Current Research Projects



1. Global effects of maternal smoking on the human fetal liver protein profile

Dr Panagiotis Filis at the University of Aberdeen

What is this study looking at?

This study is exploring how different factors during pregnancy can affect how the liver develops.

This study is investigating the types and numbers of proteins which are present in the livers of foetuses (unborn babies). It will look at how the proteins present in the livers of foetuses can be affected by age, gender and by the mother smoking during pregnancy.

Why is this research important?

The foetal liver plays many important roles during the development of the foetus. Previous research has shown that smoking may disrupt chemical pathways in the liver which could contribute toward the development of diseases such as non-alcoholic fatty liver disease (NAFLD). It is hoped that this study will help us to understand more about how the liver can be affected in pregnancy.

What about the future?

If this study is successful it will lead to further studies aiming to identify characteristics in newborns which can tell us if a child has a predisposition to liver disease, i.e. a characteristic which mean it’s more likely for newborns to develop liver disease.

 

2. Congenital porto-systemic shunts and the development of liver tumours: characterisation of the genetic and histopathologic background to identify the progression of molecular alterations

Professor Richard Thomas. Joint with BSPGHAN.

What is this study looking at?

Congenital porto-systemic shunts (CPSS) occur when the blood vessels around the liver aren’t formed properly so the blood doesn’t flow through, in and around the liver as it should.

In some cases of CPSS blood from the intestines, pancreas and spleen which feeds into the liver (called portal venous blood) bypasses the liver straight into the main blood circulation in the body. In other cases blood from the hepatic artery may take on the role of supplying nutrients to the liver instead of the portal vein.

These changes can affect the chemical balance inside the liver. It isn’t know exactly why, but people who have CPSS are more likely to develop tumours. This study aims to find out why this is. The team will look at the microscopic appearance of the liver to see what changes there are as well as looking at genetic changes in the livers of patients with CPSS.

Why is this research important?

There hasn’t been a huge amount of research done on this topic in the past and it is hope that by understanding why individuals with CPSS are more likely to develop tumours and how these tumours are formed, we may be able to treat these patients more effectively in the future.

What about the future?

If the study is successful the researchers will know more about the formation of tumours in CPSS and hope to develop a method to screen patients with CPSS so they are able to tell how likely it is that a tumour will spread (be malignant) which will help clinicians to treat it more effectively.

 

3. Association of stool microbial profile with short-term outcome in infants with biliary atresia after Kasai Portoenterostomy

Dr Vandana Jain at King’s College Hospital, London

What is this study looking at?

Biliary atresia (BA) is a disease in children where inflammation within the bile ducts lead to jaundice and liver inflammation. An operation called a “Kasai-Portoenterostomy” (Kasai) can be performed in the first two months of life to “re-plumb” the liver to the gut to restore bile flow between the liver and the gut.

It is thought that microorganisms (such as bacteria, viruses, and fungi) within the gut may have an impact on how serious liver disease in children with BA becomes. The research team will look at the microorganisms inside the guts of children who have had the Kasai at different ages.

The team will then compare which microorganisms are present in the guts of children who have BA but are healthy after the Kasai procedure, those with BA who have the procedure but need a liver transplant afterwards and healthy children without biliary atresia.

Why is this research important?

The impact of microorganisms in the gut has been studied in adults with liver disease and is believed to play a role in adult liver disease. Until now there has been little research into its potential role in biliary atresia. This research will further our knowledge and understanding of whether microorganisms have a role in paediatric liver disease.

What about the future?

It is hoped that we will be able to find out if microorganisms inside the gut play a role in making liver disease worse in biliary atresia, and if so, which ones.

If microorganisms are identified the next step is to find out how to target these bacteria so we can reduce the number of harmful bacteria in the guts of biliary atresia patients. Potential treatments may include antibiotics, diet or probiotics.

 

4. Investigation of myofibroblast αv integrins as an anti-fibrotic target in biliary atresia and fibrosis

Dr Neil Henderson at the University of Edinburgh. A joint project with the charity CORE.

What is this study looking at?

Myofibroblasts are a type of cell within the liver which cause scar tissue during biliary fibrosis (scarring of the bile ducts). These cells are a target for researchers to find out more about, to understand how the scarring occurs.

In order to find out which molecules in myofibrosis might be responsible for causing scarring during biliary atresia, the team will use genetically modified mice that allow them to remove specific molecules within myofibroblasts to see what impact this has on scar formation in the mice.

Integrins are molecules which allow cells to communicate with each other and also with areas of scar within the liver. The researchers will use genetically modified mice to remove a specific integrin, the alpha v integrim, from myofibroblasts to find out whether this stops scarring from occuring. They will also treat mice with a new drug (CWHM12) that blocks alpha v integrins to see whether this drug can protect mice from biliary fibrosis. Additionally, they will also isolate liver myofibrosis from patients with biliary atresia and assess whether CWHM12 can switch off scar-producing genes in these cells.

Why is this research important?

Biliary atresia is a condition which causes inflammation and destruction of children’s bile ducts and can lead to biliary fibrosis (scarring of the liver), liver failure and death. When biliary fibrosis becomes severe, the liver begins to fail and currently our only available treatment for end-stage liver scarring is liver transplantation. This research aims to find out whether treatments targeting integrins within myofibrosis could treat biliary atresia.

What about the future?

If the researchers find that these key molecules play a role in the scarring of the bile ducts they will be able to look at drugs which could target these and prevent the scarring and possibly offer an alternative to liver transplantation in the future.

 

5. Optimising drug regimens in paediatric liver disease using experimentally-derived simulation tools

Professor Amin Rostami and Dr Jill Barber at the University of Manchester

What is this study looking at?

This research is exploring how medications act in children’s livers including those which a liver disease. Livers vary from person to person and these differences can affect how much of a drug a child should be given. Size of liver is one important variation and another is the level of different enzymes in the liver. The enzymes help different reactions take place in the liver including the breakdown of medications. The research team have developed a way to measure the level of enzymes in livers. They will be looking at livers from children with and without liver disease and comparing the levels of a number of different enzymes.

Why is this research important?

At the moment it is very difficult for doctors to know exactly how much of a drug a child should be given. This means they have to try and estimate dosages based on adult amounts.

What about the future?

The results of this study will feed into a model which will help doctors prescribing medicines to children with liver disease to prescribe the most suitable dose.

 

6. Bilibaby: an ongoing project to develop a screening test to be able to detect bilirubin in stool to screen for childhood liver diseases

Professor Alastair Sutcliffe at King’s College London

What is this study looking at?

This study is looking into ways to identify biliary atresia (BA) in newborns by looking at the stool (poo) of babies born with BA. The researchers have produced a testing stick which can test stool for neonatal cholestasis. The stick changes colour from colourless to pink when no problem is detected with the stool but remains colourless when there is a problem with bile flow.

This funding has been awarded to enable further testing of the stick. Nurses at King’s College London will collect stool samples from all babies with BA over a 6 month period, as well as from other babies to test the accuracy of the stick.

Why is this research important?

At the moment healthcare professionals use their judgement to tell whether or not a stool is a healthy colour or whether it is pale, which could be a warning sign of liver disease. Sometimes this can be difficult as it is a very subjective process. The stick would allow midwives to test all babies’ stool and would tell midwives whether or not the baby may have a problem with their liver due to a reduced bile flow.

What about the future?

If the study is successful the research team will look to develop and produce the testing stick which will help healthcare professionals to identify diseases such as BA in newborns at an early stage in order to improve the outcome for patients with BA.

For details of all research projects we have previously funded click here.