Center for the Study of Chronic Metabolic and Rare Diseases


The center's research is broadly focused on two major areas of study:
* Metabolic syndromes and obesity
* Rare Diseases.

Diseases Associated with Metabolic Sydrome and Obesity
Obesity has reached epidemic proportions. It affects every segment of the world population and continues to increase steadily, especially in children. A pro-inflammatory state (also referred to as low-grade chronic inflammation/meta-inflammation/sterile inflammation) associated with visceral obesity, has been also shown to be strongly correlated with the development of non-alcoholic fatty liver disease (NAFLD), and other chronic conditions, including type II diabetes, Coronary Artery Disease (CAD), and polycystic ovary syndrome all of which result in high medical costs, and decreases overall quality of life. Abnormal glucose metabolism and insulin resistance are major contributors to the diseases named above. Because of the complexity of obesity, it is likely to be one of the most difficult public health issues our society has faced.


Obesity related nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease (CLD) in the world NAFLD is associated with adverse cardiovascular outcomes. A proportion of NAFLD patients progress to nonalcoholic steatohepatitis (NASH) associated with liver related mortality and are in increasing numbers being referred for liver transplant (LT). Additionally, a variety of hepatotropic viruses, including hepatitis C, B and A work in concert with metabolic syndrome related NAFLD to hasten the progression of the virally induced liver disease to the cirrhosis that is, in turn, often associated with hepatocellular carcinoma (HCC) that is recently been linked to both NAFLD and viral hepatitis. This association is alarming due to the global high prevalence of these conditions and may contribute to the rising incidence of HCC witnessed in many industrialized countries. On top of clinical impact, chronic liver disease impairs patients' health-related quality of life (HRQL) resulting in significant morbidity. Because of the complexity of obesity, it is likely to be one of the most difficult public health issues our society has faced.

In order to address these challenges, CSCMRD has a team focused around a central research theme of Chronic Liver Disease. The focus of the Center relies upon the expertise that currently exists in the two institutions, namely clinical expertise of Inova as lead by Dr. Zobair Younossi and functional genomics expertise of multiple faculty affiliated with various departments at GMU.

In particular, the faculty and the students of CSCMRD explored the world of various molecules secreted to the bloodstream. The evidence of the metabolic cross-talk between human tissues is widespread. Adipokines produced by white adipose tissue possess broad physiological activity. Other tissues, particularly stomach and intestine, produce the molecules that can influence the function of adipocytes and, possibly, the levels of adipokine secretion. In some cases, the production sites of these molecules remain unknown. Very often, the same molecule may exert either beneficial or harmful effects, depending on the tissue and its local conditions. We also study circulating miRNAs that have received increased attention as potential diagnostic and prognostic biomarkers that could be accessed in minimally invasive way in a number of chronic diseases. Unexpected stability of miRNAs in circulation hints at the presence of a signaling pathway in which miRNAs are selectively secreted by one cell and taken up by a distant, target cell, possibly to regulate gene expression.

Rare Diseases Research

There are over 7000 estimated rare diseases known to the community of which over 100 diseases are due to inborn errors in metabolism. About 80% of all rare diseases are believed to have genetic cause and a majority of them are estimated to be monogenic. The OMIM database hosted by NIH, database from European Union and Globalgenes are some organizations that maintain databases of rare diseases. CSCMRD will study rare diseases with metabolic components including mitochondrial diseases. Objectives of the research projects will include: Objectives of the research projects covered under expansion into Rare Diseases area include:

* Discovery and systematic targeting of the metabolic components of rare diseases
* Understanding the mechanisms underlying metabolic components of genetic and chronic disease.
* Exploring palliative options such as nutritional supplements or enzyme replacements for the treatment of rare diseases.
* Uncovering relationship between common diseases and rare diseases, including participation of the recessive alleles for monogeneic disease in the development of the chronic disease phenotypes.
* Development of metabolically guided personalized approaches to the lifetime management of rare diseases
* Development of databases and computational tools to support metabolomics research.
* Development and application of technologies/products to support patients with rare diseases - particularly in low- and middle- income countries.
* Participation in the development of international best practices guidelines for diagnosis and treatment of rare diseases through comparative studies of public health policy.

This cutting edge research program is constantly expanded in various collaborations.