Susanne Schlisio

PhD, Associate Professor Susanne Schlisio
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.

More information about my research can be found at: Susanne Schlisio lab:
https://ki.se/en/onkpat/schlisio-lab

2019 H2020 European Research Commission ERC-2019-SyG
2017 Senior Research Position from the Swedish Cancer Foundation.
2008 Recipient of an internationally competitive member position at the Ludwig Cancer Institute
2008 Friends for Life Dana Farber Award, USA
2008 Melanoma Research Award MRF, USA
2007 Friends of Dana Farber Award, USA
2007 Charles H. Hood Child Health Research Award, USA
2006 VHL Family Alliance Research Award, USA
2006 Charles A. King Trust Postdoctoral Research Fellowship USA
2002: PhD, Duke University Medical School, Durham, N.C., USA, 2002
1999: MSc, Humboldt University, Berlin, Germany

*Oxygen Sensing and Cancer*
How do we cope with oxygen deprivation (hypoxia) in health and disease?

Oxygen sensors enable the cell to adapt to low-oxygen environments and drive metabolic adaptation, but are also critical for normal development and apoptosis. Hypoxia is a hallmark of cardiovascular disease and cancer, which are the leading causes of death worldwide. Our research concerns the mechanisms of how alterations in oxygen-sensing pathways can lead to cancer. We are interested how we adapt to hypoxia at the cellular level, and using that knowledge to combat diseases, such as cancer. Oxygen sensing is mediated partly via prolyl hydroxylases that require
molecular oxygen for enzymatic activity. Our work focuses on 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.

*Exploring drivers of intratumor heterogeneity and phenotypic plasticity*
Why are advanced cancers eventually acquiring resistance to targeted therapies and relapse?

Acquired resistance is the direct consequence of pre-existing intratumor heterogeneity. Systematic characterization of dynamic properties of intratumor heterogeneity and phenotypic plasticity can guide treatment strategies and improve clinical outcome for cancer patients. Currently, our laboratory developed a new analytic and experimental approach based on single nuclei transcriptomics and mass spectrometry to explore intra-tumor heterogeneity and plasticity in childhood neuroblastoma and pheochromocytoma. We generated novel tumor mouse model systems and include human tumors to perform comparative differentiation trajectory analysis, to make predictions and, finally, to perform preliminary validations of
envisioned tumor differentiation strategies. We are exploring embryonic cell state transitions during sympatho-adrenal development that enables us to identify non-mutational drivers of intratumor heterogeneity.

*Exploring clinical heterogeneity and outcome in high-risk childhood neuroblastoma*

Childhood neuroblastoma has a remarkable variability in outcome. Age at diagnosis is one of the most important prognostic factors, with children less than 1 year old having favorable outcomes. We study single-cell and single-nuclei transcriptomes of neuroblastoma with
different clinical risk groups and stages, including healthy adrenal gland. We compare tumor cell populations with embryonic mouse sympatho-adrenal derivatives, and post-natal human adrenal gland. We provide evidence that low and high-risk neuroblastoma have different cell identities, representing two disease entities. Low-risk neuroblastoma presents a transcriptome that resembles sympatho- and chromaffin cells, whereas malignant cells enriched in high-risk neuroblastoma resembles a subtype of TRKB+ cholinergic progenitor population identified in human post-natal gland. Analyses of these populations reveal different gene expression programs for worst and better survival in correlation with age at diagnosis. Our findings reveal two cellular identities and a composition of human neuroblastoma tumors reflecting clinical heterogeneity and outcome.

More information about my research can be found at: Susanne Schlisio lab:
https://ki.se/en/onkpat/schlisio-lab

-------- Our methods ---------------------------------------------------------
.... Imaging
* RNA scope, IHC,
* Spatial techniques: In Situ Sequencing (ISS) in collaboration with Mats
Nilson lab at Scilife
.... Bioinformatics
* Single nuclei RNAseq
* RNA velocity to explore trajectory analysis during tumor progression
* Proteomics analyses by nanoLC-MS/MS
.... Tumor mouse models
* Generating novel neuroblastoma and pheochromocytoma mouse models
* Lineage tracing
.... Biochemistry
* Hydroxylation assays
* Intro translation
* S35 capture pulldowns
* Seahorse to study mitochondrial metabolism
* shRNA and CRISPR/Cas9 lentiviral transduction

-------- Single Cell Resources -----------------------------------------------
Explore deep-sequence full-length coverage RNA from single cell and nuclei of the post-natal human gland, of postnatal mouse adrenal gland and
of human neuroblastoma tumors across different risk groups:
http://oxygen.mtc.ki.se/nc_nb_2021.html

Single Cell Resources [1]
[1] https://oxygen.mtc.ki.se/nc_nb_2021.html

More information about my research can be found at: Susanne Schlisio lab:
https://ki.se/en/onkpat/schlisio-lab