Susanne Schlisio

Susanne Schlisio

Senior Lecturer | Docent
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 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.

    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

Research

  • *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
    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

Teaching

Articles

All other publications

Grants

  • 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
  • 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, Department of Oncology-Pathology, Karolinska Institutet, 2023-

Degrees and Education

  • Docent, Karolinska Institutet, 2020

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