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On the Hemostatic Pathway in Stroke: An Integrated Clinical and Experimental Study

 

 

 

 

Fig. 1. The blood clot stops the blood supply to an area of brain leading to ischemia and eventual apoptosis.

 

 

 

Christina Jern

Contact InformationList of Publications

 

Stroke is both the second leading cause of death and a major cause of disability worldwide. Stroke also imposes a great socioeconomic burden. Despite this, there are many gaps of knowledge regarding risk factors, treatment and outcome.
Ischemia is the most common cause of stroke and blood clot formation is a key mechanistic event in ischemic stroke (Fig 1). Our group is therefore interested in understanding the role of hemostasis in ischemic stroke. Our research includes both clinical and experimental methodologies and uses a “bi-directional” translational approach; that is to say that findings from our clinical studies are investigated further in the laboratory and vice versa. The main overall aim is to test the hypothesis that the hemostatic pathway is of importance for stroke incidence, stroke recurrence and/or post-stroke outcome, and to better understand the underlying molecular and genetic mechanisms associated with this pathway.

 

 

 

 

Fig. 2. The four most common etiologic subtypes of ischemic stroke

 

 

 

 

 

 

 

Clinical Studies
The cornerstone for our project is the Sahlgrenska Academy Study on Ischemic Stroke (SAHLSIS), a cohort of patients with ischemic stroke before 70 years of age and population controls. Even within the group of ischemic stroke, disease etiology shows heterogeneity (Fig 2). We are therefore studying the hemostatic pathway, both at the protein and genetic level, in the different subtypes of ischemic stroke. In collaboration with national and international partners, we are also studying stroke in other cohorts, and we participate in studies within the International Stroke Genetics Consortium (ISGC) and in a large multi-center genome wide association (GWA) study on ischemic stroke subtypes, the Stroke Genetics Network (SiGN) study. Our group also performs GWA studies on hemostatic protein levels.

Although stroke is traditionally associated with the elderly, recent studies show that stroke incidence is increasing in the young. While younger stroke patients have a low case-fatality, they face the risk of permanent disabilities and recurrent vascular events. We are therefore also performing a long-term prospective study of the participants in SAHLSIS with the aim of identifying biomarkers that predict outcome. In the future, the knowledge gained from this project may suggest novel targets for therapy and lay the foundation for individual risk profiling and secondary prevention of ischemic stroke.
(Click here for additional information about SAHLSIS)
(Click here for additional information about stroke and Stroke Centre West)

Experimental Studies

Liver Project
The liver plays a major role in producing proteins that are secreted into the blood, including factors involved in hemostasis. The mechanisms regulating the synthesis and release of these factors are therefore crucial for a functional hemostatic system and to avoid thrombus formation. Genetic variation in coagulation-related genes has previously been demonstrated to be associated with altered levels of these factors in plasma and with an increased risk of ischemic stroke. Tight regulation of these genes are thus of vital importance.

Epigenetics is an important field in modern medicine as it may help to combine and explain the relationship between an individual’s genetic background, environmental factors, and disease. Given that hemostatic factors are primarily produced in the human liver and epigenetic modifications can be tissue specific, we have recently initiated a project on human liver samples to complement SAHLSIS. Our aim is to identify genetic variants and DNA methylation signatures that are functional in regulating expression of genes involved in hemostasis. Novel findings from this project will be tested in SAHLSIS to determine whether they are associated to ischemic stroke, stroke subtype or outcome.

Functional Characterization of Genetic Variants
Molecular genetic studies are used to investigate functional mechanisms underlying any observed associations from the clinical findings (techniques include cell culture, reporter gene assays, electrophoretic mobility shift assays, chromatin immunoprecipitation etc).

Group members

Christina Jern, MD, PhD, professor, group leader
Tara Stanne, PhD, researcher

Maja Olsson, PhD, researcher
Anders Gummesson, MD, PhD
Petra Redfors, MD, PhD
Lukas Holmegaard, MD, PhD student
Annie Pedersen, MD, PhD student
Martina Olsson, MS, PhD student
Ingrid Eriksson, research nurse
Jenny Ödquist, research nurse
Sven-Öijvind Swahn, research engineer
 

 

Co-workers at the Institute of Neuroscience and Physiology
Katarina Jood, MD, PhD, group leader
Christian Blomstrand, MD, PhD, senior professor
 

Sidansvarig: Dan Baeckström|Sidan uppdaterades: 2016-09-28
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