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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 (̽����ѡ). 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), ̽����ѡ

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

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 ̽����ѡ
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