Haiming Cao, Ph.D.

The broad interest of the Cao group is to understand how regulatory RNAs control energy metabolism and how their dysregulation contributes to obesity and related disorders, including diabetes, fatty liver disease, and cardiovascular disease. Although most studies of metabolic regulation have focused on protein-coding genes, the human genome produces a vast and largely unexplored repertoire of long noncoding RNAs (lncRNAs). Defining the physiological functions of these molecules could reveal previously unrecognized mechanisms of metabolic disease and substantially expand the range of potential therapeutic targets.

A central focus of the laboratory is overcoming a major barrier to human lncRNA research: most human lncRNAs lack sequence conservation in commonly used animal models. The Cao group integrates human genetics, clinical transcriptomic data, long-read RNA sequencing, liver-specific humanized mice, and genetic mouse models to identify disease-relevant lncRNAs and define their functions under physiologically relevant conditions.

Recent work from the laboratory established the concept of functionally conserved lncRNAs—human and mouse lncRNAs that perform similar biological roles despite having little sequence similarity. The LMR1 study demonstrated that lncRNA function can be conserved through short RNA motifs and structural features rather than overall sequence, providing a new framework for studying human lncRNAs in animal models. Building on this concept, the GULL study showed that the biological activity of a lncRNA can be captured in a short functional RNA motif. This motif improved glucose and lipid metabolism in obese mice, providing proof of principle that functional elements derived from lncRNAs could be developed into compact RNA-based therapeutics.

The long-term goal of the Cao group is to define human RNA regulatory networks that govern metabolic homeostasis and translate these discoveries into new therapeutic strategies for obesity, diabetes, fatty liver disease, and their cardiovascular complications.

Videos

Haiming Cao, PhD, and his team won the Orloff Award for demonstrating the vital role of long noncoding RNA in metabolism and for developing a novel approach to study long noncoding RNA’s function in metabolic diseases. Watch Dr. Cao explain long noncoding RNA and his team’s work.

Haiming Cao earned his Ph.D. in biochemistry in 2003 from the University of Nevada Reno. He did his postdoctoral training at Harvard University from 2003 to 2010. Dr. Cao joined the NHLBI as an Earl Stadtman Investigator in 2011.