Susanne Schlisio Group
The research in our group concerns the mechanisms of how disruption of oxygen-sensing pathways can lead to cancer.
Oxygen-sensing and cancer
Our research concerns the mechanisms of how disruption of oxygen-sensing pathways can lead to cancer. Oxygen sensors enable the cell to adapt to low-oxygen environments and are critical for normal development and apoptosis. These events are often disrupted in the development of tumors. Oxygen sensing is mediated partly via prolyl hydroxylases that require molecular oxygen for enzymatic activity. Our work focuses on how prolyl hydroxylases execute apoptosis in neural precursors during development and how disruption of this process can lead to certain forms of nervous-system tumors.
Single-nuclei transcriptomes from human adrenal gland reveal distinct cellular identities of low and high-risk neuroblastoma tumors.
Bedoya-Reina OC, Li W, Arceo M, Plescher M, Bullova P, Pui H, Kaucka M, Kharchenko P, Martinsson T, Holmberg J, Adameyko I, Deng Q, Larsson C, Juhlin CC, Kogner P, Schlisio S.
Nat Commun. 2021 Sep 7;12(1):5309. doi: 10.1038/s41467-021-24870-7.
Aberrant splicing in neuroblastoma generates RNA-fusion transcripts and provides vulnerability to spliceosome inhibitors.
Shi Y, Yuan J, Rraklli V, Maxymovitz E, Cipullo M, Liu M, Li S, Westerlund I, Bedoya-Reina OC, Bullova P, Rorbach J, Juhlin CC, Stenman A, Larsson C, Kogner P, O'Sullivan MJ, Schlisio S, Holmberg J.
Nucleic Acids Res. 2021 Mar 18;49(5):2509-2521. doi: 10.1093/nar/gkab054.
Chromaffin Cells with Sympathoblast Signature: Too Similar to Keep Apart?
Bedoya-Reina OC, Schlisio S.
Cancer Cell. 2021 Feb 8;39(2):134-135. doi: 10.1016/j.ccell.2020.12.009. Epub 2020 Dec 31.
EglN3 hydroxylase stabilizes BIM-EL linking VHL type 2C mutations to pheochromocytoma pathogenesis and chemotherapy resistance.
Li S, Rodriguez J, Li W, Bullova P, Fell SM, Surova O, et al
Proc. Natl. Acad. Sci. U.S.A. 2019 Aug;116(34):16997-17006
PHD3 Regulates p53 Protein Stability by Hydroxylating Proline 359.
Rodriguez J, Herrero A, Li S, Rauch N, Quintanilla A, Wynne K, et al
Cell Rep 2018 07;24(5):1316-1329
Combined epigenetic and differentiation-based treatment inhibits neuroblastoma tumor growth and links HIF2α to tumor suppression.
Westerlund I, Shi Y, Toskas K, Fell SM, Li S, Surova O, et al
Proc. Natl. Acad. Sci. U.S.A. 2017 07;114(30):E6137-E6146
Neuroblast differentiation during development and in neuroblastoma requires KIF1Bβ-mediated transport of TRKA.
Fell SM, Li S, Wallis K, Kock A, Surova O, Rraklli V, et al
Genes Dev. 2017 05;31(10):1036-1053
The 1p36 Tumor Suppressor KIF 1Bβ Is Required for Calcineurin Activation, Controlling Mitochondrial Fission and Apoptosis.
Li S, Fell SM, Surova O, Smedler E, Wallis K, Chen ZX, et al
Dev. Cell 2016 Jan;36(2):164-78
The 2-oxoglutarate analog 3-oxoglutarate decreases normoxic hypoxia-inducible factor-1α in cancer cells, induces cell death, and reduces tumor xenograft growth.
Koivunen P, Fell SM, Lu W, Rabinowitz JD, Kung AL, Schlisio S
Hypoxia (Auckl) ;4():15-27
XAF1 promotes neuroblastoma tumor suppression and is required for KIF1Bβ-mediated apoptosis.
Choo Z, Koh RY, Wallis K, Koh TJ, Kuick CH, Sobrado V, et al
Oncotarget 2016 Jun;7(23):34229-39
RNA helicase A is a downstream mediator of KIF1Bβ tumor-suppressor function in neuroblastoma.
Chen ZX, Wallis K, Fell SM, Sobrado VR, Hemmer MC, Ramsköld D, et al
Cancer Discov 2014 Apr;4(4):434-51
Mutation analysis of HIF prolyl hydroxylases (PHD/EGLN) in individuals with features of phaeochromocytoma and renal cell carcinoma susceptibility.
Astuti D, Ricketts CJ, Chowdhury R, McDonough MA, Gentle D, Kirby G, et al
Endocr. Relat. Cancer 2011 Feb;18(1):73-83
Neuronal apoptosis by prolyl hydroxylation: implication in nervous system tumours and the Warburg conundrum.
J. Cell. Mol. Med. 2009 Oct;13(10):4104-12
The kinesin KIF1Bbeta acts downstream from EglN3 to induce apoptosis and is a potential 1p36 tumor suppressor.
Schlisio S, Kenchappa RS, Vredeveld LC, George RE, Stewart R, Greulich H, et al
Genes Dev. 2008 Apr;22(7):884-93
VHL loss actuates a HIF-independent senescence programme mediated by Rb and p400.
Young AP, Schlisio S, Minamishima YA, Zhang Q, Li L, Grisanzio C, et al
Nat. Cell Biol. 2008 Mar;10(3):361-9
pVHL acts as an adaptor to promote the inhibitory phosphorylation of the NF-kappaB agonist Card9 by CK2.
Yang H, Minamishima YA, Yan Q, Schlisio S, Ebert BL, Zhang X, et al
Mol. Cell 2007 Oct;28(1):15-27
Neuronal apoptosis linked to EglN3 prolyl hydroxylase and familial pheochromocytoma genes: developmental culling and cancer.
Lee S, Nakamura E, Yang H, Wei W, Linggi MS, Sajan MP, et al
Cancer Cell 2005 Aug;8(2):155-67
Research group leader
Susanne SchlisioPhD, Associate Professor
Susanne Schlisio is a cancer biologist with extensive experience in sympathoadrenal nervous system malignancies, neuronal development and cancer mouse models. She performed her PhD studies at Duke University Medical School in 2002 in cancer research. In 2008, she completed her postdoctoral research at the Dana Farber Cancer Institute at the Harvard Medical School. As a postdoctoral researcher in the laboratory of Dr. William G. Kaelin, Jr. she was part of the team discovering how cells adapt to changes in oxygen availability and how this process is directly linked to cancer-discoveries that now have been recognized with award of the Nobel Prize to Dr. Kaelin. In 2008, she was a recipient of an internationally competitive member position at the Ludwig Cancer Institute Stockholm to start her own research group. Since 2017, she is faculty at Department of Microbiology Tumor and Cell biology at Karolinska Institutet, Stockholm. Her current and future work includes the identification of novel oxygen-sensing pathways that are implicated in malignant transformation, with focus on cancer arising from the sympathoadrenal lineage, such as neuroblastoma and pheochromocytoma.
Laboratory at Ludwig Cancer Research
- H2020 European Research Commission ERC-2019-SyG
- Knut och Alice Wallenbergs Stiftelse
- Swedish Research Council (VR)
- Swedish Childhood Cancer Foundation (BCF)
- Swedish Cancer Society (CF)
- Para Difference Foundation
- Gösta Fraenckels stiftelse för medicinsk forskning