About me

Research group leader of the group Vascular Surgery

Research description

Background

Apart from cardiac embolism, most ischemic strokes occur as a consequence to end-stage atherosclerotic disease. Atherosclerosis leads to formation of plaques in the intima of major arteries with accumulation of lipids, inflammation, fibrosis, cell death and calcification. Stable lesions are generally asymptomatic but when plaques become unstable from enhanced inflammation and proteolysis, destabilization of the fibrous cap may lead to plaque rupture, thrombosis (atherothrombosis), embolism and cerebral ischemia. More than 50% of ischemic strokes are caused by thromboembolism from extracranial vessels, as unstable plaques in the carotid bifurcation. The condition can cause transient ischemic attack (TIA), retinal symptoms (amaurosis fugax) or complete stroke. The significance of this process has been confirmed in studies demonstrating that surgery for carotid stenosis, carotid endarterectomy (CEA), in patients with symptomatic (unstable) lesions prevents stroke. Today, there are no diagnostic methods available to predict or identify plaque rupture and thus to prevent stroke from unstable atherosclerosis. Selection of patients for intervention instead rests on surrogate variables for stroke risk, such as the degree of luminal narrowing by the stenosis. In our unit, approximately 60-70 symptomatic patients undergo CEA annually, >85% within two weeks after index event (national guideline), and with an estimated efficacy of 10 prevented strokes whereas 10-15 asymptomatic patients undergo CEA with less than one prevented stroke estimated.

Work plan

This project is based on current studies utilizing an established biobank (BiKE) of plaque and plasma samples from n>800 patients treated at our clinic, which have been prospectively processed for RNA, DNA, proteomic, in situ and in vitro analyses. The biobank is combined with data of phenotypic information, transcriptomic array profiles and genome wide SNP data. The resource has progressively developed and over the years been extensively utilised to identify gene signatures in atherosclerotic plaque instability. The project is currently being expanded to include large-scale characterization of plasma- and tissue proteins as well as non-coding RNAs (miRs) of human atherosclerosis in correlation to transcriptomic profiles, ultimately aiming at detection of plausible biomarkers for unstable end-stage atherosclerosis. Through established collaborations with international and national resources (SciLife; SCAPIS; Göteborgs Universitet; Stanford; King’s College, London), we are implementing state-of-the-art proteomics (mass spectroscopy and affinity-based) of plasma- and tissue samples from patients with stable- and unstable carotid stenosis, next generation methodology for RNA expression analyses in situ, and pre-operative imaging of patients with new MRI- and ultrasound based technology with the ultimate goal of developing targeted bioimaging for the localization of unstable atherosclerotic lesions. 

Aims

Through the identification of circulating signature molecules (biomarkers) for the unstable atheroma and the development of diagnostic tools for morphological characterization of unstable carotid plaques this project will improve stroke-prevention by:

optimizing risk intervention improving selection of patients for stroke preventive surgery and supporting development of plaque-stabilizing drugs

Teaching portfolio

Huvudhandledning                 Joy Roy, MD PhD                                                                010831

                            Piotr Religa, MD PhD                                                      030214

                            Monsur Kazi, MD PhD                                                     030328

                            Kiet Tran, MD PhD                                                            050218

                            Karin Tran Lundmark, MD PhD                                 080307

                            Anton Razuvaev, MD PhD                                            090603

                           

                            Jing Wang, post-doc                                                        2008-2010

                            Cecilia Österholm-Corbascio post-doc              2010-2014

                            Ljubica Perisic, post-doc                                             2012-

                            Silvia Aldi, post-doc                                                         2014-

                            Linnea Eriksson, post-doc                                           2014-

 

Bihandledning                           Chi-Nan Tseng, MD PhD                                                150410

                            Ya Ting Chang, MD PhD                                                  150612

                            Carl Montán, MD PhD                                                    150529

                            Alireza Daraypeyma, MD PhD                                  150424

                           

Undervisning                Kursarrangör Forskarutbildningskurser 6st

                                              Kursarrangör ST utbildningskurser Kärlkirurgi 16st

Studierektor Biomedicinarprogrammet Molekylär Medicin, KI 1996-1998; bitr Studierektor Biomedicinarprogrammet Molekylär Medicin, KI 1999; Utbildningsansvarig Läkarprogrammet Kärlkirurgi 1997-2003

                                              Handledning projektarbeten Läkarprogrammet, KI 13 studenter

Education

Högskoleexamen                     Karolinska Institutet, Läkarutbildningen, 1985

Doktorsexamen                        Karolinska Institutet, Medicinsk Cellbiologi, 1989

Postdoktorvistelser                Post-doc: Senior Vascular Fellow Dept Surgery, Div Vascular Surgery, Univ Washington, Seattle, USA, 1995-1996

Docentkompetens                  Docent, Karolinska Institutet, 1994

Specialistexamen                    Kirurgi, 1997; Kärlkirurgi, 1997 (efter tillkomst av grenspecialitet)

Nuvarande anställning          Professor/överläkare, Kärlkirurgiska sektionen, Institutionen för molekylär medicin och kirurgi, Karolinska Institutet samt Kärlkirurgiska kliniken, Karolinska Universitetssjukhuset, Solna.

Gruppledare , Vascular Surgery Research Group , Institutionen för molekylär medicin och kirurgi Solna , Karolinska Institutet.

Tidigare befattningar             Utbildningsbidrag KI 1985-09-01 till 1988-06-30; Doktorand-tjänst, KI 1988-07-01 till 1989-11-01; Stipendium vid MFR för övergång till klinisk forskning 1991-1993; Forskarassistenttjänst i Molekylär Medicin, Karolinska Sjukhuset/Institutet 93-97 (50%); Särskild forskartjänst (lektor 50%) kardiovaskulär forskning Hjärt- Lungfonden 1998-2004; Universitetslektor/Överläkare Kärl-kirurgiska kliniken, Karolinska Sjukhuset 2001-03-01; Biträdande prefekt, MMK, Karolinska Institutet 2005-2009; Förslag professor vaskulärbiologi , Linköpings universitet , 2001; Förslag professor i kirurgi , Kings College , London , Storbritannien, 2009; Verksamhetschef Kärlkirurgiska kliniken, Karolinska Universitetssjukhuset 2010-2016

Academic honours, awards and prizes

Förtroendeuppdrag               Styrelseledamot: Scandinavian Society for Atherosclerosis Research 1994-1999; Inst Kir, KI/KS 2001-; Beredningrupp VR 2000-2006; SPESAK Stockholms län (SLL) 2006-2011; Nationell representant European Society for Vascular Surgery 2008-2011; Forskningsrådet Hjärt-Lungfonden 2011-2015; International Surgical Group 2011-; Forskningsrådet Lundbeck Foundation 2012 -; Elektor VR 2015; Valberedning VR 2015; Nominerad Prefekt Inst Mol Med Kir, KI 2016; Socialstyrelsens Prioriteringsgrupp Strokeriktlinjer 2016.

Sakkunniguppdrag                   Extern sakkunnig: Docentur: Lunds Universitet 6 st; Sahlgrenska Akademin 2 st; KI 8 st. Uppsala Universitet 1 st. Lektorat: Lunds Universitet 2 st. Professur Kärlkirurgi: Köpenhamns Universitet 2013; Syddansk Universitet 2012; Helsingfors Universitet 2014; Lunds Universitet 2015; Harvard Medical School 2015. Söderbergska Priset, Svensk Kirurgisk Förening 2013. Syddansk Center of Excellence 2015.

1.          Fakultetsopponent: 15 st (Yenfeng Wang, Wihuri Res Inst, Helsinki, Finland, 1999; Lars Lohikangas, Uppsala Universitet, Uppsala, 2000; Audrey Niemann-Jönsson, Lunds Universitet, Malmö, 2000; Sara Moses, Lunds Universitet, 2002; Marie-Louise Moes Grönholdt, Rigshospitalet, Köpenhamn, Danmark, 2003; Helena Peilot, Sahlgrenska Akademin, Göteborg, 2003; Per Fogelstrand, Sahlgrenska Akademin, Göteborg, 2004; Andreas Bergdahl, Lunds Universitet, 2004; Nikolaj Eldrup, Köpenhamns Universitet, 2008; Per Wastesson, Sahlgrenska Akademin, 2008; Niklas Bergh, Sahlgrenska Akademin, 2009; Tomas Block, Uppsala Universitet, 2010; Martin Graebe, Köpenhamns Universitet, 2010; Louise Rosenörn de la Motte, Köpenhamns Universitet, 2013; Charlotte Eklund, Göteborgs Universitet, 2014); Halvtidskontroller 24 st; Betygsnämnd 22st

2.                                 Referee 17 Tidskrifter

Utmärkelser                                Forskargrupp graderad ’excellent’ efter internationell utvärdering av alla forskargrupper vid Karolinska Institutet

2013 Harry Broström Memorial Lecture, Svenska föreningen för invärtesmedicin