, Low V, Endress JE, Fernández-García J, Rosenzweig A, Schild T, Broekaert D, Ahmed A, Planque M, Elia I, Han J, Kinzig C, Mullarky E, Mutvei AP, Asara J, de Cabo R, Cantley LC, Dephoure N, Fendt SM, Blenis J
Nature 2020 Sep;585(7824):283-287
Dynamic Incorporation of Histone H3 Variants into Chromatin Is Essential for Acquisition of Aggressive Traits and Metastatic Colonization.
Gomes AP, Ilter D, Low V, Rosenzweig A, Shen ZJ, Schild T, Rivas MA, Er EE, McNally DR, Mutvei AP, Han J, Ou YH, Cavaliere P, Mullarky E, Nagiec M, Shin S, Yoon SO, Dephoure N, Massagué J, Melnick AM, Cantley LC, Tyler JK, Blenis J
Cancer Cell 2019 Oct;36(4):402-417.e13
Regulation of GSK3 cellular location by FRAT modulates mTORC1-dependent cell growth and sensitivity to rapamycin.
He L, Fei DL, Nagiec MJ, Mutvei AP, Lamprakis A, Kim BY, Blenis J
Proc Natl Acad Sci U S A 2019 Sep;116(39):19523-19529
Notch signaling promotes a HIF2α-driven hypoxic response in multiple tumor cell types.
Mutvei AP, Landor SK, Fox R, Braune EB, Tsoi YL, Phoon YP, Sahlgren C, Hartman J, Bergh J, Jin S, Lendahl U
Oncogene 2018 Nov;37(46):6083-6095