Leveraging rare genetic variation to understand the role of Liver X Receptor in human glucose and lipid metabolism

Genes are the instruction manual of our cells. They contain the code (in the form of DNA) that enables our cells to make all that is necessary to function. Small changes in our genes can have a large impact on our risk of disease. This is well known for rare inherited diseases like cystic fibrosis.

However, it is also the case that a proportion of common diseases, like Type 2 diabetes and cardiovascular disesae, may be the result of damaging mutations in certain genes.

Liver X Receptor-alpha (LXR-alpha) is a protein that senses cholesterol in our liver and fat tissue, however, it is unclear if LXR-alpha has any effect on blood sugar or the lipids in our blood.

We will identify humans in population biobanks with rare changes that effect Liver X receptor function and compare them to those who do not carry these changes to help inform the function of Liver X Receptor in humans.

We will use bespoke mouse models with a specific loss of function mutation in Liver X Receptor and cell models grown in test tubes to probe the specific mechanisms that underlie the effects of Liver X Receptor identified in human studies.