>> *Dissertation Defense Reminder
>> To:  The George Mason University Community*
>>
>> *Candidate: Sandra J. Page
>> Program:    PhD Biosciences
>> *
>> *Date:   Monday August 29, 2011
>> Time:   2:00 p.m. 
>> Place:  George Mason University
>> ** 	     Discovery Hall Auditorium
>> 	     Prince William campus <http://www.gmu.edu/resources/visitors/findex.html>
>>   
>> *Dissertation Chair: Dr. Ancha Baranova
>> Committee members: Dr. Emanuel Petricoin III, Dr. James D. Willett, Dr. Gregory Foster
>> *
>> Title: **"Novel Biomarkers for Non-Alcoholic Fatty Liver Disease
>> 	  and Associated Symptoms"
>>
>> *The dissertation is on reserve in the Johnson Center Library, Fairfax campus.
>> The doctoral project will not be read at the meeting, but should be read in advance. 
>> /**/
>> *All members of the George Mason University community are invited to attend.*
>>
>>
>> *ABSTRACT: *
>>   
>>
>> Obesity is on the rise in populations across the world, and 
>> represents a major health concern. It is a component of Metabolic 
>> Syndrome, a collection of risk factors that predispose to diabetes 
>> and cardiovascular disease. Metabolic Syndrome is often accompanied 
>> by non-alcoholic fatty liver disease (NAFLD), a spectrum of liver 
>> disease ranging from simple steatosis, to non-alcoholic 
>> steatohepatitis (NASH) and liver fibrosis. Currently, the gold 
>> standard for NASH and liver fibrosis diagnostics is liver biopsy; 
>> thus, a non-invasive procedure for detecting and staging NAFLD is 
>> greatly needed. The dissertation work to be presented involved 
>> evaluating various kinds of serum-based, soluble molecules as 
>> biomarkers of NASH, NASH-related fibrosis, or its associated 
>> symptoms. In the first study, a biomarker panel for NASH and 
>> NASH-related fibrosis was developed by screening several proteins 
>> previously associated with liver disease but never tested in 
>> combination; these included hormones derived from adipose tissue 
>> (adipokines) and proteins involved in fibrogenesis and cell death. 
>> The resulting panel outperformed previously reported biomarkers of 
>> NASH and hepatic fibrosis, and it is anticipated that subsequent 
>> testing of this panel on larger populations of NAFLD patients will 
>> ultimately support its use in clinical settings.
>>
>>             A second study was conducted with the goal of discovering 
>> novel, as-of-yet untested biomarkers of NASH and NASH-related 
>> fibrosis that may be tied to the deregulation of cell signaling 
>> pathways in adipose tissue. A previous study using a phosphoproteomic 
>> approach showed that several kinase-driven pathways were deregulated 
>> in the adipose tissue of patients with NASH and NASH-related 
>> fibrosis. Enrichment analysis on this data set showed that these 
>> pathways were linked to the regulation of cell functions by insulin. 
>> A subsequent pathway analysis was then conducted to identify a set of 
>> secreted, soluble proteins associated with these pathways. From this 
>> analysis two promising candidates were selected based on extensive 
>> literature searches; these were the chemokine CCL-2/MCP-1, and 
>> soluble Fas ligand. These candidates were then tested on a small 
>> cohort of patients with NASH and NASH-related fibrosis to determine 
>> if they had the potential to be diagnostically predictive, and it was 
>> discovered that both worked reasonably well as biomarkers of 
>> fibrosis. Consequently, these molecules may be released at abnormal 
>> levels by adipose tissue in patients with NAFLD and may in turn play 
>> a role in fibrogenesis associated with NASH; they would therefore be 
>> good candidates to test in future development of biomarker panels for 
>> NASH-related fibrosis.
>>
>>             A third study was undertaken to evaluate the association 
>> between levels of various soluble molecules and fatigue in patients 
>> with NAFLD or hepatitis C. Specifically, we correlated self-reported 
>> assessments of fatigue dissecting this condition into fatigue 
>> associated with physical activity (peripheral fatigue) or more global 
>> lack of energy and motivation (central fatigue) with measures of 
>> inflammation, or with abnormalities of glucose and lipid metabolism. 
>> The study demonstrated that a substantial majority of patients with 
>> chronic liver disease report significant peripheral fatigue. This 
>> type of fatigue was linked to elevated serum levels of IL-6 and IL-8, 
>> linking it to an inflammatory component, which is not the case for 
>> central fatigue.
>>
>> ###
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