Chronic Disease Laboratory
Dr. Baranova's Laboratory Website
Potential 2012 Aspiring Scientists Summer Internship Projects
Mentors: Dr. Ancha Baranova, Dr. Michael Estep and Dr. Aybike Birerdinc
* This laboratory is located at Inova Fairfax Hospital
* This ASSIP opportunity is only available for undergraduate students
1. Brown Adipose Tissue (BAT) Mitochondria Study
Morbid obesity has been linked to a variety of severe, progressively degenerating conditions such as NASH, NAFLD, reproductive and cardiovascular disorders. There has been some novel discoveries indicating that white adipose tissue (WAT) may not be the only player in this complex metabolic condition. The discovery of metabolically active brown fat (BAT) is gaining the attention of researchers in numerous disciplines, including liver disease. The emerging data suggests that BAT not only plays a role in adult body weight homeostasis, but may also contribute to the regulatory mechanisms of obesity. Brown adipose tissue (BAT) works to control body temperature in hibernating animals and newborn infants and until recently was believed to decrease with age in adults. One of the major limitations of gene expression studies in the determination of the presence of BAT is that by its very definition, the BAT related genes must be active. Recent research has suggested however, that BAT cells can remain “dormant” under certain conditions, therefore the detection of total BAT content can not be achieved by gene expression analysis. One of the distinguishing factors of BAT is the large number of mitochondria found in this type of cell. Indeed, these mitochondria are what gives BAT its “brown” appearance. In this study we propose to quantify both mitochondria specific DNA and total DNA in order to obtain a ratio indicative of the total BAT cells in NASH and non-NASH subjects, irrespective of the “activation” status of the BAT cells. Briefly, we will extract total DNA and total RNA from visceral adipose tissue of patients with varying degrees of NAFLD and we will assess the ratio of mitochondrial specific genes versus total DNA as an indicator of the presence of BAT cells. We will also assess the expression levels of BAT specific genes as well as genes involved in BAT differentiation.
2. Vitamin D levels in NAFLD and NASH
Vitamin D is known to be a steroid hormone involved in the intestinal absorption of calcium and the regulation of calcium homeostasis. Recent evidence suggest that Vitamin D deficiency may have a potential role in the inflammatory processes and there is a an ever increasing body of literature indicating that low vitamin D levels may play an instrumental role in the development of both hypertension and metabolic syndrome (MS) Pertinent to NAFLD and NASH, a significant inverse relationship between serum vitamin D levels and unexplained elevation in ALT was observed in NHANES III cohort recently. Consequently, the examination of vitamin D levels in patients with NASH with various degrees of liver involvement, may lead to a better understanding of the relationship between liver disease and vitamin D. In addition, if vitamin D is found to be intimately involved in the pathogenesis and progression of NASH, it may prove to be a reliable and non-invasive biomarker of severity of the disease and its propensity for progression. We will assess the serum levels of Vitamin D, PTH, M30 and calcium and correlate data with the liver health status of morbidly obese NAFLD patients.
3. MMP9 levels in serum of CHC patients
Previous studies shown a differential expression of MMP9, a major fibrosis related metalloproteinase, after exposure to infectious and inflammatory stimuli. The development of fibrosis in the course of C-HC is not a well predicted event and currently clinicians do not have any biomarkers to indicate which patients are at risk to develop fibrosis and which are not. We will use ELISA’s to measure the serum levels of MMP9, in addition to MMP9 gene expression in PBMC’s of patients with Chronic Hepatitis C (CHC) and correlate these with the occurrence of fibrosis. Statistical and predictive models including clinical and demographic data will also be constructed.
4. Cytokine Imbalance and Depression
Recent studies have linked major depression with increased Th1 activation and inflammatory response. In fact numerous studies have shown a strong involvement of the Th1/Th2 imbalance in the cellular responses of the brain during both psychological stress and with psychiatric disorders. Interestingly, obesity and the related plethora of metabolic conditions are also known to be pro-inflammatory in nature and may push this Th1/Th2 balance towards an increased inflammatory state. These data necessitate a closer examination of the levels of Th1 class and Th2 class of cytokines in obese/ NAFLD patients with depression as the existence of these co-morbidities may in fact involve a pre-existing imbalance in the host Th1/Th2 levels rendering certain patients vulnerable to this condition. We will assess the status of Th1 and Th2 class of cytokines in obese/ NAFLD patients with and without clinical depression to assess the relationship between inflammatory cytokines and depression. The cytokines assessed will include: IL-1B, IL-7, IL-8, GM-CSF, MCP-1, MIP-1B, IL2, IL4, IL5, IL6, IL10, IL12, IL13, IL17A, IFNγ, TNFα, G-CSF and TGFβ1.