Anna Lindstrand

Anna Lindstrand

Adjunct Professor
Telephone: +46852482722
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
Part of:

About me

  • I am Professor and Consultant in Clinical Genetics in Stockholm, Sweden. Currently I am the head of the Clinical Genetics and Genomics diagnostic laboratory (Karolinska University Hospital) and group leader for Rare Diseases research group at the Department of Molecular Medicine and Surgery (Karolinska Institutet). My specific area of interest is the study of structural human genomic variation, its biological consequences and involvement in rare and common human disorders as well as cancer.

    My group members combine conventional and next generation genetic analysis with careful clinical assessments and functional follow up in primary cells and iPS cells. To characterize the breakpoints of chromosome rearrangements we use a variety of methodologies and next generation sequencing (NGS) platforms.

    This work is truly translational! Patients are initially identified in the health care system and outlined phenotypically and cytogenetically in the clinical genetic service. Then the research part takes over aiming to outline the exact genetic rearrangement down to single gene and breakpoint level in order to correlate symptoms with a specific gene defect. Finally, our findings are returned to the health care system in the form of new information about gene function.

    Academic honours, awards and prizes

    2015 Recipient of of the Jeanssons Foundation personal award to particularly outstanding young researchers

    2015-2017 Recipient of a three-year fellowship from Riksbankens Jubileumsfond

    2015-2018 Awarded four years of funding from Svenska Sällskapet för Medicinsk Forskning (SSMF:s stora anslag)

    2015-2017 Awarded 3 years of funding for clinical scientists from Marianne och Marcus Wallenbergs Stiftelse

    2016-2019 Selected for four year funding as Research Associate (forskarassistent), Karolinska Institutet

Research

  • Project 1: The role of structural genomic variation in human health and disease

    Backgound: Structural genomic variation comprises 1) copy-neutral balanced events (inversions and translocations) as well as 2) unbalanced events with either loss or gain of chromosome material (deletions, duplications, triplications and multi allelic copy number variants (CNVs). The size may vary from events that are visible in a light microscope (>5-10 Mb) down to the size of a single exon (<100-200 base pairs). In the past decade structural variants have emerged as important contributors to the genetic load of both rare and common disorders especially within the area of neurodevelopmental disease and malformation syndromes. However, a specific rearrangement often affects many genes and regulatory regions and the specific disease causing factors are still poorly characterized.

    Aim: These studies are focused on the detailed characterization of structural genomic rearrangements in order to identify the specific causative and modifying genes and to understand the underlying mutational mechanisms involved.

    Work Plan: We use short-, linked- and long-read whole genome sequencing (WGS) to characterize and identify structural variants. Patents with structural variants are recruited through the clinical genetic diagnostic laboratory where individuals with neurodevelopmental disorders and malformation syndromes are analyzed with chromosome analysis, oligonucleotide array-based comparative genomic hybridization (aCGH) and clinical WGS. After WGS and bioinformatics analysis functional follow up studies of candidate genes and variants are done in primary patient cells (e.g. fibroblasts, lymphocytes) and induced pluripotent stem cells.

    We have several ongoing studies:

    Study I) Identification and characterization of rare disease associated structural chromosomal variants by massive parallel whole genome sequencing

    The first objective is to implement WGS for the clinical diagnostic detection of structural variants. To this end, we develop novel bioinformatic analysis pipelines to identify both balanced and unbalanced structural variants from WGS data. The second objective is to study the rearrangement breakpoints and from the mutational signatures observed, infer the underlying mechanisms involved. Finally, we are interested in how the genes affected by structural variants cause disease. Our ambition is to characterize all genetic lesions in a given patient, from single base pair changes to large chromosomal rearrangements, and to follow up with functional studies. In this way, we will evaluate the relationship between structural variants and the burden of point mutations (an area that is still largely unexplored).

    Study II) Identification of new disease genes by sequencing balanced chromosomal aberrations.

    In this project we use WGS (described above) to study balanced chromosomal rearrangements (inversions and translocations). The hypothesis is that genes disrupted by the chromosomal breakpoints are driving the clinical symptoms seen in the rearrangement carriers. 


    Project 2: Computational development of bioinformatic tools and databases to interpret structural variants in individuals with rare diseases

    The aim of this project is to develop novel bioinformatic tools for the discovery and interpretation of disease-causing SV, as well as to evaluate the clinical feasibility of novel OMICs technologies. The project is translational and is carried out as a collaboration with Clinical genomics at Scilifelab Solna. The project will contribute to our knowledge on the structure and diversity of the human genome, as well as to bring novel technologies to the routine diagnostic workflow.


    Project 3: Cellular models to understand mechanisms underlying childhood neurodevelopmental disorders

    Here we use patient specific induced pluripotent stem cells (hiPSCs), which are translationally relevant to human in comparison with other models, in order to explore mechanisms of neurodevelopmental disorders and at the same time expand our knowledge about the normal functions and development of the healthy brain. Organoid 3D culture recapitulates development of various brain regions therefore is a unique tool to model brain disorders. Samples from patients’ diagnosed with rare neurodevelopmental disorders are obtained through clinical genetics (Karolinska University Hospital). This is a unique resource as they can help us understand more about how chromosomal rearrangement or loss of encoded proteins can affect neuronal development and function in vitro. Genes/disorders of particular interest are CTNND2, NFACS and Williams syndrome.

    Project 4: Resolving Structural Variant Complexity in Hematological Malignancies

     

    Here the primary goal is to elucidate the detailed mechanisms of structural variant formation and evolution in hematological malignancies. By integrating cutting-edge genomic sequencing and bioinformatics tools, we aim to map these variants more precisely and understand their exact structure and mechanisms of formation and role in cancer biology. This knowledge is crucial for developing targeted therapies that can more effectively treat these malignancies and improve patient outcomes.


    Previous and Current Research Funding:

    2025-2026 Cancerfonden

    2025-2027 Region Stockholm ALF

    2024 Hjärnfonden

    2024 Sällsyntafonden

    2023-2025 Region Stockholm HMT

    2022-2024 Region Stockholm ALF
    2020-2021 Region Stockholm - Högre klinisk forskare
    2018-2025 Swedish Research Council (Vetenskapsrådet)
    2019-2024 Cancerfonden

    2020 KI - StratNeuro
    2019-2023 Hjärnfonden
    2019 Läkaresällskapet
    2017-2022 Stockholms läns landsting, HMT
    2017-2021 Stockholms läns landsting, ALF
    2015-2018 Svenska Sällskapet för Medicinsk Forskning
    2015-2017 Marianne och Marcus Wallenbergs Stiftelse
    2015-2016 Science for Life Laboratory
    2015-2017 Riksbankens Jubileumsfond
    2015-2016 Jeanssons Foundation
    2014-2016 Hjärnfonden
    2015-2016 Kungl. Fysiografiska Sällskapet i Lund
    2013-2015 Swedish Research Council (Vetenskapsrådet)
    2016-2019 Karolinska Institutet
    2013-2015 Stockholms läns landsting, ALF
    2010-2013 Swedish Research Council (Vetenskapsrådet)


    Team members:
    Josephine Wincent, MD, PhD, Postdoc
    Jonas Carlsten, MD, PHD, Postdoc
    Mansoureh Shahsavani, PhD, Postdoc
    Maria Pettersson, PhD, Postdoc
    Jesper Eisfeldt, PhD, Postdoc
    Marlene Ek, PhD student

    Kristine Bilgrav Saether, PhD student

    Esmee ten Berk de Boer, PhD student


    Alumni:

    Jakob Schuy, PhD Postdoc
    Raquel Vaz, PhD, Senior researcher
    Wolfgang Hofmeister, PhD, Assistant professor

    Liselotte Vesterlund, PhD, Postdoc

    Ameli Norling, MD, PhD, Postdoc
    Vanja Börjesson, Master student
    Miriam Armenio, Research Assistant
    Alisa Foerster, Master student
    Amel Al-Murrani, Research Assistant

Articles

All other publications

Grants

  • Swedish Research Council
    1 January 2023 - 31 December 2026
    The project is focused on the detailed study of structural genomic variants (SVs). Such genetic mutations are in fact alterations in the DNA molecule structure and include copy number variants, inversions and translocations. A single event may affect many genes as well as regulatory regions and the specific phenotypic consequences will depend on the location, genetic content and type of SV.  Many times, the specific disease-causing mechanism is not known. Here, we plan to study the molecular genetic behavior of structural variants as well as the underlying mutational mechanisms involved.First, we will use genome sequencing to pinpoint the chromosomal breakpoints at the nucleotide level, characterize the genomic architecture at the breakpoints and study the relationship between structural variants and SNVs. Second, we will study how structural variants impact gene expression. Finally, we will functionally explore the disease mechanisms in vivo using zebrafish and in vitro using primary patient cells and induced pluripotent stem cells.Our studies will focus on the origin, structure and impact of structural variation on human disease. The results will directly lead to a higher mutation detection rate in genetic diagnostics. Through a better understanding of disease mechanisms our findings will also assist in the development of novel biomarkers and therapeutic strategies for patients with rare genetic disorders.
  • Swedish Cancer Society
    1 January 2022
    Acute myeloid leukemia (AML) annually affects more than 300,000 people worldwide, and in Sweden approximately 350 new cases are diagnosed each year. The prognosis is poor, many relapse several times in the disease and about 75% die within five years. The treatment is based on combining several different cytostatics, with cytarabine (ara-C) being the most effective. Many different genetic changes have been described in AML and some of these are used clinically as prognostic markers and to find relapses early. However, there are no genetic tests that can be used to tailor cancer treatment. Recently, it has been shown that SAMHD1 expression influences treatment effect in AML patients. Lower expression leads to better effect of ara-C. We have established a zebrafish model that will be used to (i) study in vivo how SAMHD1 affects ara-C effect, (ii) identify chemicals that lower SAMHD1 expression and function, and (iii) identify potential drugs that are not affected by SAMHD1. We plan here to study in a zebrafish model of AML how genetic factors affect the effect of chemotherapy and to use the same system to identify chemicals that have a similar effect. This is very relevant to the leukemia field, and can be used in different types of leukemia. An advantage of developing such an animal model is to be able to research specific mutations found in patients and how they affect the treatment in a rapid manner. Therefore, we can offer patients the best treatment and improve their survival.
  • Swedish Research Council
    1 January 2020 - 31 December 2025
    The project is focused on the detailed study of structural genomic variants (SVs). Such genetic mutations are in fact alterations in the DNA molecule structure and include copy number variants, inversions and translocations. A single event may affect many genes as well as regulatory regions and the specific phenotypic consequences will depend on the location, genetic content and type of SV.  Many times, the specific disease-causing mechanism is not known. Here, we plan to study the molecular genetic behavior of structural variants as well as the underlying mutational mechanisms involved.First, we will use genome sequencing to pinpoint the chromosomal breakpoints at the nucleotide level, characterize the genomic architecture at the breakpoints and study the relationship between structural variants and SNVs. Second, we will study how structural variants impact gene expression. Finally, we will functionally explore the disease mechanisms in vivo using zebrafish and in vitro using primary patient cells and induced pluripotent stem cells.Our studies will focus on the origin, structure and impact of structural variation on human disease. The results will directly lead to a higher mutation detection rate in genetic diagnostics. Through a better understanding of disease mechanisms our findings will also assist in the development of novel biomarkers and therapeutic strategies for patients with rare genetic disorders.
  • Swedish Research Council
    1 January 2019 - 31 December 2021
  • Swedish Research Council
    1 January 2019 - 31 December 2021
  • Zebrafish studies to develop new treatments for drug-resistant leukemia
    Swedish Cancer Society
    1 January 2018
    Acute myeloid leukemia (AML) annually affects more than 300,000 people in the world and in Sweden about 350 new cases are diagnosed each year. The prognosis is poor, many relapse several times in disease and about 75% die within five years. The treatment is based on combining several different chemotherapy drugs where cytarabine (ara-C) is most effective. Many different genetic changes are described at AML and some of these are used clinically as prognostic markers and to find relapses early. However, there are no genetic tests that can be used to tailor cancer treatment. Recently, it has been shown that AML patients with genetic variants in the SAMHD1 gene have a better effect of ara-C. We have established a zebrafish model that will be used to (i) study in vivo how SAMHD1 affects the ara-C effect, (ii) identify chemicals that function in the same way as SAMHD1 and (iii) study if / how SAMHD1 affects cancer development. The goal is to use the zebrafish model to identify chemicals that increase the cells' sensitivity to cytostatics. In the long term, the results can lead to new treatment strategies and better survival for people with AML. This is very relevant to the entire leukemia area. One prerequisite for being able to offer individual-based care and treatment to patients with leukemia is that we first understand how congenital variants affect cancer development and treatment effect.
  • Swedish Research Council
    1 January 2018 - 31 December 2021
  • Swedish Research Council
    1 January 2013 - 31 December 2015
  • Swedish Research Council
    1 September 2012 - 31 August 2013

Employments

  • Consultant, Clinical genetics and genomics, Karolinska University Hospital, 2019-
  • Director Clinical Genetics Laboratory, Clinical Genetics and Genomics, Karolinska University Hospital, 2018-
  • Adjunct Professor, Department of Molecular Medicine and Surgery, Karolinska Institutet, 2020-2028
  • Specialist physician, Clinical Genetics and Genomics, Karolinska University Hospital, 2012-2019
  • Resident, Clinical genetics and Genomics, Karolinska University Hospital, 2002-2012

Degrees and Education

  • Docent, Karolinska Institutet, 2016
  • Degree Of Doctor Of Philosophy, Department of Molecular Medicine and Surgery, Karolinska Institutet, 2010
  • University Medical Degree, Karolinska Institutet, 1999

Visiting research fellowships

  • Visiting professor, Pacific Northwest Diabetes Research Institute, 1 month visiting professor, 2024-2024
  • Postdoctoral Researcher, Duke University, 2 year VR funder postdoc, focus on ciliopathies, CNV screening and zebrafish modelling, 2010-2012

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