# Systematic discovery of neomorph protein-protein interactions in cancer for oncogenic pathway perturbation

> **NIH NIH U01** · EMORY UNIVERSITY · 2021 · $932,391

## Abstract

SUMMARY
The Molecular Interaction Center for Functional Genomics (MicFG) of Emory University proposes to understand
the functions of genomic mutations in cancer etiology through systematic interrogation of mutant allele-mediated
oncogenic protein-protein interactions (PPI) for target identification, validation, and perturbagen discovery across
cancer types, as a contributing member of the CTD2 Network. For synergistic effort, we have a team of
investigators and collaborators with complementary expertise in oncology, high throughput cancer biology and
chemical biology, cancer genomics, bioinformatics, computational structural biology and cancer validation
models. The wealth of available data for patient tumor-derived mutations offers unprecedented opportunities for
translational research to develop personalized therapies. It is these genomic alterations in each driver gene that
differentiate tumors from their normal counterparts. However, understanding how to leverage these genomic
changes at the mutated amino acid resolution for cancer target discovery and how to rapidly translate this
knowledge into genotype-directed cancer therapies for precision oncology remains a daunting and urgent
challenge. Our proposal aims to address this critical bottleneck with a team effort by directly focusing on cancer
mutation-created protein-protein interactions (neoPPI) for therapeutic discovery. To support this approach, we
have generated a comprehensive database representing the landscape of major somatic missense mutations in
TCGA pan-cancer datasets, and established a unique bioluminescence resonance energy transfer-based
quantitative high throughput wildtype/mutant differential screening (qHT-dS) platform. We hypothesize that
oncogenic neoPPIs can be rapidly uncovered by leveraging the cancer missense mutational landscape and
implementing a combined high throughput informatics and differential PPI screening platform for discovery and
validation of cancer targets for therapeutic discovery. To test this hypothesis, three specific aims are proposed:
(i) to identify and validate cancer mutation-created neoPPIs through differential screening with the qHT-dS
platform, (ii) to identify neoPPI disruptors as pathway perturbagens, and (iii) to develop and systematically apply
integrated informatics pipelines for neoPPI discovery. Our studies will lead to (i) creation of cancer mutation
expression vector libraries, large-scale PPI datasets, HTS neoPPI assays as a community resource, and
discovery of (ii) tumor-specific neoPPIs as promising cancer-specific targets, (iii) selected neo-PPI perturbagens
for oncogenic pathway disruption, and (iv) neoPPI informed potential biomarkers. Complementing the functional
annotation of mutant alleles in in vivo models by others, our systematic identification of cancer gene variant-
mediated neo-PPIs may reveal promising cancer-specific targets for genotype-directed therapeutic discovery.

## Key facts

- **NIH application ID:** 10210364
- **Project number:** 5U01CA217875-05
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** Haian Fu
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $932,391
- **Award type:** 5
- **Project period:** 2017-08-01 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10210364

## Citation

> US National Institutes of Health, RePORTER application 10210364, Systematic discovery of neomorph protein-protein interactions in cancer for oncogenic pathway perturbation (5U01CA217875-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10210364. Licensed CC0.

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