Scott Cao, M.D.

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SUMMARY

Alcoholic hepatitis (AH) in its severe form is an acute condition that requires early recognition and specialized tertiary medical care. It is most likely to occur in people who drink heavily over many years. However, the relationship between drinking and AH is complex. Sheng (Scott) Cao, M.D., and his colleagues are studying the cause of the gradual destruction of the liver in this disease.

Focus areas

• AH. Dr. Cao's lab has developed the most up-to-date technology, CRISPR-dCas9, which uses genomic DNA site-specific gene editing techniques, to regulate specific gene expression under enhancers and superenhancers. The use of these techniques can significantly advance research and clinical practice, particularly in the field of AH. Dr. Cao and his colleagues are currently studying the cause of gradual liver destruction in liver diseases, in particular AH, a highly morbid condition characterized by acute liver injury in the setting of excess alcohol ingestion. Severe AH can lead to acute liver failure and is associated with a 30-day mortality of greater than 30%.

  Many cytokines and chemokines are known to be highly upregulated in AH, of which tumor necrosis factor-alpha (TNF-alpha) is a prototypical example. TNF-alpha is highly induced in AH and released by inflammatory cells, possibly Kupffer cells in the liver. TNF-alpha is a trigger for other chemokines in propagating the inflammatory cascade. However, the downstream signaling pathways and regulatory mechanisms related to TNF-alpha signaling remain incompletely understood despite decades of research. Dr. Cao's work has suggested that TNF-alpha may regulate expression of target inflammatory genes via activation of superenhancers. He found a superenhancer that modulates the expression of CXCL chemokines in AH under TNF-alpha stimulation in hepatic sinusoidal endothelial cells, and both the superenhancer and its target genes are under control of histone modifications. This work highlighted the important roles of distal cis-regulatory elements and epigenetic regulation, or lack thereof, in the pathogenesis of AH.

• Cirrhosis of the liver. Cirrhosis is scarring of the liver that involves the formation of fibrous tissue associated with the destruction of the normal architecture of the organ, which prevents the liver from functioning normally. It is a serious disease, as only 30 percent of patients with cirrhosis survive five years after diagnosis. Based on Dr. Cao's research, it may be possible to find new treatments for patients with alcohol addiction and chronic hepatitis B virus infection, as well as chronic hepatitis C virus infection, in the future.
• Next-generation sequencing (NGS). Dr. Cao analyzes NGS datasets side by side with Mayo Clinic's bioinformatics personnel to develop new approaches with NGS datasets, many of which have been, or will be, published. His strong common sense and organizational skills facilitate new science and technologies.

Significance to patient care

If treatment is started early, patients with AH have better outcomes, which is the ultimate aim of Dr. Cao's research.

Professional highlights

• Reviewer, Hepatology, 2011-present
• Reviewer, Journal of Hepatology, 2009-present
• Reviewer, Arteriosclerosis, Thrombosis and Vascular Biology, 2009-present
• Reviewer, Journal of Molecular and Cellular Cardiology, 2009-present
• Member, Federation of American Societies for Experimental Biology, 2009-present
• Editorial board member, Nitric Oxide, 2007-present
• Reviewer, Journal of Cellular Physiology, 2007-present
• Member, American Association for the Study of Liver Diseases, 2004-present
• Reviewer, Lipids, 2004-present
• Reviewer, PLOS One, 2004-present
• Member, American Society for Biochemistry and Molecular Biology, 2001-present
• Member, American Association for the Advancement of Science, 1999-present