# Core 2: Human Specimen and Organic Core (HSO Core)

> **NIH NIH P01** · SALK INSTITUTE FOR BIOLOGICAL STUDIES · 2023 · $293,113

## Abstract

PROJECT SUMMARY – Core 2: Human Specimen and Organoid Core
Patients diagnosed with pancreatic ductal adenocarcinoma (PDA) often fail to respond to therapeutic intervention
or rapidly develop resistance to treatment. To study mechanisms of therapeutic resistance, the assembled P01
research team will utilize a large and representative cohort of PDA patient-derived three-dimensional organoid
models (PDOs). Organoids accurately recapitulate the genomic, transcriptomic, and phenotypic characteristics
of human PDA and enable predictive profiling of drug response in a heterogenous patient-cohort. The Human
Specimen and Organoid Core (HSO Core) will facilitate the elucidation of mechanisms of resistance in
collaboration with each Research Project. The HSO Core will test numerous novel therapeutic combinations to
determine effective and synergistic strategies. The Core will provide a powerful patient-derived organotypic
tumor slice platform for ex vivo mechanistic studies. In addition, the HSO Core will generate organoid co-cultures
with key stromal cells and will develop organoids from genetically engineered mouse (GEM) models that develop
spontaneous PDA. The overall goal of the HSO Core is to support each Project in the discovery and validation
of effective therapeutic strategies to overcome treatment resistance. To accomplish this, the HSO Core has three
Aims. In Aim 1, The Core will provide methodology expertise and valuable PDO models tailored to each
individual Project. Novel therapeutic combinations that include drugs such as Entinostat (Project 1) and ULK1/2
inhibitors (Project 3) will be profiled using a pharmacotyping assay that takes advantage of the Core’s
heterogenous cohort of organoids. Combinations will be evaluated and synergies mathematically defined.
Existing DNA/RNA-sequencing datasets will be leveraged to discover predictive signatures of drug sensitivity
and resistance. In Aim 2, the Core will provide access to an organotypic living tumor slice model that preserves
the neoplastic and stromal cellular compartments of PDA. Methodologies developed by the HSO Core allow for
ex vivo culture up to 7 days, enabling the perturbation and characterization of cell to cell signaling networks.
Further, the Core will develop co-culture systems that incorporate epithelial organoids, fibroblasts, and immune
cells in collaboration with Projects 2. Finally in Aim 3, the Core will collaborate with the Mouse Models Core to
generate mouse-derived organoids from previously unavailable GEM models and develop organoid resources
to facilitate the workflow of the Research Projects and Cores.

## Key facts

- **NIH application ID:** 10629068
- **Project number:** 1P01CA265762-01A1
- **Recipient organization:** SALK INSTITUTE FOR BIOLOGICAL STUDIES
- **Principal Investigator:** Herve Tiriac
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $293,113
- **Award type:** 1
- **Project period:** 2023-07-06 → 2028-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10629068

## Citation

> US National Institutes of Health, RePORTER application 10629068, Core 2: Human Specimen and Organic Core (HSO Core) (1P01CA265762-01A1). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10629068. Licensed CC0.

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