Project Details
Abstract
During the last granting period from 2007-2010, my laboratory developed RNAi and Telomerase
techniques to established several immortal G6PD cell lines which allowed us to first discover that
G6PD-deficient cells are more susceptible to viral infection. During the current granting period (2010-now),
my laboratory has continued our effort in searching for more evidence to support our hypothesis that G6PD is
a major player in regulating cellular redox homeostasis by maintaining proper NADPH to NADP+ ratio
which in turn plays a key role in the regulation of many cellular events. In the last couple of years, our
laboratory has applied nomic technologies to document that G6PD can affect protein expression and certain
subsequent metabolism such as alpha toxin detoxification. We have also found that upon encountering
exogenous oxidant, G6PD cells exhibit major alterations in global metabolome. Our biggest breakthrough
during this granting period is the establishment of a G6PD-deficient C. elegans animal model so that we can
extend our studies from cells to animal. More importantly, we have discovered that G6PD deficiency can
severely affect embryonic development in C. elegans. The current grant application details our research
plan (2014-2017) and emphasis that we will continue to delineate the biochemical and physiological roles of
G6PD in cells and animal model. The four Specific Aims for the current proposal are list below:
1. To investigate how does G6PD affect NOX in different cells upon oxidant challenge and the subsequent
signal transduction via the NOX pathway. (All will be completed in the 1st year)
1a. To prove the increased susceptibility of G6PD deficient cells to viral infection is due to the effects of
G6PD on redox homeostasis rendering cellular innate immunity abnormal.
1b.To investigate whether the delayed TNF- induced inflammatory responds is due to the effect of G6PD
on NOX.
1c. Using lipid-over loaded liver cells as an inflammation model to examine how does G6PD knockdown
affect cellular inflammatory responses.
2. To delineate how does G6PD knockdown affect protein expression upon exogenous oxidant challenge
using proteomic approach.
3. To dissect how does G6PD deficiency affect RBC metabolism upon exogenous oxidant challenge using
metabonomic approach.
4. To unravel the underlying mechanism of impaired embryonic development due to G6PD deficiency and to
test whether impaired lipid synthesis plays a role in this regard.
Upon completion of this proposed project, we will have a much better understanding of the underlying
mechanism for G6PD to regulate cellular redox homeostasis and the deleterious effects due to G6PD
deficiency, particularly the chronic effects.
Project IDs
Project ID:PC10308-0925
External Project ID:MOST103-2320-B182-026-MY2
External Project ID:MOST103-2320-B182-026-MY2
Status | Finished |
---|---|
Effective start/end date | 01/08/14 → 31/07/15 |
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