Preventing Liver Fibrosis with Therapies Derived from Long Non-coding RNAs

Alan Mullen, MD, PhD
Alan Mullen, MD, PhD
MGH Research Scholar 2022-2027
Physician Investigator, Division of Gastroenterology
Associate Professor of Medicine, Harvard Medical School

Chronic liver injury leads to fibrosis, the primary cause of liver failure in the setting of any chronic liver disease. My lab focuses on developing approaches to treat liver fibrosis by identifying long non-coding ribonucleic acids (lncRNAs) that promote fibrosis and blocking their activity.

LncRNAs are a class of RNAs that do not encode proteins, and there are many more genes encoding lncRNAs than genes encoding proteins. In addition, most lncRNAs in humans do not have an equivalent gene identifiable in rodents, so we need human cell models to understand the activity of many lncRNAs relevant to human disease.

We have studied lncRNAs enriched in human hepatic stellate cells, the primary cell type responsible for liver fibrosis, and developed computational tools to search single cell data for additional lncRNAs associated with human liver disease.

We also have demonstrated that we can disrupt lncRNA genes in human pluripotent stem cells and differentiate these cells into mini livers called liver organoids to understand how loss of human lncRNAs regulates how liver cells respond to injury and fibrosis.

The MGH Research Scholar award will support combining these approaches, allowing us to determine how human lncRNAs control the development of fibrosis and can be targeted to prevent liver failure.