Susanne Schlisio

Susanne Schlisio

Senior Lecturer | Docent

Lineage plasticity, tumor heterogeneity, and metastasis in neuroblastoma and paraganglioma

Telephone: +46852487117
Visiting address: BioClincium, Visionsgatan 4, våning 6, 17164 Solna
Postal address: K7 Onkologi-Patologi, K7 Forskning Schlisio, 171 77 Stockholm
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About me

  • PhD, Associate Professor Susanne Schlisio

    Susanne Schlisio is a cancer biologist and Associate Professor at Karolinska Institutet with expertise in developmental cancer biology, tumor plasticity, and sympathoadrenal nervous system malignancies. Her research focuses on how developmental programs contribute to tumor heterogeneity, malignant progression, metastasis, and therapy resistance.

    She obtained her PhD in cancer research from Duke University School of Medicine in 2002 and completed postdoctoral training at the Dana-Farber Cancer Institute and Harvard Medical School in 2008.

    During her postdoctoral studies in the laboratory of William G. Kaelin Jr., she was part of the research team that contributed to the discovery of how cells sense and adapt to changes in oxygen availability and how dysregulation of oxygen-sensing pathways contributes to cancer development. These discoveries were later recognized with the Nobel Prize in Physiology or Medicine awarded to Dr. Kaelin.

    In 2008, she was recruited through an internationally competitive investigator position to establish an independent research group at Ludwig Cancer Research. Since 2017, she has been faculty at Karolinska Institutet.

    Her current research focuses on cancers arising from the sympathoadrenal lineage, including neuroblastoma and pheochromocytoma/paraganglioma (PPGL). Her laboratory investigates how embryonic developmental programs and lineage plasticity shape tumor evolution and intratumoral heterogeneity. By integrating analyses of human tumors with advanced mouse models, lineage tracing, and advanced single-cell and spatial transcriptomic technologies, her group aims to identify novel mechanisms underlying malignant cell-state transitions and to develop differentiation-based therapeutic strategies for aggressive childhood and endocrine cancers.

    Selected Honors and Competitive Research Funding

    2026-2028 Paradifference Foundation research funding
    2026-2028 Swedish Cancer Society (Cancerfonden) Project Grant
    2025-2027 Swedish Childhood Cancer Foundation (Barncancerfonden) Project Grant
    2023-2028 Swedish Research Council (VR) Project Grant
    2019-2026 European Research Council (ERC) Synergy Grant
    2017 Senior Research Position, Swedish Cancer Foundation
    2008 Internationally competitive investigator position, Ludwig Cancer Research

Research

  • Developmental lineage plasticity in sympathoadrenal cancers

    The sympathoadrenal lineage gives rise to neuroblastoma and pheochromocytoma/paraganglioma (PPGL), tumors that display remarkable cellular heterogeneity and divergent clinical behavior. Our laboratory investigates how developmental programs, lineage plasticity, and cell-state transitions contribute to tumor initiation, progression, metastasis, and therapy resistance.

    We combine genetically engineered mouse models, lineage tracing, single-cell and spatial transcriptomics, proteomics, and computational trajectory analysis to study how malignant cells re-activate embryonic developmental programs during tumor evolution. By integrating analyses of human tumors with developmental reference atlases and experimental model systems, we aim to identify non-mutational mechanisms driving intratumoral heterogeneity and aggressive disease states.

    A major focus of our work is to understand how chromaffin, sympathoblast, neural crest-derived progenitor, and transitional cell states contribute to tumor evolution and treatment resistance in neuroblastoma and PPGL.

    Tumor heterogeneity and cell-state transitions in neuroblastoma

    High-risk neuroblastoma remains one of the most lethal childhood cancers and exhibits substantial inter- and intratumoral heterogeneity. Our laboratory investigates how developmental cell identities and tumor plasticity influence clinical outcome and therapeutic response.

    Using single-cell and spatial multi-omics approaches, we compare tumor cell populations across neuroblastoma risk groups with embryonic and postnatal sympathoadrenal cell states. Our studies revealed distinct cellular identities associated with low-risk versus high-risk disease and identified developmental transcriptional programs linked to poor clinical outcome.

    Current work focuses on understanding how dynamic lineage transitions, developmental timing, and microenvironmental interactions contribute to malignant progression and resistance to therapy.

    Oxygen sensing, metabolism, and endocrine tumor biology

    Our research also investigates how oxygen-sensing and metabolic pathways regulate cellular differentiation and tumor biology. Building on earlier work identifying mechanisms of cellular adaptation to hypoxia, we study how metabolic stress and mitochondrial dysfunction influence endocrine tissue homeostasis, developmental plasticity, and malignant transformation.

    We are particularly interested in how oxygen-sensing pathways intersect with lineage specification and cell-state regulation in neuroendocrine tumors arising from the sympathoadrenal system.

    Experimental and Computational Approaches

    Our laboratory integrates experimental cancer biology with advanced genomics and computational approaches, including:

    Single-cell and spatial multi-omics

    • Single-cell and single-nucleus RNA sequencing
    • Spatial transcriptomics and in situ sequencing
    • RNA velocity and developmental trajectory analysis
    • Comparative developmental atlasing
    • Proteomics and metabolic profiling

    Experimental model systems

    • Genetically engineered mouse models of neuroblastoma and PPGL
    • Lineage tracing approaches
    • Human tumor and adrenal tissue analyses
    • CRISPR/Cas9 and lentiviral perturbation systems

    Imaging and molecular pathology

    • RNAscope and immunohistochemistry
    • Spatially resolved transcriptomic technologies
    • Tumor ecosystem and microenvironment analysis

Teaching

  • Susanne Schlisio is Associate Professor and group leader at Karolinska Institutet with extensive experience in teaching and supervision within cancer biology, molecular medicine, and experimental oncology. Her teaching focuses particularly on tumor biology, developmental biology, cellular plasticity, precision medicine, and modern genomic and transcriptomic technologies, including single-cell and spatial transcriptomics.

    She teaches at undergraduate, advanced, and doctoral levels within medical, master’s, and PhD education programs, and supervises doctoral students, postdoctoral fellows, and degree project students. Her pedagogical work aims to integrate fundamental biological mechanisms with clinically relevant questions in cancer research.

Articles

All other publications

Grants

  • Barncancerfonden
    1 January 2025 - 31 December 2025
  • Barncancerfonden
    1 January 2024 - 31 December 2024
  • Swedish Research Council
    1 December 2023 - 30 November 2028
    Acquired cancer therapy resistance is the direct consequence of pre-existing intratumor heterogeneity. Intratumor heterogeneity is a hallmark of high-risk pediatric neuroblastoma (NB) which underpins dismal prognosis and treatment outcomes. Apart from a well-recognized “genetic mosaicism”, when tumors are comprised of several clones with distinct mutations, neuroblastomas have recently been shown to exhibit striking phenotypic drift upon treatment and changes in local microenvironment. Denoted as “tumor plasticity”, the latter phenomenon does not appear to stem from de novo genetic mutations but is rather driven by complex transcriptional rearrangements in neuroblastoma cells triggered by still poorly understood signaling clues. Phenotypic plasticity thus comprises a new dimension of intratumor heterogeneity, mechanisms of which need to be properly understood to develop more efficient treatments. Here we introduce a analytic approach based on space-resolved single nuclei transcriptomics with integrated mass spectrometry on human neuroblastoma and paraganglioma. Our work is supplemented by mechanistic studies in animal neuroblastoma and paraganglioma models, enabling comparative differentiation trajectory analysis and lineage tracing of tumor subpopulations. Collectively, the gained insights should expose the nature of intratumor heterogeneity and phenotypic plasticity in neuroblastoma and paraganglioma, improving prognostication and treatment options for this lethal cancer.
  • Swedish Cancer Society
    1 January 2023
    Neuroblastoma is the most common pediatric solid tumor and is characterized by a high degree of cellular heterogeneity. This heterogeneity may be an underlying cause of the different degrees of the disease as well as the variable response to treatment. Our preliminary data show that neuroblastoma is very heterogeneous in itself and resembles certain stages of neurallist differentiation into sympathetic neuroblast cells. Identification of the origin cell for these sympathetic tumors can be crucial in revealing the causes of disease heterogeneity and clinical behavior. Here we highlight the origin and heterogeneity of pediatric neuroblastomas. We will develop a new analytical and experimental approach based on single-cell transcriptomics to predict promising treatment strategies that take into account tumor heterogeneity. We will use human neuroblastoma tumors and mouse models to develop such a comparative differentiation assay, to make predictions, and finally to perform preliminary validations of strategies to induce tumors to differentiate. Heterogeneity in tumors including the presence of resistant clones represents a major challenge for the treatment of high-risk neuroblastoma (NB). There are currently no treatments that counteract the heterogeneity of the cancer. Classification of bulk tumors and corresponding predictions are too general. The understanding of heterogeneity will provide critical insight into the development of targeted therapeutic strategies. Knowing the pathways and target genes that can drive tumors to less metastatic and more mature conditions can be a key to cancer treatment.
  • Barncancerfonden
    1 January 2021 - 31 December 2021
  • European Research Council
    1 October 2020 - 30 September 2026
    The interactions between tumor and its microenvironment are often critical to uncovering the mechanisms of tumor survival. A striking example is the recent success of immunotherapy approaches that expose tumor cells to immune attack by disrupting a specific interaction between the tumor and infiltrating lymphocytes. The tumor can also repress immune response by inducing complex interactions among dozens of immune and stromal cell types that typically make up tumor microenvironment, however those remain largely uncharacterized as we currently lack systematic approaches to uncover relevant cell-cell interactions. The alternative to killing tumor cells, either directly or through immune system, is to force them to differentiate. Such strategy is particularly promising for tumors arising due to failure of progenitor populations to follow proper differentiation cascade. Here as well, the progress has been limited by lack of understanding of specific intercellular signals that that are disrupted in tumorigenesis. We propose a systematic approach for characterizing cell-cell interactions in complex microenvironments through joint analysis of spatially-resolved and disassociated single-cell transcriptomics. We will apply it to identify inter-cellular signals and pathways that can push tumors of neural crest origin, including as pheochromocytoma (PCC), paraganglioma (PGL) and neuroblastoma (NB), towards terminal differentiation. Building on our expertise with neural crest development, we will use single-cell profiling to map individual tumor cells onto developmental trajectory of neural crest differentiation. Spatial transcriptomics analysis will then be used to identify the sources and nature of microenvironment signals that channel neural crest differentiation during normal development. Contrasting interactions in normal and tumor tissues we will then aim to identify factors, pathways or signals that would push that PCC, PGL and NB tumors towards benign state.
  • Swedish Research Council
    1 January 2020 - 31 December 2023
  • Swedish Cancer Society
    1 January 2020
    Neuroblastoma is the most common pediatric solid tumor and is characterized by a high degree of cellular heterogeneity. This heterogeneity may be an underlying cause of the different degrees of the disease as well as the variable response to treatment. Our preliminary data show that neuroblastoma is very heterogeneous in itself and resembles certain stages of neurallist differentiation into sympathetic neuroblast cells. Identification of the origin cell for these sympathetic tumors can be crucial in revealing the causes of disease heterogeneity and clinical behavior. Here we highlight the origin and heterogeneity of pediatric neuroblastomas. We will develop a new analytical and experimental approach based on single-cell transcriptomics to predict promising treatment strategies that take into account tumor heterogeneity. We will use human neuroblastoma tumors and mouse models to develop such a comparative differentiation assay, to make predictions, and finally to perform preliminary validations of strategies to induce tumors to differentiate. Heterogeneity in tumors including the presence of resistant clones represents a major challenge for the treatment of high-risk neuroblastoma (NB). There are currently no treatments that counteract the heterogeneity of the cancer. Classification of bulk tumors and corresponding predictions are too general. The understanding of heterogeneity will provide critical insight into the development of targeted therapeutic strategies. Knowing the pathways and target genes that can drive tumors to less metastatic and more mature conditions can be a key to cancer treatment.
  • Knut and Alice Wallenberg Foundation
    1 January 2018 - 1 January 2023
  • Mechanisms for tumor suppression mediated from chromosome 1p36
    Swedish Cancer Society
    1 January 2018
    Neuroblastoma arises from the same original cells that form parts of the nervous system. These cells are formed from the so-called "neural crest". Members of some families are at higher risk than others of developing neuralist tumors because they carry mutations in specific genes. We have recently discovered that genes that are mutated in some of these tumors play an essential role in whether neuralist cells live or die. If such genes are mutated in neuralist cells that should have died (by so-called "apoptosis") due to normal fetal development, they can escape their "death sentence". Later in life, the mutations can cause the formation of tumors We have shown that a gene named "EglN3" plays a crucial role in this process. Eg1N3 induces apoptosis in neural list cells and if Eg1N3 is inhibited, the effect is the opposite. We have also discovered that activation of Eg1N3 leads to apoptosis of neurblastoma cells and other cancer cells that originate from the neural list. The conclusion is that EglN3 plays a key role that determines whether neural list cells (and tumor cells derived from the neural list) survive or die. In our research, we try to understand the mechanism that is controlled by EglN3 because such knowledge can eventually have significance that helps us develop new therapies for patients with neuroblastoma. With the help of so-called "gene screening" we have also identified new genes that contribute to Eg1N3-induced apoptosis. One of these genes is called "KIF1Bb" and is localized to a region of chromosome 1 that is often eliminated in human neuroma tumor cells. During the last two decades, therefore, it has been suspected that chromosome 1 contains a neuroblastoma-inducing gene, but until now no one has been able to find it. Our preliminary data suggest that loss of KIF1Bb stimulates tumor growth. Increased understanding of how EglN3 together with KIF1Bb causes neuronal cell death will be of importance for attempts to develop new target proteins and therapies
  • Mechanisms for tumor suppression mediated from chromosome 1p36
    Swedish Cancer Society
    1 January 2014
    Neuroblastoma arises from the same original cells that form parts of the nervous system. These cells are formed from the so-called "neural crest". Members of some families are at higher risk than others of developing neuralist tumors because they carry mutations in specific genes. We have recently discovered that genes that are mutated in some of these tumors play an essential role in whether neuralist cells live or die. If such genes are mutated in neuralist cells that should have died (by so-called "apoptosis") due to normal fetal development, they can escape their "death sentence". Later in life, the mutations can cause the formation of tumors. We have shown that a gene named "EglN3" plays a crucial role in this process. Eg1N3 induces apoptosis in neural list cells and if Eg1N3 is inhibited, the effect is the opposite. We have also discovered that activation of Eg1N3 leads to apoptosis of neurblastoma cells and other cancer cells that originate from the neural list. The conclusion is that EglN3 plays a key role that determines whether neural list cells (and tumor cells derived from the neural list) survive or die. In our research, we try to understand the mechanism that is controlled by EglN3 because such knowledge can eventually have significance that helps us develop new therapies for patients with neuroblastoma. With the help of so-called "gene screening" we have also identified new genes that contribute to Eg1N3-induced apoptosis. One of these genes is called "KIF1Bb" and is localized to a region of chromosome 1 that is often eliminated in human neuroma tumor cells. During the last two decades, therefore, it has been suspected that chromosome 1 contains a neuroblastoma-inducing gene, but until now no one has been able to find it. Our preliminary data suggest that loss of KIF1Bb stimulates tumor growth. Increased understanding of how EglN3 together with KIF1Bb causes neuronal cell death will be of importance for attempts to develop new target proteins and therapies
  • Swedish Research Council
    1 January 2011 - 31 December 2013

Employments

  • Senior Lecturer, Molecular Tumour Biology, Department of Oncology-Pathology, Karolinska Institutet, 2023-

Degrees and Education

  • Docent, Karolinska Institutet, 2020

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