Johan Björkegren

Johan Björkegren

Principal Researcher | Docent
Telephone: +46852482911
Visiting address: Novum, Blickagången 6, 14157 Huddinge/Stockholm
Postal address: H7 Medicin, Huddinge, H7 Metabolism/ICMC Björkegren, 171 77 Stockholm

About me

  • Focusing on cardiovascular diseases, the goal of my research is to use
    multi-modal big data analysis to create reliable network models of human
    biology and disease.
    * PROFESSOR | Genetics and Genomic Sciences
    * PROFESSOR | Medicine, Cardiology
    Department of Genetics and Genomic Sciences, Icahn Institute for Genomics
    and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York,
    2003- Associate Professor of Molecular Medicine, Karolinska Institutet,
    Stockholm, Sweden
    2015- Visiting Professor, University of Tartu, Tartu, Estonia
    Focusing on cardiovascular diseases, the goal of my research is to use
    multi-modal big data analysis to create reliable network models of human
    biology and disease. Network models have enormous potential to improve our
    ability to predict disease risk, identify new therapeutic targets, and to
    monitor molecular effects of treatments. To achieve this goal, I have
    designed and generated a range of clinical datasets of cardiovascular disease
    that combine detailed clinical characteristics with imaging, genomics,
    proteomics, and other types of data.
    My research has long focused on cardiovascular disease. My early work
    explored the role of triglyceride-rich lipoproteins in coronary artery
    disease (CAD), and my postdoctoral studies in mouse models established the
    hepatic gene microsomal triglyceride transfer protein as a key target to
    lower plasma cholesterol levels and reduce atherosclerosis. Since then, my
    primary focus has been systems analyses to generate network models from large
    genomic datasets—both from CAD patients in the clinic and from cellular and
    mouse models of atherosclerosis progression and regression in the laboratory.
    Throughout the last decade, I have designed and led a range of clinical and
    mouse model studies to elucidate the inherit complexity of CAD. As one of the
    first clinical scientists to apply the emerging technologies of molecular
    profiling to large patient cohorts, I have revealed the role of functionally
    associated genes in several molecular networks that drive CAD. A common
    complex disease such as CAD cannot be understood nor cured by targeting
    isolated genes. Rather, the focus needs to be on molecular disease processes
    mirrored by regulatory-gene networks that capture the combined effects of
    many genetic and environmental risk factors.
    To this end, at Karolinska Institutet and Tartu University Hospital, much of
    my time has gone into gathering a truly unique biobank from CAD patients
    undergoing different forms of heart surgery. The Stockholm-Tartu
    Atherosclerosis Reverse Network Engineering Task (STARNET) is a joint study
    initiative between the cardiovascular chief surgeon at the Tartu University
    Hospital in Estonia, Dr. Arno Ruusalepp, and myself. Using the STARNET
    bio-bank, I have since 2013 been mainly active at the Department of Genetics
    and Genomic Sciences at Mount Sinai where we have generated RNA sequence data
    from up to nine CAD-relevant tissues isolated from over 800 hundred
    clinically well–characterized patients. This unprecedented dataset is the
    main resource for our current efforts to generate network models that predict
    the risk for and clinical outcomes of CAD.
    My entrepreneurial ambitions have focused on translating the results of our
    systems genetic research into new therapies and diagnostics for patients at
    risk for or suffering CAD. I have launched several entrepreneurial projects.
    Of particular importance is Clinical Gene Networks AB—the first Bio-IT
    company in Sweden, founded in 2003 with the goal of exploring “clinical”
    networks to generate the next generation of diagnostics and therapies based
    on network models of complex diseases. Since 2019, I am reestablishing myself
    at the Karolinska Institutet at the Department of Medicine at Huddinge
    University Hospital.
    2016 - NIH-director Francis Collins, blog on Science 2016 article [1]*
    2010-2013 - Senior investigator position, Swedish Heart-Lung foundation
    2008-2009 - Senior investigator award, Karolinska Institutet
    2008 - Invited speaker to the Rudbeck Seminar series, Uppsala University,
    2004-2007 - Research Assistant position for the Swedish research
    2003 - Finalist in the Young Investigator Award, International Society of
    Atherosclerosis, Kyoto
    1999-2002 - Fogarty fellowship (VR), University of San Francisco, University
    of California
    /Stockholm Business School, SU, Sweden/
    /Karolinska Institutet, Stockholm, Sweden/
    /Medical School/
    Karolinska University Hospital, Stockholm
    Fully qualified physician
    /Karolinska Institutet, Sweden/
    /Gladstone Institute of Cardiovascular Disease, University of California, San
    Francisco, CA, USA/
    CAD mouse models


  • I use multi-modal big data analysis to create new and reliable network models
    of human molecular biology in health and disease that can lead to better
    disease prediction, monitoring and therapies. To this effort I have created
    clinical datasets of mainly cardiovascular disease patients in Sweden,
    Estonia and now in the US that are enriched for many of these data modalities
    including genetics, -omics (epigenetics, RNA, proteins, metabolites and
    lipids) combined with detailed clinical characteristics including imaging.
    I have a broad background in the design and analysis of clinical studies
    apprehending and applying the new screening and bioinformatics analysis tools
    to elucidate the true complexity of common diseases. The focus of these
    studies has been the role of functionally associated genes in molecular
    networks driving disease. Vital to this approach of a more granular
    understanding of complex disease biology is to originate these studies in
    humans suffering the disease whereas animal and cell disease model systems
    have chiefly been used for the purpose of validating key disease drivers and
    processes first identified in humans (i.e. top-down vs. a bottom-up
    *STARNET bio-bank*
    This effort has now resulted in one of the world’s most unique
    cardiometabolic disease (CMD)-related dataset, STARNET, published in /Science
    and Nature /journals/. /Currently, we are expanding STARNET (v2) (with 1316
    coronary artery disease (CAD)-affected subjects and 372 subjects verified to
    be CAD-free (nonCAD)) now processing samples allowing transomic analyses
    (epigenomics, transcriptomics and proteomics) including single nuclei RNAseq
    and with the additions of portal vein and the gut microbiome.* *Moving
    forward, I am highly driven, motivated and focused to expand the central
    theme of my research strategies
  • /a global understanding of the molecular
    regulatory-gene landscape enabling diagnostics and therapies of
    molecularly-defined subcategories of CMD patients (i.e. precision medicine)/.
    *Complete List of Published Work in MyBibliography:*
    1) Franzén et al. *“*Cardiometabolic Risk Loci Share Downstream /Cis/ and
    /Trans/ Genes Across Tissues and Diseases” /Science /19 Aug 2016:Vol.
    353, Issue 6301, pp. 827-830.
    2) Zeng et al.. “Contribution of Gene Regulatory Networks to Heritability
    of Coronary Artery Disease”./ J Am Coll Cardiol. /2019 Jun
  • 73(23):2946-2957. doi: 10.1016/j.jacc.2019.03.520.
    3) *Cohain el al. “*/An integrative multiomic network model links lipid
    metabolism to glucose regulation in coronary artery disease/” Nat
    Commun. 2021 Jan 22
  • 12(1):547.
    4) *Hartman et al. “*/Sex-stratified gene regulatory networks reveal
    differentially activated key drivers of human coronary artery disease”/
    Circulation. 2021 Feb 16
  • 143(7):713-726.
    5) Koplev et al. “/A mechanistic framework for cardiometabolic and
    coronary artery diseases/” Nature Cardiovascular Research, in press
    (available online January 12th, 2022)
    *Historical contributions to Science:*
    *1. *In my PhD work I studied the role of apolipoprotein (apo) and lipid
    composition of triglyceride-rich lipoproteins (TRLs) for CAD. I found that
    the TRL content of apoCI was particularly relevant for risk of developing
    early CAD. This work involved both sampling and characterization of patients
    and a wide range of molecular laboratory methods.
    1) 1) Bjorkegren, J. (2006). "Dual roles of apolipoprotein CI in the
    formation of atherogenic remnants." /Curr Atheroscler Rep/ 8(1): 1-2.
    2) Hamsten, A., A. Silveira, S. Boquist, R. Tang, M. G. Bond, U. de
    Faire and J. Bjorkegren (2005). "The apolipoprotein CI content of
    triglyceride-rich lipoproteins independently predicts early
    atherosclerosis in healthy middle-aged men." J Am Coll Cardiol 45(7):
    3) Bjorkegren, J., S. Boquist, A. Samnegard, P. Lundman, P. Tornvall, C.
    G. Ericsson and A. Hamsten (2000). "Accumulation of apolipoprotein
    C-I-rich and cholesterol-rich VLDL remnants during exaggerated
    postprandial triglyceridemia in normolipidemic patients with coronary
    artery disease." /Circulation/ 101(3):227-230.
    4) Bjorkegren, J., F. Karpe, R. W. Milne and A. Hamsten (1998).
    "Differences in apolipoprotein and lipid composition between human
    chylomicron remnants and very low-density lipoproteins isolated from
    fasting and postprandial plasma." /J Lipid Res/ 39(7): 1412-1420.
    2) During my post-doc years at UCSF, CA, I generated genetically modified
    mouse models relevant for CAD and atherosclerosis. I carefully
    investigated the hepatic gene microsomal triglyceride transfer protein
    (/Mttp/) conditional gene knockout in the liver and heart examining the
    effects of /Mttp /deletion on plasma cholesterol levels, liver steatosis
    and fat accumulation and secretion of lipoproteins from the heart.
    1) Larsson, S. L., J. Skogsberg and J. Bjorkegren (2004). "The
    low-density lipoprotein receptor prevents secretion of dense
    apoB100-containing lipoproteins from the liver." /J Biol Chem
    /279(2): 831-836.
    2) Bjorkegren, J., A. Beigneux, M. O. Bergo, J. J. Maher and S. G. Young
    (2002). "Blocking the secretion of hepatic very low-density
    lipoproteins renders the liver more susceptible to toxin-induced
    injury." /J Biol Chem/ 277(7): 5476-5483.
    3) Bjorkegren et al. (2001). "Lipoprotein secretion and triglyceride
    stores in the heart." /J Biol Chem/ 276(42): 38511-38517
    4) Raabe et al. (1999). "Analysis of the role of microsomal triglyceride
    transfer protein in the liver of tissue-specific knockout mice." /J
    Clin Invest/ 103(9): 1287-1298.
    3) I have extensively used these mouse models also after my post-doc for
    key CAD target validation and in combination with holistic functional
    transcriptomic studies of gene expression during atherosclerosis
    progression and regression. From these studies, I have defined regulatory
    gene networks driving atherosclerosis progression and regression that are
    highly relevant for my current studies of patients of CAD to establish
    networks active both in early and late phases of coronary
    1) Bjorkegren, J. et al. (2014). "Plasma cholesterol-induced lesion
    networks activated before regression of early, mature, and advanced
    atherosclerosis." /PLoS Genet./ 10(2): e1004201.
    2) Shang et al. (2014). "Lim domain binding 2: a key driver of
    transendothelial migration of leukocytes and atherosclerosis."
    /Arterioscler Thromb Vasc Biol/ 34(9): 2068-2077.
    3) Skogsberg et al. (2008). "Transcriptional profiling uncovers a
    network of cholesterol-responsive atherosclerosis target genes."
    /PLoS. Genet./ 4(3): e1000036.
    4) Kovacs et al. (2007). "Human C-reactive protein slows atherosclerosis
    development in a mouse model with human-like hypercholesterolemia."
    /Proc. Natl. Acad. Sci./ U S A 104(34): 13768-13773.
    4) I have uniquely designed clinical studies to sample multiple vascular and
    metabolic tissues enabling systems genetics approaches to study CAD by
    generating genomics datasets from the STAGE and STARNET cohorts. For
    these types of functional genomics studies, I have evolved as a leader in
    the field of network CAD biology.
    1) Foroughi et al. (2015). "Expression quantitative trait Loci acting
    across multiple tissues are enriched in inherited risk for coronary
    artery disease." /Circ Cardiovasc Genet/ 8(2): 305-315.
    2) Schadt, E. E. and J. L. Bjorkegren (2012). "NEW: network-enabled
    wisdom in biology, medicine, and health care." /Science Transl. Med/.
    4(115): 115rv111
    3) Hägg et al. (2009). "Multi-organ expression profiling uncovers a
    gene module in coronary artery disease involving transendothelial
    migration of leukocytes and LIM domain binding 2: the Stockholm
    Atherosclerosis Gene Expression (STAGE) study." /PLoS genetics/ 5:
    4) Tegner, J. and J. Bjorkegren (2007). "Perturbations to uncover gene
    networks." /Trends Genet/ 23(1): 34-41.
    5) Founder of one of Sweden’s leading biotech companies in the Bio-IT
    sectors (Clinical Gene Networks AB). [2]* *


    *Lecturer in the PhD program*, “Systems biology- from model organism to
    complex diseases” (# 2085) at the School of Medical Bioinformatics (FMB),
    Strategy and Development Office, Karolinska Institutet: Cardiovascular
    systems medicine”, 2 scheduled hours per semester, 2006-2012
    *Lecturer in the PhD program*, “Bioinformatics in Medicine” The School of
    Medical Bioinformatics, Center for Medical Innovation: 1 scheduled hour per
    semester, 2002-2005.
    *Lecturer at the PhD program*, “An overview of the process of
    atherosclerosis” (# 1551) at the Karolinska University Hospital, Solna 1
    scheduled hour per year. “Systems biological approach to
    atherosclerosis”, 2005–2009.
    *Lecturer in the PhD program of Clinical Sciences at the Karolinska
    University Hospital, Huddinge*: “From gene to disease”. Atherosclerosis:
    Gen-protein function. 1 scheduled hour per semester, 2003–2005.
    *Lecturer in the Biomedical School, semester 6, “Molecular Medicine”, the
    Karolinska University Hospital, Solna:* 1 scheduled hour per semester,
    *“Your food intake is a matter of your heart”, Health care* at Karolinska
    Institutet, 2004, 2005, 2008.


All other publications


  • Principal Researcher, Department of Medicine, Huddinge, Karolinska Institutet, 2022-

Degrees and Education

  • Docent, Karolinska Institutet, 2003
  • University Medical Degree, Karolinska Institutet, 1995

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