Cell Death and Metabolism
Cell Death and Metabolism comprises, in addition to the primary Lysosomal Pathways Group, the team Membrane Systems Biology, headed by senior scientist Kenji Maeda
Our research
The Lysosomal Pathways Group is recognized for its original discoveries in the fields of lysosomes, cell death, autophagy and heat shock proteins, its role in the development of advanced technologies for these studies, and its ability to translate biological findings to the clinics. In addition to these key expertise areas, we have during the last years gathered ample expertise in lipid and membrane biology.
The overall aims of our research are:
- To enlighten the role of lysosomal pathways in cancer initiation and progression
- To discover novel cancer biomarkers, therapeutic targets and drugs
- To translate our discoveries to the clinics
- To educate the next generation of innovative and interdisciplinary cancer researchers
In order to achieve these goals, we focus on:
- Composition and trafficking of endosomes, autophagosomes and lysosomes
- Maintenance of lysosomal membrane integrity and repair of damaged membranes
- Anti-cancer activities of cationic amphiphilic drugs
- Lysosomal control of cell division
- Lysosomal control of cellular acid-base balance
- Lysosomal control of metabolic signaling (CIP2A, mTORC1, AMPK, Myc, STAT3)
- Sphingomyelin trafficking
- Continuous development of new methods
- Collaboration with experts from other fields
Ellegaard AM, Nielsen PB, Jäättelä M: Targeting cancer lysosomes with good old cationic amphiphilic drugs. Rev Physiol Biochem Pharmacol in press 2020
Hämälistö S, Stahl J, Favaro E, Yang Q, Liu B, Christoffersen L, Loos B, Guasch C, Joyce JA, Reinheckel T, Barisic M, Jäättelä M: Spatially and temporally defined lysosomal leakage facilitates mitotic chromosome segregation. Nature Commun 2020;11(1):229
Puustinen P, Keldsbo A, Corcelle-Termeau E, Ngoei KRW, Sønder SL, Farkas T, Andersen K, Oakhill JS, Jäättelä M: DNA-dependent protein kinase regulates lysosomal AMP-dependent protein kinase activation and autophagy. Autophagy 2020;16(10):1871-1888
Holland LKK, Nielsen IØ, Maeda K, Jäättelä M: Snapshot: Lysosomal functions. Cell 2020;181(3):748
Anand A, Liu B, Giacobini JD, Maeda K, Rohde M, Jäättelä M: Cell death induced by cationic amphiphilic drugs depends on lysosomal Ca2+ release and cyclic AMP. Mol Cancer Ther 2019;18(9):1602-1614
Liu B, Palmfeldt J, Lin L, Colaco A, Clemmensen KKB, Huang J, Xu F, Liu X, Maeda K, Luo Y, Jäättelä M: STAT3 associates with vacuolar H(+)-ATPase and regulates cytosolic and lysosomal pH. Cell Res 2018;28(10), 996-1012
Ellegaard AM, Dehlendorff C, Vind AC, Anand A, Cederkvist L, Petersen NHT, Nylandsted J, Stenvang J, Mellemgaard A, Østerlind K, Friis S, Jäättelä M: Repurposing cationic amphiphilic antihistamines for cancer treatment. EBioMedicine 2016;9, 130-139
Corcelle-Termeau E, Vindeløv SD, Hämälistö S, Mograbi B, Keldsbo A, Brasen JH, Favaro E, Adam D, Szyniarowski P, Hofman P, Krautwald S, Farkas T, Petersen NH, Rohde M, Linkermann A, Jäättelä M: Excess sphingomyelin disturbs ATG9A trafficking and autophagosome closure. Autophagy 2016;12(5), 833-849
Petersen NH, Olsen OD, Groth-Pedersen L, Ellegaard AM, Bilgin M, Redmer S, Ostenfeld MS, Ulanet D, Dovmark TH, Lønborg A, Vindeløv SD, Hanahan D, Arenz C, Ejsing CS, Kirkegaard T, Rohde M, Nylandsted J, Jäättelä M: Transformation-associated changes in sphingolipid metabolism sensitize cells to lysosomal cell death induced by inhibitors of acid sphingomyelinase. Cancer Cell 2013;24(3), 379-393
Kirkegaard T, Roth AG, Petersen NH, Mahalka AK, Olsen OD, Moilanen I, Zylicz A, Knudsen J, Sandhoff K, Arenz C, Kinnunen PK, Nylandsted J, Jäättelä M: Hsp70 stabilizes lysosomes and reverts Niemann-Pick disease-associated lysosomal pathology. Nature 2010;463(7280), 549-553
Group leader: Marja Jäättelä
Marja Jäättelä is head of Cell Death and Metabolism - Lysosomal Pathways and director of the Center for Autophagy, Recycling and Disease at the Danish Cancer Society Research Center as well as professor of Cell Death and Metabolism at the Copenhagen University. She is elected member of the European Molecular Biology Organization (EMBO), Danish Royal Academy of Sciences and Finnish Academy Science and Letters and serves in numerous international scientific advisory boards, editorial boards and evaluation panels.
Dr. Jäättelä’s main research interests include the role of lysosomes and autophagy in cancer progression, alternative cell death pathways, maintenance of lysosomal membrane integrity, lipid metabolism and lipid storage disorders.
The translational part of Dr. Jäättelä’s present research focuses on developing clinically relevant acid sphingomyelinase inhibiting cationic amphiphilic drugs for cancer treatment.
ORCID: 0000-0001-5950-7111
Key funding
Danish National Research Foundation
Novo Nordisk Foundation
Danish Cancer Society
Membrane Systems Biology
Human cells combine thousands of different lipids to construct the diverse cellular membranes with each their properties and functionalities.
We investigate architecture of human cells, and how it is altered in cancers with focus on these membrane lipids. To achieve this, we combine mass spectrometry-based lipidomics and in-house developed methods of systematic purification of diverse cellular compartments.
Our goal is to identify key regulatory mechanisms in the metabolism and transport of lipids essential for cancer pathophysiology and to exploit them in therapeutic strategies.
Nielsen IØ, Groth-Pedersen L, Dicroce-Giacobini J, Jonassen ASH, Mortensen M, Bilgin M, Schmiegelow K, Jäättelä M, Maeda K: Cationic amphiphilic drugs induce elevation in lysoglycerophospholipid levels and cell death in leukemia cells. Metabolomics 2020;16(9):91
Holland LKK, Nielsen IØ, Maeda K, Jäättelä M: Snapshot: Lysosomal functions. Cell 2020;181(3):748
Nielsen IØ, Vidas Olsen A, Dicroce-Giacobini J, Papaleo E, Andersen KK, Jäättelä M, Maeda K, Bilgin M: Comprehensive Evaluation of a Quantitative Shotgun Lipidomics Platform for Mammalian Sample Analysis on a High-Resolution Mass Spectrometer. J Am Soc Mass Spectrom 2020;31(4):894-907
Bilgin M, Nylandsted J, Jäättelä M, Maeda K: Quantitative profiling of lysosomal lipidome by shotgun lipidomics. Methods Mol.Biol 2017;1594:19-34
Maeda K, Poletto M, Chiapparino A, Gavin AC: A generic protocol for the purification and characterization of water-soluble complexes of affinity-tagged proteins and lipids. Nat Protoc 2014;9(9):2256-2266
Maeda K, Anand K, Chiapparino A, Kumar A, Poletto M, Kaksonen M, Gavin AC: Interactome map uncovers phosphatidylserine transport by oxysterol-binding proteins. Nature 2013;501(7466):257-261
Team leader: Kenji Maeda
Kenji Maeda has done his PhD at the Technical University of Denmark 2007, whereafter he became a postdoctoral fellow at EMBL Heidelberg 2008-2014.
ORCID: 0000-0002-9080-5691