At the center of the obesity epidemic is the metabolic syndrome - a cluster of conditions defined by excess body weight and the dysregulated processing of sugar and lipids (fats and cholesterol). As many as one in three Americans may be at risk for this syndrome, which is considered to herald the leading causes of death: diabetes, heart disease, and stroke. The liver is the workhorse organ for metabolism, so it is no surprise that metabolic syndrome is also closely associated with chronic liver disease. Understanding the relationships among metabolic syndrome and progressive liver disease, inflammation, scarring (fibrosis), and eventually cirrhosis could lead to novel treatments for this fundamental health problem.
The metabolic syndrome research conducted within COMET, is led by Dr. Simon Beaven. It focuses on how alterations of lipid metabolism promote liver damage and insulin resistance/diabetes. The team studies the role of endogenous nutrient receptors, called nuclear receptors, on the development of the component conditions of the metabolic syndrome: fatty liver, diabetes, dyslipidemia (high cholesterol), obesity, and atherosclerosis. Of particular interest is how altered lipid metabolism contributes to the liver's wound-healing response. In the face of any chronic injury, the liver generates scar tissue, a process known as fibrosis, which is mediated by a specialized liver cell called the hepatic stellate cell. Left unchecked, fibrosis can progress to cirrhosis (end-stage liver disease), the need for liver transplantation, and a dramatically reduced lifespan. Currently, there are no anti-fibrotic therapies that specifically target hepatic stellate cells in any liver disease.
Recently, Dr. Beaven made a major breakthrough with the observation that lipid metabolism, through liver X receptor (LXR) signaling, plays an important role in the activation of hepatic stellate cells and contributes to liver fibrosis susceptibility. This unexpected finding has opened up a new field of study - cholesterol metabolism in liver wound healing. A better understanding of how this scarring process occurs could lead to new approaches for slowing or halting the progressive fibrosis that is at the root of all chronic liver diseases, including the metabolic syndrome.
List of active clinical trials and studies
Our clinical program for fatty liver
Dr. Clark attended Cornell University, earning highest honors in chemistry, high honors in biology, and honors in mathematics. Dr. Clark earned his PhD in chemistry from the California Institute of Technology where he received the Herbert Newby McCoy Award in Chemistry. His graduate work focused on the post-translational modification N-acetyl-D-glucosamine, which has been implicated in diseases such as diabetes and Alzheimer's disease. Dr. Clark now works as a post-doctoral scholar in the laboratory of Dr. Owen Witte.
Dr. Clark's research focuses on using the molecular imaging technique positron emission tomography (PET) to improve the diagnosis and understanding of human diseases. His current focus is on the sugar ribose, which is important for the structure of RNA but which is also present in the diet and blood.Using a new PET imaging probe that he developed, Dr. Clark has shown that ribose metabolism is dysregulated in mouse models of metabolic syndrome.
Dr. Hong received her doctoral degree in biomedical engineering from UCLA in 2008. Subsequently, she completed a post-doctoral training under the mentorship of Dr. Peter Tontonoz in the Howard Hughes Medical Institute and UCLA's Department of Pathology and Laboratory Medicine. Her work focused on understanding the underlying biological mechanisms of cholesterol homeostasis and how molecular perturbations to this balance impact metabolic diseases.
In 2012, Dr. Hong joined the Department of Pathology and Laboratory Medicine's research faculty where she continues to address questions focused on lipid and sterol metabolism. In 2014, she received the Roger Davis Investigator Award for Transitional Faculty in lipid metabolism. Dr. Hong has received independent funding from the American Heart Association, the American Diabetes Association, Center for Ulcer Research and Education (CURE) and UCLA/UCSD Diabetes Research Center (DRC).
Dr. Raman is an expert in abdominal and pelvic imaging (CT, MRI, US and X-Ray) and interventional radiology (image guided procedures), especially in the area of tumor ablation and fibroid treatment. He is director of the Abdominal Imaging Fellowship at UCLA, and co-director of the Fibroid Treatment Program at UCLA.
