Browsing by Author "Birerdinc, Aybike"

Now showing 1 - 2 of 2
  • Thumbnail Image
    Item
    Knowledge-Based Identification of Soluble Biomarkers: Hepatic Fibrosis in NAFLD as an Example
    (Public Library of Science, 2013-02-06) Page, Sandra; Birerdinc, Aybike; Estep, Michael; Stepanova, Maria; Afendy, Arian; Petricoin, Emanuel; Younossi, Zobair; Chandhoke, Vikas; Baranova, Ancha
    The discovery of biomarkers is often performed using high-throughput proteomics-based platforms and is limited to the molecules recognized by a given set of purified and validated antigens or antibodies. Knowledge-based, or systems biology, approaches that involve the analysis of integrated data, predominantly molecular pathways and networks may infer quantitative changes in the levels of biomolecules not included by the given assay from the levels of the analytes profiled. In this study we attempted to use a knowledge-based approach to predict biomarkers reflecting the changes in underlying protein phosphorylation events using Nonalcoholic Fatty Liver Disease (NAFLD) as a model. Two soluble biomarkers, CCL-2 and FasL, were inferred in silico as relevant to NAFLD pathogenesis. Predictive performance of these biomarkers was studied using serum samples collected from patients with histologically proven NAFLD. Serum levels of both molecules, in combination with clinical and demographic data, were predictive of hepatic fibrosis in a cohort of NAFLD patients. Our study suggests that (1) NASH-specific disruption of the kinase-driven signaling cascades in visceral adipose tissue lead to detectable changes in the levels of soluble molecules released into the bloodstream, and (2) biomarkers discovered in silico could contribute to predictive models for non-malignant chronic diseases.
  • Thumbnail Image
    Item
    Role of KCNRG in B-CELL Chronic Lymphocytic Leukemia
    (2008-12-22T21:05:08Z) Birerdinc, Aybike; Birerdinc, Aybike
    B-cell chronic lymphocyte leukemia (B-CLL) accounts for approximately 30% of all leukemias in the Western world and has so far been treated with variable success. The newly characterized KCNRG gene has been mapped to chromosome 13q14.3. KCNRG is thought to be a tumor suppressor gene involved in the development of B-cell chronic lymphocytic leukemia due to its significant homology to the tetramerization (T1) domain of the voltage-gated potassium channels (Kv channels) and an ability to suppress growth-stimulating Kv currents. Since point mutations of KCNRG have not been found in B-CLL samples, a novel approach for its study based on a haploinsufficiency model was suggested. The aim of this study is to determine whether the KCNRG gene functions as growth suppressor in tumor cell lines and to elucidate a putative role for the loss of this gene in the development and the progression of B-CLL. Overexpression studies of KCNRG were performed in an attempted to determine the involvement of KCNRG in apoptosis, differentiation, and invasion of cultured human tumor cells, and the effects of overexpression of KCNRG on gene expression and proteomics profiles were quantified.