Project Title: Hedgehog acyltransferase: a potential therapeutic target in pancreatic cancer
Research Aims: Professor Magee is interested in a group of proteins called ‘Hedgehogs’. These are normally found directing the growth of embryos, for example they send signals to instruct which cells to grow into different body parts. However, the sequence of signals (known as a ‘signalling pathway’) activated by Hedgehog proteins is also active in 70% of pancreatic tumours, wrongly promoting cell growth.
The Hedgehog signalling pathway is active in tumours because an enzyme called ‘Hhat’ coats the proteins in fats, allowing them to stick to healthy cells. When they stick they cause the healthy cells to release molecules which in turn promote tumour growth. Professor Magee is working to stop Hedgehog molecules from being coated in fats, ultimately preventing tumour growth.
Currently, drugs are being developed by pharmaceutical companies that prevent healthy cells reacting to the Hedgehog signal they receive from tumour cells. Although this can be good for treating tumours, it prevents the surrounding normal tissue from growing, and also tumours can become resistant to the drugs.
Professor Magee’s work is focused on a different part of the signalling pathway. He believes that targeting Hhat instead of Hedgehog signalling would limit not only the growth of the tumour, but also its spread to healthy tissue.
His team believes Hhat may be a potential drug target to treat pancreatic cancer. This treatment would be complementary to the drug therapies developed to target Hedgehog signalling directly. Professor Magee will also look at potential ways of finding molecules that stick to Hhat to prevent it from working. If successful this may lead to the development of new drugs.