Association between age-associated DNA mutations and atherosclerotic disease risk

It is well recognized that acquired genetic mutations are an important cause of cancer, but recent studies have suggested that such somatic mutations are also associated with atherosclerosis. Somatic mutations have been found in blood from 10% of people over 70 years of age and 20% of people over 90 years of age and appear associated with an increased risk of atherosclerotic disease. Although age is a known independent risk factor for atherosclerosis, the basis for this has not been known.  It now appears likely that these mutations, several of which are found in genes known to regulate inflammation and immunity, are either a direct contributor to, or a potential biomarker for, this age-associated risk. The challenge now is to identify molecular mechanisms linking these somatic mutations with atherosclerosis.

This PhD project will investigate the cellular and molecular basis of the association between age associated DNA mutations and atherosclerotic disease risk. To do this will require cross-disciplinary collaboration, so this project brings together two highly complementary groups to address this important new biomedical challenge. At the National Heart, Lung and Blood Institute of the NIH, Chris Hourigan works on these acquired mutations in the context of a blood cancer called acute myeloid leukemia. At Oxford, Chris O’Callaghan works on molecular mechanisms involved in atherosclerosis and the genetic control of those mechanisms, especially in vessel wall inflammation.

This is a very exciting new field and has potential to identify new drug targets and so benefit patients with atherosclerosis. The experience gained by this doctorate will be highly relevant to other fields and will include cellular and molecular biology, high throughput sequencing approaches including single cell approaches and analysis of genetic variation.

*This project is available for the 2021 Oxford-NIH Pilot Programme*