Susanne Schlisio

About me

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 completed her PhD studies at Duke University Medical School in 2002 in cancer research and her postdoctoral research at the Dana Farber Cancer Institute at the Harvard Medical School in 2008. 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 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. Her 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. Her lab generated novel tumor mouse model systems and includes human tumors to perform comparative differentiation trajectory analysis, to make predictions and, finally, to perform preliminary validations of envisioned tumor differentiation strategies.

 

Research description

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 acquire 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.

Methods we use

Imaging: 

• RNA scope
• 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

 

Education

2002: PhD, Duke University Medical School, Durham, N.C., USA, 2002

1999: MSc, Humboldt University, Berlin, Germany