New Physiologic Roles of G6pd

In the past few years (from 2010 to present), our laboratory has established several G6PD deficient cell lines as well as nematode animal model to study the new roles of G6PD in biological systems. From these studies, our laboratory has confirmed the hypothesis that “G6PD is a regulator responsible for intracellular redox homeostasis, whereas G6PD deficiency alters redox balance and leads to many pathophysiologic effects”. Applying the cutting edge omics technologies, our laboratory has found that G6PD affects cellular protein expression (J Proteome Res. 12:3434-48, 2013) and global metabolite levels (Free Radical Bio Med. 54:71-84, 2013) through proteomic (iTRAQ) and metabolomics (LC-MS) techniques, respectively. Moreover, our recent reports indicate that the reduction of G6PD status has impacted cellular inflammatory response (J Inflamm-Lond. 12:34, 2015) and immune response against viral infection (Viruses-Basel. 7:6689-706, 2015). A major breakthrough of this granting period is the establishment of global metabolites of G6PD-deficient erythrocytes challenged by exogenous oxidant. Such information provides comprehensive information for accessing G6PD metabolic status and from the medical technology aspect, can provide novel biomarker such as ophthalmate to assess oxidative stress in clinical samples (Antioxid Redox Sign. 22:744-59, 2015; IF＞7.4). In the current proposal, we have formulated four specific aims as an extension from our previous G6PD studies: 1. To investigate the signaling pathways of how altered G6PD activity affects TNF-α-induced inflammatory and anti-viral responses as well as the mechanistic interaction between G6PD and NADPH oxidase (NOX). 2. To determine whether the activation of inflammasome is influenced by G6PD deficiency. 3. To study the mechanism of how G6PD status impacts embryonic development by using nematode (C. elegans) and zebrafish (D. rerio) animal models. 4. To delineate the correlation between G6PD deficiency and infectious diseases by analyzing National Health Insurance Research Database (NHIRD) By completing these specific aims, we will greatly understand the underlying mechanism of how G6PD affects cells, organisms and clinical presentations through redox homeostasis.

Project ID:PC10507-0206
External Project ID:MOST105-2320-B182-031-MY2