Ann Nordgren

Ann Nordgren

Adjunct Professor
Visiting address: Karolinska Institutet, BioClinicum J10:20, Visionsgatan 4, 17164 Solna
Postal address: K1 Molekylär medicin och kirurgi, K1 MMK Sällsynta diagnoser, 171 76 Stockholm
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About me

  • Ann Nordgren is Professor and Senior Physician of Clinical Genetics. She received her medical degree in 1991, licence to practice medicine 1993 and PhD degree 2001 at Karolinska Institute, Sweden, and became board certified  specialist in Clinical Genetics in 2002. She became Adjunct Professor in Clinical genetics at Karolinska Institutet 2015 and Professor of Clinical Genetics in 2022 at the Department of Biomedicine, Gothenburg University. She has previously been the head of the Clinical Genetics Department at Norrlands Universitetssjukhus 2002-2004, head of Clinical Genetics  outpatient clinic 2004-2012, Vice Head of the Department of Clinical genetics 2012-2018, and Project leader of the Center for Rare Diseases at Karolinska University Hospital 2012-2018. Ann Nordgren is, together with Anna Lindstrand group leader for the research group Rare Diseases at Karolinska since 2015. Her clinical work is mainly focused on syndrome and leukemia diagnostics, using detailed phenotyping and modern omics technologies.  In 2012 Ann Nordgren started a clinical and research multidisciplinary expert team for syndrome diagnostics and this team is now part of the iUndiagnosed Diseases Network International (UDNI) Undiagnosed Diseases Program (UDP). Ann Nordgren is the Swedish coordinator of the European Reference Network (ERN) for Congenital malformations and Intellectual Disability (ERN ITHACA) and co-chair of the UDNI diagnostic working group.

    Ann Nordgren initiated and has led the National Genomic Medicine Sweden Childhood Cancer Predisposition project since 2021 that has resulted in changed clinical routines in 2024 where germline genome sequencing was introduced in clinical practice for all children with cancer in Sweden.  She is also initiator and coordinator of the GMS Undiagnosed Diseases Network (UDN Sweden) project, where children with intellectual disabilities and congenital malformation syndromes without an etiological diagnosis are offered multi-omics technologies combined with careful phenotyping.

Research

  • Ann Nordgren studies Rare Diseases from a holistic perspective through several different approaches, a. Multiomics, b. Register-based studies,   c. Careful phenotyping of diagnosed rare diseases and d. Psychosocial studies. e. Collaboration with patients and families.

    Ann Nordgren has supervised 20 PhD students as well as seven postdocs, and her research has resulted in more than 195 peer-reviewed papers.

    Ann Nordgren is PI for the following projects:

    ChiCaP: The Childhood Cancer Predisposition, ChiCaP project: This project aims to investigate congenital genetic causes of cancer in

    children by analyzing both normal and cancer cells using modern omics-based methods. The goal is to identify new syndromes with hereditary predisposition to childhood cancer, discover new therapeutic targets, and generate knowledge that can lead to improved diagnostics, treatment, follow-up, and prevention. By increasing our understanding of the underlying mechanisms of childhood leukemia, we strive to reduce mortality, morbidity, and long-term complications in affected children. Specific objectives: To identify novel ChiCaP syndromes using modern omics technologies; To map breakpoints in somatic structural chromosomal aberrations and look for disease mechanisms and treatment targets and to search for these aberrations in neonatal screening samples (PKU samples) and To evaluate whether broader genetic testing with long-read whole genome sequencing (WGS), RNA sequencing, and deep exome sequencing can replace current in silico gene panel analyses of WGS data, with the aim of improving diagnostic accuracy for ChiCaP syndromes.

    GMS UDN Sweden: GMS Undiagnosed Diseases Network Sweden. The study provides diagnostic support to children with unexplained intellectual disabilities and congenital malformations using multi-omics approaches. We perform longread and shortread DNA and RNA sequencing, deep exome sequencing and Episignature analyses to find diagnoses in individuals with rare ID syndromes and congenilal malformation syndromes. All findings are returned to the patient and the referring physicians.

    UNIKA: This project aims to conduct a comprehensive phenotypic characterization of individuals with known genetic etiologies of rare syndromes, emphasizing behavior, brain abnormalities, and biological markers. By investigating individuals with established genetic diagnoses, we seek to understand how specific genetic variants influence brain development, behavior, and overall functioning. The project utilizes clinical assessments, advanced eye-tracking technology, experimental psychological methods, cognitive profiling, and state-of-the-art imaging techniques, including functional and structural MRI, to explore key neurodevelopmental aspects. Blood biomarkers are also analyzed to identify potential links between hormonal or metabolic imbalances and behavioral patterns. Functional studies in induced pluripotent stem cells (iPSC) are being conducted, with a current focus on Williams syndrome. This integrative approach aims to identify syndrome-specific phenotypes and underlying mechanisms contributing to intellectual and neuropsychiatric challenges in rare diseases. In addition, we are developing  games for cognitive and motor skill testing.

    PSYCHOSOCIAL STUDIES: Alongside our biomedical research, we also investigate the social, cultural, and emotional dimensions of living with a rare disease or undergoing the diagnostic process. Using both qualitative and quantitative methods—including questionnaires, in-depth interviews, and focus groups—we work closely with patients, families, and healthcare providers. These studies explore experiences of primary and specialist care, perceptions of genetic testing, and how individuals interpret and respond to genetic information. We also examine how cultural and societal factors shape these experiences. The insights gained help improve communication, support services, and clinical practices, ensuring they are more responsive to the needs and realities of those affected.

    RAreDIseases and CAncer (RADICA): Ann Nordgren is register owner of a large population-based register where genetic data from Region Stockholm has been linked to ICD codes to study comorbidities and cancer risk in rare diseases and how the rare disease affect the families.

    SYMPTOMICS: The project aims to develop a scalable and sustainable infrastructure for managing health data related to rare diseases (RDs). At its core is the creation of a regional, structured data layer-a Healthcare Data Warehouse based in Region Stockholm at Karolinska University Hospital. The data-layer, named SYMPTOMICS will be designed to support diagnostics, phenotype–genotype integration and clinical decision-making. The data-layer will serve as a regional hub for the storage, analysis, and secure sharing of diverse health data. The data includes structured phenotypic information, clinical laboratory results, multi-omics data, observational health data (including electronic health records from multiple healthcare providers), patient-reported outcomes, and published Real-World Evidence. It will enable automated entry of health data into National health and quality registers. SYMPTOMICS will be designed with global applicability in mind - including semantics, regulations, data logistics, and user needs.

Teaching

  • She has served as the responsible subject representative for Clinical Genetics and has, since 2022, been actively involved in the implementation of the new medical program in Gothenburg.

Selected publications

Articles

All other publications

Grants

  • Barncancerfonden
    1 January 2024 - 31 December 2024
  • Barncancerfonden
    1 January 2024 - 31 December 2024
  • Swedish Research Council
    1 January 2024 - 31 December 2026
    Pediatric Acute Lymphoblastic Leukemia (ALL) arises from lymphocyte progenitors and is known to present a hierarchy of cell differentiation, making it a suitable model disease for studying differentiation state instability and cancer stem cells. We will analyze ALL samples during treatment and at relapsed from the same patient using a novel method that allows RNA sequencing and genomic sequencing in jointly in the same single cells. Using this method, we will characterize the clonal structure of the leukemia and analyze clonal leukemic cell types in the primary sample of patients which later relapse. Since we obtain data on both the genotype (genomic sequencing) and gene expression profile (RNA-seq) of each cell, we can trace clonal expansions that are mainly driven by epigenetic factors as well as those driven by genetic alterations. Based on this map of treatment escape, we will 1) Determine molecular targets for therapy using a gene editing screen and 2) Test the added value of single-cell genomics for diagnostic tests (in collaboration with clinical genetics). The ultimate goal of the project is to gain a deep understanding of the cancer stem cell population in pediatric ALL tumors in a way that will have a direct impact on the treatment and prevention of ALL recurrence. To ensure that potential discoveries will have clinical diagnostic adaptation, we have partnered with experienced clinicians in genetics and hematopathology.
  • Swedish Cancer Society
    1 January 2023
    Research has in recent years shown that between 10-15% of all children with cancer have a congenital genetic change. This applies above all to children with adult tumors, various forms of cancer, close relatives affected by childhood cancer, children who have reacted with severe side effects of cancer treatment and children with malformations, overgrowth syndrome or other rare diseases. Congenital genetic changes can negatively affect prognosis by affecting treatment response and increasing the risk of therapy-related severe side effects. Such complications may in turn be possible to avoid if the congenital diagnosis is detected in time. All different forms of childhood cancer are studied using genetic analyzes with whole genome sequencing and epidemiological studies where we also use AI and machine learning. The project is about improving genetic diagnostics and introducing whole genome sequencing regarding congenital genetic changes in clinical routine. The project affects both diagnostics, treatment and prevention and will lead to more children being offered precision medicine with targeted treatments and that treatment complications can be avoided and new treatment targets can be identified. In addition, preventive screening programs can be offered to relatives at risk of cancer. We want to understand why children get cancer and understand the mechanisms of its occurrence and find ways to improve survival and quality of life for survivors of childhood cancer and their relatives. We want to try to answer the following questions. Is the incidence of childhood cancer higher in specific genetic syndromes? Is cancer more common in families with a child with cancer and how big is the risk for relatives? Are congenital genetic abnormalities detected in cancer cells at diagnosis correlated to prognosis, treatment outcome, infectious diseases, seasons and geographic locations? Can we find new disease and cancer associations?
  • Barncancerfonden
    1 January 2022 - 31 December 2022
  • Molecular and Epidemiological studies of Childhood Cancer predisposition
    Cancerföreningen i Stockholm
    1 January 2022 - 31 December 2024
  • Swedish Research Council
    1 December 2021 - 31 December 2025
    Our overall ambition is to study childhood cancer etiology through genetic, epidemiological and machine learning studies based on a novel machine learning algorithm in order to discover novel genes, pathways and molecular mechanisms as well as environmental factors critical in the development of childhood cancer. Our aim is to discover novel targets for therapy and situations where treatment should be modified to avoid toxicity or therapy resistance and when genetic counselling should be offered the family. We also want to identify risk factors for cancer development and contribute to the development of surveillance protocols, increase awareness of genetic predisposition and investigate the benefits of integrating germline sequencing into clinical practice in pediatric oncology. The long-term objective is to identify risk factors and to translate rare phenotypes into gene discoveries and to improve diagnostics and precision medicine in order to reduce morbidity and mortality of cancer in children.
  • Swedish Research Council
    1 January 2021 - 31 December 2023
  • Swedish Cancer Society
    1 January 2020
    In recent years, research has shown that more than 10% of all children affected by cancer have congenital genetic changes as a contributing cause of their disease. This is especially true for children with rare tumors that normally only occur in adults, children who suffer from several different cancers, children with several close relatives who suffered from cancer at an early age, children who suffer from abnormally severe side effects of cancer treatment and children with cancer and malformations, overgrowth syndrome, epilepsy, intellectual disability, autism, or other rare disease. It is important to find these patients as it can save lives. We want to introduce diagnostics into clinical routine to look for known and new congenital genetic abnormalities and then compare them with genetic abnormalities in cancer cells in people with cancer, children whose cancer type or side effect profile gives strong suspicion of congenital genetic causes and people who included in families where more than one child has been affected by cancer. We want to use new DNA and RNA based methods that are based on sequencing of the entire human genome. In cases where we find new suspected cancer-associated genes, we will proceed with various functional studies in animal models and cells from patients. I want to identify patients who need a tailored treatment and understand the mechanisms of emergence and find new disease genes behind the syndrome and cancer. Increased knowledge about familial cancer and why certain syndromes are associated with cancer risk and increased sensitivity to cytotoxic drugs and radiation is important and will lead to improved care, tailored therapies and opportunities to implement preventive measures in the affected individual and his family. . The research also leads to increased knowledge about childhood cancer in general, which can lead to improved diagnostics and treatment and improved survival.
  • Constitutional genetic aberrations behind childhood cancer predisposition
    Swedish Cancer Society
    1 January 2019
    In recent years, research has shown that more than 10% of all children affected by cancer have congenital genetic changes as a contributing cause of their disease. This is especially true for children with rare tumors that normally only occur in adults, children who suffer from several different cancers, children with several close relatives who suffered from cancer at an early age, children who suffer from abnormally severe side effects of cancer treatment and children with cancer and malformations, overgrowth syndrome, epilepsy, intellectual disability, autism, or other rare disease. It is important to find these patients as it can save lives. We want to introduce diagnostics into clinical routine to look for known and new congenital genetic abnormalities and then compare them with genetic abnormalities in cancer cells in people with cancer, children whose cancer type or side effect profile gives strong suspicion of congenital genetic causes and people who included in families where more than one child has been affected by cancer. We want to use new DNA and RNA based methods that are based on sequencing of the entire human genome. In cases where we find new suspected cancer-associated genes, we will proceed with various functional studies in animal models and cells from patients. I want to identify patients who need a tailored treatment and understand the mechanisms of emergence and find new disease genes behind the syndrome and cancer. Increased knowledge about familial cancer and why certain syndromes are associated with cancer risk and increased sensitivity to cytotoxic drugs and radiation is important and will lead to improved care, tailored therapies and opportunities to implement preventive measures in the affected individual and his family. . The research also leads to increased knowledge about childhood cancer in general, which can lead to improved diagnostics and treatment and improved survival.
  • Barncancerfonden
    1 January 2019 - 31 December 2019
  • Swedish Research Council
    1 January 2019 - 31 December 2021
  • Swedish Research Council
    1 January 2019 - 31 December 2021
  • The importance of innate genetic factors for childhood cancer
    Swedish Cancer Society
    1 January 2018
    Little is known about the importance of congenital changes in childhood cancer. Previously, it has been said that congenital syndrome and cancer are two completely different things. In recent years, research has shown that there are often the same genes and signal pathways that are involved in the different conditions. Most cases occur sporadically and it is very rare for several children within the same family to suffer. However, there are rare families where several close relatives suffered from childhood cancer. These families are very interesting from a research point of view because they allow the identification of cancer-associated genes. There are also congenital syndromes that increase the risk of cancer. The purpose is to understand emergence mechanisms and find new disease genes behind syndrome and childhood cancer. We want to use modern technology with sequencing of all human genes to characterize innate genetic abnormalities and compare with genetic abnormalities in cancer cells in people with syndrome and in families where more than one child affected by childhood cancer. We have also collected 380,000 people with various rare genetic diagnoses in a unique registry study to investigate cancer incidence and risk in specific rare diagnoses. Identification of new disease genes and mechanisms behind syndrome and cancer development and familial cancer will give increased knowledge of childhood cancer as a whole and that this can eventually lead to opportunities for preventive measures and new therapies. If cancer cells can be detected already in PKU samples, this can lead to a new understanding of the growth of cancer cells. The registry study is the first of its kind and will lead to new insights on cancer risk in relatives and other associated symptoms in various congenital rare diseases and childhood cancer.
  • Swedish Research Council
    1 January 2018 - 31 December 2020
  • The importance of innate genetic factors for childhood cancer
    Swedish Cancer Society
    1 January 2017
    Little is known about the importance of congenital changes in childhood cancer. Previously, it has been said that congenital syndrome and cancer are two completely different things. In recent years, research has shown that there are often the same genes and signal pathways that are involved in the different conditions. Most cases occur sporadically and it is very rare for several children within the same family to suffer. However, there are rare families where several close relatives suffered from childhood cancer. These families are very interesting from a research point of view because they allow the identification of cancer-associated genes. There are also congenital syndromes that increase the risk of cancer. The purpose is to understand emergence mechanisms and find new disease genes behind syndrome and childhood cancer. We want to use modern technology with sequencing of all human genes to characterize innate genetic abnormalities and compare with genetic abnormalities in cancer cells in people with syndrome and in families where more than one child affected by childhood cancer. We have also collected 380,000 people with various rare genetic diagnoses in a unique registry study to investigate cancer incidence and risk in specific rare diagnoses. Identification of new disease genes and mechanisms behind syndrome and cancer development and familial cancer will give increased knowledge of childhood cancer as a whole and that this can eventually lead to opportunities for preventive measures and new therapies. If cancer cells can be detected already in PKU samples, this can lead to a new understanding of the growth of cancer cells. The registry study is the first of its kind and will lead to new insights on cancer risk in relatives and other associated symptoms in various congenital rare diseases and childhood cancer.
  • The importance of innate genetic factors for childhood cancer
    Swedish Cancer Society
    1 January 2016
    Little is known about the importance of congenital changes in childhood cancer. Previously, it has been said that congenital syndrome and cancer are two completely different things. In recent years, research has shown that there are often the same genes and signal pathways that are involved in the different conditions. Most cases occur sporadically and it is very rare for several children within the same family to suffer. However, there are rare families where several close relatives suffered from childhood cancer. These families are very interesting from a research point of view because they allow the identification of cancer-associated genes. There are also congenital syndromes that increase the risk of cancer. The purpose is to understand emergence mechanisms and find new disease genes behind syndrome and childhood cancer. We want to use modern technology with sequencing of all human genes to characterize innate genetic abnormalities and compare with genetic abnormalities in cancer cells in people with syndrome and in families where more than one child affected by childhood cancer. We have also collected 380,000 people with various rare genetic diagnoses in a unique registry study to investigate cancer incidence and risk in specific rare diagnoses. Identification of new disease genes and mechanisms behind syndrome and cancer development and familial cancer will give increased knowledge of childhood cancer as a whole and that this can eventually lead to opportunities for preventive measures and new therapies. If cancer cells can be detected already in PKU samples, this can lead to a new understanding of the growth of cancer cells. The registry study is the first of its kind and will lead to new insights on cancer risk in relatives and other associated symptoms in various congenital rare diseases and childhood cancer.
  • Swedish Research Council
    1 January 2016 - 31 December 2018
  • Swedish Research Council
    1 January 2012 - 31 December 2014

Employments

  • Adjunct Professor, Department of Molecular Medicine and Surgery, Karolinska Institutet, 2019-2027

Degrees and Education

  • Docent, Karolinska Institutet, 2010
  • Doctor Of Philosophy, Department of Molecular Medicine and Surgery, Karolinska Institutet, 2001

Supervision

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