Alan C. Mullen, MD, PhD
The Mullen lab investigates how long noncoding RNAs regulate human development and disease, and studies their function in liver fibrosis.
RNA is transcribed from most of the genome, yet only a small fraction of this RNA encodes proteins. More long noncoding RNAs have been annotated in the human genome than protein coding genes, and these numbers continue to increase as long noncoding RNA species are mapped in more cell types.
Our group studies how long noncoding RNAs regulate (1) the differentiation of embryonic stem cells towards definitive endoderm (the first step in development towards the liver and gastrointestinal system), and (2) liver fibrosis.
We use genetic approaches to study loss of function through RNA interference and gene disruption using the CRISPR-Cas system, and couple this with biochemical approaches to identify the partners that interact with these long noncoding RNAs.
In the liver, we study how long noncoding RNAs regulate the fibrotic activity of hepatic stellate cells, the primary cell type responsible for production of the fibrotic scar in chronic liver disease. Through these studies, we have also developed approaches to screen for compounds that inhibit the fibrotic phenotype in hepatic stellate cells as well as coding and noncoding genes that are required to maintain the fibrotic phenotype in hepatic stellate cells. These approaches will allow us to better understand the function of long noncoding RNAs and develop new therapies to inhibit liver fibrosis.