Dr Jesmond Dalli explains how his new research has uncovered enzymes that are crucial for the repair and regeneration of tissues, and could lead to new treatments for diseases such as rheumatoid arthritis.
Dr Jesmond Dalli is a Reader in Molecular Medicine at the William Harvey Research Institute. He is also a Sir Henry Dale Fellow and the Director of the Lipid Mediator Unit.
We recently uncovered a new family of macrophage-derived molecules, coined ‘maresin conjugates in tissue regeneration’ (MCTR), that regulate the system’s ability to clear bacteria as well as repair and regenerate damaged tissues.
This research identifies the enzymes responsible for the formation of molecules that are central for the repair and regeneration of tissues.
The results, therefore help us to better understand why in certain situations the body is no longer able to repair and regenerate tissues, such as after a bone is broken. This knowledge could be applied, for example, in diseases such as rheumatoid arthritis, where the joints are constantly eroded away.
This could have a big impact on society since it can help us design ways to increase the repair of tissues by increasing the expression of these enzymes and identify why some people heal better than others. This would help us design treatments that are more effective.
We think that measuring the expression of these enzymes as well as their products, the MCTR, can help us better treat conditions where damaged tissue does not heal in an effective manner. We will be further investigating this possibility in mice and in humans.
The research was conducted using cells from humans as well as state-of-the-art techniques to measure the activity of enzymes and identify and quantify the products that they produce. We also used this methodology to identify these molecules in the human body, specifically human blood and lymph nodes.
This helped us to identify the enzymes involved in the formation of these potent molecules in human macrophages. These enzymes were also found to be shared with the classic cysteinyl leukotrienes, underscoring the presence of conserved biosynthetic motifs in these two functionally distinct lipid mediator families.
This work was initiated in Boston at Harvard Medical School and the Brigham and Women’s hospital, and funded by the National Institutes of Health (USA) and the European Research Council.
Research paper: Maresin Conjugates in Tissue Regeneration Biosynthesis Enzymes in Human Macrophages. Jesmond Dalli, Iliyan Vlasakov, Ian R. Riley, Ana R. Rodriguez, Bernd Spur, Nicos A. Petasis, Nan Chiang, Charles N. Serhan. Proceedings of the National Academy of Sciences 2016.