Research

Our research is focused on

  • The endothelium- a secretory organ regulating cardiometabolic physiology and pathology.
  • Transcription factor Prox1 as a regulator of skeletal muscle stem cell differentiation and metabolism.
  • Identifying genetic determinants of congenital heart diseases.

 

Endothelium as a secretory organ

Cardiovascular diseases rank among the most life-threatening diseases and are a continuously increasing global problem in aging populations. Despite some progress in treatment options, the clinical prognosis of heart failure is currently worse than that of most cancers.

Endothelial cells in different organs have been shown to express a unique combination of transcription factors, angiogenic growth factors, adhesion molecules and chemokines. This reflects the varying needs of different organs for e.g. oxygen and nutrient supply. In response to different stimuli, ECs secrete a set of proteins, which can act on the various neighbouring cell types. It is estimated that humans have about 100000 km of blood vessels, which most likely makes the vasculature the largest endocrine organ in the body.

Our research is focused on studying how endothelial cell transcriptome and secretome is changed by common cardiometabolic risk factors such as aging, physical inactivity and obesity. Our aim is to identify novel targets in endothelial cells for cardiovascular diseases.

 

transcription factor prox1 regulating skeletal muscle physiology and pathology

Unlike the heart, skeletal muscles have a remarkable capacity for regeneration. We have shown that Prox1 transcription factor, which regulates stem cell behaviour in various healthy and malignant tissues, is essential for slow muscle fiber type and satellite cell differentiation in skeletal muscle (Kivelä et al. Nature Communications 2016). Interestingly, several genome-wide association studies have also identified Prox1 as one of the strongest candidate genes in type 2 diabetes in various populations.

We explore the mechanisms and the relationship between Prox1, metabolism and type 2 diabetes. Further studies on Prox1 mediated regulation of muscle stem cell (satellite cell) differentiation will be important for promoting muscle regeneration and to understand its function in stem cells and in cancer.

 

genetic determinants in congenital heart diseases

Congenital heart defects are the most common birth defects affecting nearly 1% of newborns. Although it is clear that in many cases there is a genetic component involved, the inheritance is complex. Finding genetic variants causing these defects has been difficult, even in families with multiple affected members. Identifying genes and molecular mechanisms behind congenital heart diseases would provide additional tools for prenatal and genetic counseling and increase our understanding the complex molecular mechanisms of heart development in general.

We examine genetic determinants of congenital heart disease in a Finnish patient population using next generation sequencing, CRISPR/CAS9 gene editing technology, and patient-derived induced pluripotent stem (iPS) cells.