# p53-mediated metabolic regulation in tumor suppression

> **NIH NIH R35** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2024 · $923,400

## Abstract

Project Summary
 Inactivation of the p53 tumor suppressor is a pivotal event in the formation of most human
cancers. p53 acts as a transcription factor to modulate various types of cellular processes to
suppress cancer development. Although the classic activities of p53 including cell-cycle arrest,
senescence and apoptosis serve as critical barriers to cancer development, accumulating
evidence suggests that other unconventional mechanisms such as metabolic regulation are also
critically involved in suppressing tumor growth. Nevertheless, despite the fact that the role of the
p53 pathway in tumor suppression is indisputable, it remains a daunting task how to target this
pathway for cancer therapy. The main issue is whether activation of p53 function in vivo leads to
significant tumor regression without causing serious toxicity in normal tissues. Cancer cells rewire
cellular metabolism to meet the energetic and substrate demands of tumor development, but this
rewiring also creates metabolic vulnerabilities specific for cancer cells. By taking advantage of
these metabolic vulnerabilities, our preliminary studies showed that specific activation of the tumor
suppression function of p53 through certain metabolic targets can be effective in suppressing
tumor growth but apparently does not cause severe harm to normal tissues. The central
objective of the proposed research plan is to comprehensively define p53-mediated metabolic
regulation program that is required for its tumor suppression as a mean to identify new
targets/pathways for therapy. Toward this end, our research program will be based on two
complementary lines of research aiming to the further dissection of: 1) p53-mediated metabolic
pathways required for its tumor suppression; 2) the novel ferroptosis pathway regulated by p53
and the effects in both normal and cancer cells. We expect that the research program described
above will identify specific targets to suppress tumor growth but have minimal or at least
manageable toxicity in normal tissues.

## Key facts

- **NIH application ID:** 10898749
- **Project number:** 5R35CA253059-04
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Wei Gu
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $923,400
- **Award type:** 5
- **Project period:** 2021-09-01 → 2028-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10898749

## Citation

> US National Institutes of Health, RePORTER application 10898749, p53-mediated metabolic regulation in tumor suppression (5R35CA253059-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10898749. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*