# Global Measurements of Protein Folding Stability for Characterization of Aging and Disease

> **NIH NIH R01** · DUKE UNIVERSITY · 2022 · $302,725

## Abstract

ABSTRACT
 Genome- and proteome-based gene expression profiling studies have been widely used
over the past decade to characterize biological states including those associated with normal
biological process (e.g., aging) and with disease (e.g., cancer). While such differential gene
expression profiling studies can help identify the cellular pathways and physiological processes
associated with a biological state they often fail to produce a complete understanding of the
biological state because gene expression levels are not directly tied to protein function. This has
limited the number of useful protein biomarkers and therapeutic targets discovered from such
studies, and left gaps in our understanding of disease states. Proposed here is the development
and application of thermodynamic measurements of protein stability to characterize different
biological states including those associated with aging and cancer. Such thermodynamic
measurements of protein stability are expected to be more closely related to protein function
than are protein expression levels, and thus produce more useful protein biomarkers and
therapeutic targets of disease and generate a better understanding of the molecular basis of
disease.
 The proposed work will further develop and utilize three mass spectrometry-based
proteomics methods, termed SPROX, LiP and PP, to characterize the protein folding and
stability changes associated with a fundamental biological process, aging, and a disease,
colorectal cancer. The specific aims of this work are: (1) to interface SPROX and LiP with middle-
down proteomics methods to enable proteoform specific folding and stability measurments; (2)
to utilize the middle down SPROX and LiP workflows developed in (1) to make proteoform
specific thermodynamic stability measurements on mouse brain proteins derived from a mouse
model of aging; (3) to utilize the SPROX, LiP, and PP techniques to identify protein biomarker
with altered folding and stability in patient-derived colorectal cancer cell lines with different
sensitivities to oxaliplatin treatment; (4) to utilize the protein biomarkers discovered in (3) to
develop a clinically relevant assay for predicting oxaliplatin resistance/sensitivity in colorectal
cancer.

## Key facts

- **NIH application ID:** 10473697
- **Project number:** 5R01GM134716-04
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** Michael C Fitzgerald
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $302,725
- **Award type:** 5
- **Project period:** 2019-09-23 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10473697

## Citation

> US National Institutes of Health, RePORTER application 10473697, Global Measurements of Protein Folding Stability for Characterization of Aging and Disease (5R01GM134716-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10473697. Licensed CC0.

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