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> *Dissertation Defense Announcement
> 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.
>
> ###