Cellular stress signalling in the Bekker-Jensen Group

Our primary goal is to understand the contribution of cellular stress signalling pathways to a range of human diseases and aging processes. Our emphasis is on obtaining a deep mechanistic insight, while exploring opportunities for clinical translation of our findings.

Cellular stress signalling in the Bekker-Jensen Group

 

 

The overarching aim for our group is to understand the molecular details of cellular stress responses and how they contribute to human diseases such as cancer and aging-related maladies. We are especially interested in understanding the mechanisms by which the MAP kinases p38 and JNK become activated in response to cellular stress insults such as ribosomal impairment, oxidative stress and high osmolarity, and how such signaling drives or protect against pathological cellular changes. Importantly, the same signaling pathways are crucial for inflammatory responses, adding to the relevance of our work for a range of human diseases.

“The physiological and pathological outcomes of cellular stress signalling remain under-appreciated. I believe there is still much to be learned, and that our work can lead to medical breakthroughs,“ says Professor and Group Leader, Simon Bekker-Jensen.

 

Mechanisms of MAP kinase activation after diverse stress stimuli

The molecular mechanisms responsible for activation of p38 and JNK after stress stimuli are vastly understudied compared to the mechanisms governing activation of these kinases after extra-cellular receptor-mediated stimulation. In an attempt to fill this gap in our understanding of cellular stress responses, we are working to identify the unknown or poorly studied signalling components working upstream of MAP kinases. To this end, we employ siRNA screens and high-content microscopy techniques combined with a range of biochemical and cell biological techniques.

Identification of novel stress signaling pathways

Employing proteomics, we are continuously searching for new cellular target of p38 and JNK signalling. We have uncovered a number of such targets, and we are currently undertaking detailed investigation of their biological ramifications. Several of these projects focus on RNA-binding proteins, and regulation of post-transcriptional gene regulation is a common denominator for many effector pathways in cellular stress as well as inflammatory responses.

Requirement of cellular stress responses for cancer development and tumour cell maintenance

Cancer cells are more metabolically active than normal healthy cells, and consequently they have an increased requirement for functional stress signalling pathways to combat the detrimental effects of reactive oxygen species and other metabolic by-products. We hypothesize that these pathways will represent future targets for therapeutic intervention in cancer therapy. We are investigating these ideas in both cell culture and mouse models.

MAP kinase signalling as an anti-aging barrier

Exposure to low levels of various stress agents is known to benefit both healthspan and lifespan in model laboratory organisms (hormesis). We are actively engaged in studying the molecular basis of these effects, by genetic manipulation of longevity in the nematode C. elegans and mouse models.

 

 

 

Portrait of Simon Bekker-Jensen

Group leader:

Simon Holst Bekker-Jensen
Professor 

Email: sbj@sund.dk
Phone: +45 20 20 49 93

Twitter: @Bekkerjensenlab

CV, publications etc.

Members of the Bekker-Jensen group

Name Title Phone E-mail
Anna Constance Vind Postdoc +4535333474 E-mail
Goda Snieckute Postdoc +4535336532 E-mail
Laura Ryder Jordan PhD Fellow   E-mail
Melanie Blasius Associate Professor +4535334455 E-mail
Simon Holst Bekker-Jensen Professor +4535325024 E-mail
Zhenzhen Wu PhD Fellow   E-mail