# Systems Metabolic Approach for Multi-scale Pancreatic Cancer Phenotyping

> **NIH NIH R37** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2024 · $622,984

## Abstract

ABSTRACT
Pancreatic cancer is an aggressive, painful malignancy with a 5 year survival rate of less than 5% and median
survival of about 4 to 24 months. The overall lack of success of chemotherapy treatments underscores, at least
in part, the incomplete understanding of how pancreatic adenocarcinoma (PDAC) grows and invades local and
distant tissues. There continues to be novel discoveries with respect to genetic mutations that predispose
individuals to developing PDAC, histopathological features with prognostic implications, and clinical imaging
(functional metabolic and anatomic, e.g. PET/CT) that define clinical stage and guide treatment options.
However, overall, each diagnostic modality in large part, remain independent of one another. Consequently there
is a need to assess and integrate measurements from the cell, tissue, and organ levels with multiple imaging
modalities and to evaluate the concordance across different types of measurements and spatial scales in order
to characterize the “molecular omic-type to clinical phenotype” relationship. Linking measurements from these
different disciplines, radiology, pathology, and high-throughput molecular measurements, will help to establish
more definitive phenotypes of PDAC that are consistent across multiple spatial scales.
Recently many of the changes in PDAC have evolved around changes in the metabolic aspects of the tumor
microenvironment and the interactions between tumor cells and the surrounding stromal cells, thus we focus on
identifying metabolically driven/related phenotypes. We hypothesize that characterizing the PDAC
microenvironment tumor-stroma interface at the cell and tissue levels will enable assessment of glycolytic and
inflammatory characteristics of tumors in relation to specific histological tumor characteristics (e.g. perineural
invasion and lymphovascular invasion) and this will lead to 1) a non-invasive imaging test to identify PDAC
phenotypes and 2) new potential cellular targets for treatment. A data-driven systems biology approach using
transcription-signaling-metabolic network reconstructions and constraint-based modeling will be used as the tie
that binds a wide array of disparate data, including cellular microscopy, 3D preserved architecture tissue imaging,
and PET/CT imaging in order to define a non-invasive functional, metabolic phenotyping measurement of PDAC
that corresponds to cellular phenotypes. The constraint-based genome scale integrative modeling framework
allows the simultaneous analysis of multiple types of data in interacting populations of cells. Additionally through
the acquisition of multi-parametric cross- sectional imaging, it will be possible to evaluate whether or not
metabolic changes on the cellular level have any manifestations on the tissue level. The environment, team, and
resources assembled at UCLA are poised in a unique position to carry out these studies and achieve success
in developing a non-invasive imaging approach for phenotyping P...

## Key facts

- **NIH application ID:** 10946197
- **Project number:** 1R37CA292781-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** Neema Jamshidi
- **Activity code:** R37 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $622,984
- **Award type:** 1
- **Project period:** 2024-08-01 → 2029-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10946197

## Citation

> US National Institutes of Health, RePORTER application 10946197, Systems Metabolic Approach for Multi-scale Pancreatic Cancer Phenotyping (1R37CA292781-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10946197. Licensed CC0.

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