# Core B: Metabolomics/Genomics Core

> **NIH NIH P01** · UNIVERSITY OF PENNSYLVANIA · 2020 · $130,955

## Abstract

Summary
The central tenet of this Program Project is that the Integrated Stress Response (ISR) plays a pivotal role
in mediating MYC-dependent and hypoxia-dependent tumor progression through its capacity to engage
and regulate key pathways involved in circadian, metabolic and immune functions thereby facilitating
tumor cell survival and growth.
The combination of non-cell autonomous stresses (hypoxia, and nutrient deprivation) coupled with the
increased bioenergetics demands of a rapidly proliferating cell imposed by MYC transformation
necessitate rewiring of metabolism towards a higher glycolytic rate (Warburg effect) as well as a more
reducing environment to combat increased ROS produced by the still ongoing respiration. Preliminary
data form all 3 projects impinge upon processes which affect metabolic and redox status: MYC activation,
circadian clock dysregulation and T cell activation have all been implicated in changes in central carbon
metabolism. Therefore, a Core which provides “turn-key” services in the analysis of such metabolites will
be crucial for the efficient and rapid advancement of key findings with cellular as well as animal models.
At the same time, the fact that Myc and ATF4 (key components in all 3 projects) are transcription factors
exerting their activity through extensive networks and partners, necessitates the analysis of gene
expression profiles, including mRNAs and miRNAs. Finally, project 2 will rely heavily on the performance
of ChiP-Seq experiments for Myc and ATF4 in different settings, generating data-rich outcomes which
require expert bioinformatics tools to parse important data. Under Aim 1, the Core will analyze levels of
metabolites, including products of glycolysis, amino acids and ATP levels from tumor and normal tissues
and cells using NMR and mass spectrometry. Under Aim 2, the Core will analyze levels of gene
expression including mRNA, miRNA and non-coding RNA from normal and tumor tissues and cells, and
perform bioinformatics analysis, ontology analysis and data visualization.
 Moreover, the integration of the Metabolomics and Genomics (Bioinformatics) efforts under a single
Core and coordination of our activities would enable direct comparisons between genomic and
metabolomic data as additional level of validation of specific hypotheses (e.g., microRNA X represses
synthesis of enzyme Y production which should result in changes in levels of metabolite Z). Successful
implementation of these Aims will serve as a catalyst for increased operational efficiency and integration
of ideas and concepts among the three main Program Projects.

## Key facts

- **NIH application ID:** 10017917
- **Project number:** 5P01CA165997-07
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Aalim M Weljie
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $130,955
- **Award type:** 5
- **Project period:** 2013-09-18 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10017917

## Citation

> US National Institutes of Health, RePORTER application 10017917, Core B: Metabolomics/Genomics Core (5P01CA165997-07). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10017917. Licensed CC0.

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