Lysosomal Pathways

Unit leader: Marja Jäättelä

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
Marja Jäättelä

Marja Jäättelä

Marja Jäättelä is head of the Cell Death and Metabolism Unit 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.

Selected Publications:

Liu, B., Palmfeldt, J., Lin, L., Colaco, A., Clemmensen, K. K. B., 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, A. M., Dehlendorff, C., Vind, A. C., Anand, A., Cederkvist, L., Petersen, N. H. T., 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, S. D., Hämälistö, S., Mograbi, B., Keldsbo, A., Brasen, J. H., Favaro, E., Adam, D., Szyniarowski, P., Hofman, P., Krautwald, S., Farkas, T., Petersen, N. H., Rohde, M., Linkermann, A., Jäättelä, M.
Excess sphingomyelin disturbs ATG9A trafficking and autophagosome closure.
Autophagy. 2016: 12(5), 833-849

Puustinen, P., Rytter, A., Mortensen, M., Kohonen, P., Moreira, J. M., Jäättelä, M.
CIP2A oncoprotein controls cell growth and autophagy through mTORC1 activation.
J.Cell Biol. 2014: 204(5), 713-727

Kirkegaard, T., Gray, J., Priestman, D. A., Wallom, K. L., Atkins, J., Olsen, O. D., Klein, A., Drndarski, S., Petersen, N. H., Ingemann, L., Smith, D. A., Morris, L., Bornæs, C., Jorgensen, S. H., Williams, I., Hinsby, A., Arenz, C., Begley, D., Jäättelä, M., Platt, F. M.
Heat shock protein-based therapy as a potential candidate for treating the sphingolipidoses.
Sci.Transl.Med. 2016: 8(355), 355ra118

Aits, S., Kricker, J., Liu, B., Ellegaard, A. M., Hämälistö, S., Tvingsholm, S., Corcelle-Termeau, E., Høgh, S., Farkas, T., Holm, Jonassen A., Gromova, I., Mortensen, M., Jäättelä, M.
Sensitive detection of lysosomal membrane permeabilization by lysosomal galectin puncta assay.
Autophagy. 2015: 11(8), 1408-1424

Petersen, N. H., Olsen, O. D., Groth-Pedersen, L., Ellegaard, A. M., Bilgin, M., Redmer, S., Ostenfeld, M. S., Ulanet, D., Dovmark, T. H., Lønborg, A., Vindeløv, S. D., Hanahan, D., Arenz, C., Ejsing, C. S., 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, A. G., Petersen, N. H., Mahalka, A. K., Olsen, O. D., Moilanen, I., Zylicz, A., Knudsen, J., Sandhoff, K., Arenz, C., Kinnunen, P. K., Nylandsted, J., Jäättelä, M.
Hsp70 stabilizes lysosomes and reverts Niemann-Pick disease-associated lysosomal pathology.
Nature 2010: 463(7280), 549-553

ORCID:

Marja Jäättelä

0000-0001-5950-7111