# Systems Analysis of Stress-adapted Cancer Organelles (SASCO) Center

> **NIH NIH U54** · UNIVERSITY OF VIRGINIA · 2024 · $2,018,318

## Abstract

PROJECT SUMMARY/ABSTRACT
Oncogene activation is modulated by normal subcellular compartments that execute specialized functions
related to hallmark cancer phenotypes. These organelles must adapt to oncogenic stress in order for tumors
to initiate and progress, but there is little to no systems-level understanding of how such adaptations occur and
what vulnerabilities might be created. The Systems Analysis of Stress-adapted Cancer Organelles (SASCO)
Center at the University of Virginia will address this challenge by mechanistic modeling of organellar processes
that iterates with quantitative experiments in disease-relevant cell cultures and primary tumors. The working
SASCO Center hypothesis is that organelle-specific adaptation to oncogenic stress occurs through a few
critical bottlenecks, which become identifiable once the relevant signaling, metabolic, and transport pathways
have been properly integrated. The Center brings together 14 investigators with primary and collaborative
track records in cancer biology, systems biology, genetically engineered mouse models of cancer, and clinical
practice. Three Research Projects and one Shared Research Core will pursue a common research strategy,
which leverages mechanistic models to test competing alternative hypotheses about how organelles adapt to
stresses from proximal oncogenes that drive specific types of cancer. The Projects are organized
hierarchically as organelle stresses downstream of proliferation-inducing oncogenes. Project 1 will examine
the chromosome passenger complex and its regulated phase separation during metaphase as an organelle
that senses and repairs spindle defects to suppress breast cancer aneuploidy driven by mitotic transcription
factors. Project 2 will evaluate the metabolic consequences of chronic mitochondrial fragmentation caused by
mutant KRAS in primary colorectal cancers and secondary liver metastases. Project 3 will investigate localized
signal-transduction rebalancing as a mechanism for alleviating plasma-membrane stress caused by EGFR
amplification in glioblastoma. All Research Projects will rely on the High-Content Imaging & Analysis Core to
obtain iterative multichannel immunofluorescence data with organelle-level resolution and quantification. The
SASCO Outreach Core amplifies ongoing programs at the University of Virginia to provide summer research
experiences for undergraduates and faculty scholars from historically underrepresented backgrounds as well
as introductory systems biology modeling materials for clinicians across the Commonwealth of Virginia. The
SASCO Center will thus create a national headquarters for subcellular cancer systems biology within the
broader Cancer Systems Biology Consortium.

## Key facts

- **NIH application ID:** 10903892
- **Project number:** 5U54CA274499-03
- **Recipient organization:** UNIVERSITY OF VIRGINIA
- **Principal Investigator:** Kevin A Janes
- **Activity code:** U54 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $2,018,318
- **Award type:** 5
- **Project period:** 2022-09-12 → 2027-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10903892

## Citation

> US National Institutes of Health, RePORTER application 10903892, Systems Analysis of Stress-adapted Cancer Organelles (SASCO) Center (5U54CA274499-03). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10903892. Licensed CC0.

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