Klaudia Kaczmarek: Inhibiting PMRTs in Asthma
Klaudia Kaczmarek is a PhD student working in Nottingham City Hospital, supervised by Professor Alan Knox and Dr Rachel Clifford. Her project is aimed to find new targets for the development of novel drugs to treat severe asthma.
DNA is compacted into the cell nucleus by wrapping around proteins called histones. Histones are able to undergo modifications, which can “switch the genes on and off”. One of these modifications, called histone arginine methylation, is likely to be abnormal in patients suffering from asthma. We think that this abnormality may be responsible for the increase in the secretion of inflammatory chemicals from airway smooth muscle cells, which make up the muscles surrounding the airways. The resulting airway inflammation is one of the reasons why asthma patients suffer from symptoms such as coughing and wheezing.
If we prove that abnormal histone arginine methylation increases the inflammation in asthmatic airways, we will be able to target it with new compounds, as histone modifications are reversible.
Histone arginine methylation is carried out by the enzymes called PRMTs. We are testing whether by using currently available compounds that inhibit the action of PRMTs, the release of inflammatory chemicals from asthmatic airway smooth muscle cells can be reduced. This project also aims to develop new, better compounds that inhibit PRMTs, which could potentially be used in the treatment of asthma.