# Proteogenomic Studies aimed at understanding ovarian tumor responses to agents targeting the DNA damage response and translating this knowledge into clinical benefit

> **NIH NIH U01** · FRED HUTCHINSON CANCER RESEARCH CENTER · 2020 · $440,000

## Abstract

ABSTRACT
We will provide the Alzheimer’s disease (AD) community with a novel assay resource based on advanced
methodology that enables precise, highly specific, standardizable, multiplex quantification of the innate immunity-
complement protein network in AD brain tissues. The innate immune response and its ties to inflammation are
important to the pathophysiology of AD (see Pubmed IDs: 31654430, 30740661, 32046242, 31427930,
31702392, 31907273). For example, in AD, a neuroinflammatory response is associated with fibrillar plaques,
and elevated levels of inflammatory proteins are detectable in AD brains. Innate immune response proteins (e.g.
complement proteins) are associated with amyloid plaques in human AD brains, and the complement cascade
can be directly activated in vitro by fibrillar Ab and neurofibrillary tangles. As stated in a recent review (PMID:
31907273), “Quantitative studies on the balance between activators and inhibitors of complement in injured brain
and the influence of the complotype on progression of AD could be useful in designing personalized therapies
in the future. Although much remains to be clarified, targeting specific effector pathways of complement is
justified now as a potential therapeutic strategy for this debilitating neurodegenerative disease.” Regulation of
the immune system is the result of interplay amongst many 100s of proteins, and it will no doubt be important to
quantify these regulatory networks in order to deliver new immunotherapies effectively (e.g., personalized
medicine”) and to develop new immunotherapies (many of these proteins may themselves be viable therapeutic
targets, or modulated in response to effective immune therapies). Furthermore, conventional protein
quantification approaches (e.g. immunoassays) typically target one analyte at a time, which is not adequate for
studying the behavior of a complex and robust signaling network such as innate immunity. We will develop
multiplex assays to quantify proteins in the innate immune network, using a NextGen protein quantification
platform based on a targeted form of mass spectrometry called multiple reaction monitoring (MRM). All assay
protocols and validation data will be made publicly available as a novel resource to the community via the
established, open-source NCI Assay Portal (assays.cancer.gov). We believe that this work is likely to stimulate
additional work leading to progress on AD by providing the AD community with a novel assay resource based
on advanced methodology that enables precise, highly specific, standardizable, multiplex quantification of the
inflammation / innate immunity protein network in AD brains.

## Key facts

- **NIH application ID:** 10122633
- **Project number:** 3U01CA214114-04S1
- **Recipient organization:** FRED HUTCHINSON CANCER RESEARCH CENTER
- **Principal Investigator:** Michael Birrer
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $440,000
- **Award type:** 3
- **Project period:** 2017-06-01 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10122633

## Citation

> US National Institutes of Health, RePORTER application 10122633, Proteogenomic Studies aimed at understanding ovarian tumor responses to agents targeting the DNA damage response and translating this knowledge into clinical benefit (3U01CA214114-04S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10122633. Licensed CC0.

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