# Core B Proteomics & Biostatistics

> **NIH NIH P01** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2020 · $339,944

## Abstract

DESCRIPTION 
The aim of Core B is to provide innovative technologies to profile RAS mutation-specific effector signaling. 
RAS effector signaling is complex and involves RAS interaction with a multitude (>10) of functionally diverse 
downstream effectors. While our current understanding of RAS effector utilization is advanced, it is also far 
from complete. To date, four effector families have been implicated in driving RAS-dependent cancer initiation 
and growth. Each effector network includes protein kinases. There is also significant crosstalk between the 
effector networks. Furthermore, these networks are highly dynamic, with complex feed-forward and feedback 
mechanisms. Classically, RAS effector signaling is profiled by evaluation of the two canonical effector 
pathways, the RAF-MEK-ERK mitogen-activated protein kinase cascade and the PI3K-AKT-mTOR prosurvival 
signaling network, using the phosphorylated state of ERK and AKT as readouts. However, it is now clear that 
these analyses alone fail to provide an adequate determination of RAS effector signaling. Since a major goal 
of this Program Project is the determination of RAS mutant-specific effector signaling, unbiased kinome-wide 
analyses are needed to accomplish this goal. Core B provides two innovative proteomics-based experimental 
platforms to accomplish this. First, Multiplexed Inhibitor Beads (MIBs) and Mass Spectroscopy (MIB/MS) 
analyses provide kinome-wide profiling of dynamic changes in protein kinase activity. Our preliminary studies 
applying MIB/MS to characterize such changes upon KRAS suppression identified protein kinases not 
previously known as components of RAS effector signaling, demonstrating the potential for this platform to 
identify novel RAS effector signaling outputs. Second, Reverse Phase Protein Array (RPPA) analyses will 
profile RAS-dependent changes in protein phosphorylation and activation states in cancer cell signaling 
networks. Additionally, a recently developed innovative advance in RPPA enabling the profiling of the 
activation state of interacting proteins will also be applied. The types of data generated using each 
experimental platform are highly complementary. We expect that together they will define novel RAS mutation- 
specific effector signaling networks.

## Key facts

- **NIH application ID:** 9982066
- **Project number:** 5P01CA203657-05
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Lee M Graves
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $339,944
- **Award type:** 5
- **Project period:** — → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9982066

## Citation

> US National Institutes of Health, RePORTER application 9982066, Core B Proteomics & Biostatistics (5P01CA203657-05). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/9982066. Licensed CC0.

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