Sven-Christian Pawelzik

Project description

Structure and Function of Microsomal Prostaglandin E Synthase 1

Eicosanoids are a group of biologically active lipids, which are are associated with a number of physiological functions, but also with pathophysiological states like allergy, asthma, chronic inflammation and cancer.

The eicosanoid Prostaglandin E2 (PGE2) represents an important mediator of inflammation. It has been connected with a number of different pathological states including inflammatory diseases such as rheumatoid arthritis. PGE2 is mainly formed by Microsomal Prostaglandin E Synthase 1 (MPGES1), which is upregulated by pro-inflammatory stimuli and acts in concert with Cyclooxygenase-2 (COX-2).

In my PhD projects I try to characterise the enzyme MPGES1 in terms of structure-function studies. By studying MPGES1 mutants I hope to understand the catalytic mechanism and identify the binding site for crucial substrates as well as newly developed inhibitors of MPGES1.

Besides that, I am involved in projects regarding Eicosanoid Metabolomics, i. e. the mass-spectrometry based quantification of all sorts of eicosanoids in all sorts of biological samples. During an inflammatory reaction the interplay of different bioactive lipids is of crucial importance. For instance, some of the prostaglandins act as pro-inflammatory agents whereas other prostaglandins have anti-inflammatory properties. Some mediators act positively on the circulation while others might cause blood clotting and cardiovascular diseases. Therefore it is important to know which mediators are formed, especially if it comes to inhibition of enzymes involved in formation of some of these compounds. In order to study this, I have developed methods for extraction and quantitation of lipid mediators applicable to biological samples.

Publications 

Microsomal prostaglandin E synthase 1 determines tumor growth in vivo of prostate and lung cancer cells.

Structural basis for induced formation of the inflammatory mediator prostaglandin E2.

Lymphoblastic T-cell lymphoma in mice is unaffected by Celecoxib as single agent or in combination with cyclophosphamide.Lymphoblastic T-cell lymphoma in mice is unaffected by Celecoxib as single agent or in combination with cyclophosphamide.