> Dissertation Defense Announcement
> To:  The George Mason University Community
>
> Candidate: David L. Armistead
> Program:    PhD Biosciences
>
> Date:   Thursday June 7, 2012
> Time:   11:00 a.m.
> Place:  George Mason University
>             Research Hall, Room #161
>             Fairfax Campus <http://www.gmu.edu/resources/visitors/>
>  
> Dissertation Director/Committee Chair: Dr. Ancha Baranova
> Committee members: Dr. Zobair Younossi, Dr. Vikas Chandhoke, Dr. 
> Patrick Gillevet
> Title: "Differential Expression of microRNAs in the Visceral Adipose 
> of Patients with NASH, Pericellular Fibrosis and Type II Diabetes"
>
> 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:*
>
> Non-alcoholic steatohepatitis (NASH) is the progressive form of 
> non-alcoholic fatty liver disease (NAFLD). NASH is one of the least 
> understood metabolic consequences of obesity. The dysregulation of 
> visceral adipose derived signaling molecules, including adipokines, 
> oxidative stressors and cytokines is associated with the progression 
> of NAFLD. MicroRNAs (miRNAs) represent a new class of 
> post-transcriptional regulators of gene expression. These non-coding 
> single stranded molecules are predicted to regulate a third of all 
> human genes as they interact with certain recognition motifs found 
> within the 3' un-translated region (UTR) of protein coding mRNAs. 
> These interactions ultimately down regulate gene expression through 
> mechanisms of translational repression, mRNA destabilization 
> --mediated repression or direct mRNA degradation. In this study we 
> profiled 664 mature miRNAs derived from the visceral white adipose 
> tissue (WAT) of morbidly obese patients with NASH and non-NASH NAFLD. 
> A global down-regulation of 84 mature miRNAs (Fold Change > -1.7 and 
> P- < 0.05) was observed in patients with NASH when compared to 
> non-NASH NAFLD controls. A total of 54 adipose derived mature miRNAs 
> (Fold Change > -1.7 and P- < 0.05) were differentially expressed in 
> NASH patients with pericellular fibrosis when compared to non-NASH 
> NAFLD controls. Additionally, 6 primary transcript miRNA (pri-miRNA) 
> assays were designed and tested for locus specific NASH related 
> transcription. Of these, a single primary miRNA transcript, miR-7-1 ( 
> Fold Change > 1.7 and P -- < 0.01) was found to be up-regulated in 
> NASH vs. Non-NASH NAFLD. Lastly, a systems biology analysis of NASH 
> related miRNAs was performed to better elucidate orchestrated 
> communication between visceral WAT and the liver, as well as the 
> hepatic consequences of obesity related adipose remodeling. The 
> results from our ontology enrichment analysis clearly associate a 
> global downregulation of adipose specific miRNAs with hepatocellular 
> carcinoma, liver neoplasms as well as chronic liver disease. 
> Furthermore, our systems biology analysis revealed that NASH related 
> adipose derived miRNA expression is associated with the dysegulation 
> of the peroxisome proliferator-activated receptor (PPAR) pathway, 
> inflammation pathways and may be associated with adiponectin reduced 
> AMP-activated protein kinase (AMPK) signaling in the liver.   This is 
> the first study to our knowledge which links the deregulation of WAT 
> miRNA expression and the progression of NAFLD.
>
>  ###
>