Cell Death and Metabolism

Cell Death and Metabolism comprises, in addition to the primary Lysosomal Pathways Group, one team:

Membrane Systems Biology team headed by senior scientist Kenji Maeda

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

Selected Publications:

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