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SP miRNA-Signaling Networks
Summary
Hypothesis:
We hypothesize that the trans-pathway regulation
via miRNAs creates synthetic interactions and is a
common mechanism of cells to keep phenotypes
under control, and that perturbations in key elements
of the regulated pathways could be exploited to
improve therapy
SP miRNA-Signaling Networks
Previous work
We previously combined a genome-wide
miRNA screening approach with a highthroughput quantitative proteomic
readout and network-based data
analysis to identify miRNAs regulating
EGFR signaling and cell cycle control,
and to uncover potential regulatory
patterns {Uhlmann, 2012 #3}. This
unraveled a network of modules being
co-regulated by miRNAs. We have
available the cell-lysates from the
original screen as well as a number of
validated antibodies and all required
technologies and instrumentation,
ready to quantify the abundance of key
proteins in other pathways
SP miRNA-Signaling Networks
Workpackages
WP/Aim 1: We will identify miRNAs that
interconnect signaling
pathways via genome-wide
screening, exploiting available
experimental resources.
WP/Aim 2: We will characterize these
miRNAs at the molecular level by
identifying target
genes/proteins, thus validating
links between individual signaling
pathways.
WP/Aim 3: We identify miRNAs impacting
cancer phenotypes, with special
emphasis on cell invasion.
WP/Aim 4: We will verify in vitro results in
mouse models (e.g. xenografts
overexpressing the respective
miRNAs and/or downregulating
the identified target mRNAs/inhibit
encoded proteins using drugs).
WP/Aim 5: We will establish clinical
significance using patient
samples as well as publicly
available data sets on miRNA and
mRNA gene
expression/regulation.
SP miRNA-Signaling Networks
Internal Networking
Aim 5
Aim 5
Aim 2
Aim 2
Aim 3
Aim 2
Aim 1,3
Aim 3
Aim 4