# Metabolic adaptations in melanoma brain metastasis

> **NIH NIH R21** · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · 2024 · $198,103

## Abstract

ABSTRACT
 Melanoma brain metastasis (MBM) is a deadly, poorly understood consequence of melanoma for which
patients need improved treatment options. In integrating proteomics and transcriptomics data from independent
patient cohorts, CNDP1 was identified as a commonly upregulated gene in MBM. CNDP1, or carnosine
dipeptidase-1, cleaves carnosine into its component amino acids L-histidine and ß-alanine. Carnosine is
abundant in muscle, liver, and in the brain, where it exerts neuroprotective effects5. While carnosine itself is
thought to exert anti-tumorigenic effects, the role of CNDP1 in cancer remains vastly unknown.
 To probe the functional role of CNDP1 in MBM, we assessed the effects of CNDP1 depletion in MBM in
vitro and in vivo. Constitutive CNDP1 silencing reduced melanoma cells’ ability to colonize the brain parenchyma,
and inducible suppression impaired growth of established MBMs in preclinical mouse models. Mechanistically,
our preliminary studies suggest that, in addition to carnosine cleavage, CNDP1 may regulate cellular amino acid
pools, aminoacyl-tRNA availability and protein translation, particularly of mitochondrial proteins. Our findings
suggest the possibility that higher CNDP1 levels allow melanoma cells to withstand high carnosine levels and
oxidative stress during brain metastasis.
 This proposal aims to: 1) solidify the value and specificity of CNDP1 as a novel MBM target, using
preclinical models and genetic and pharmacological approaches, and 2) dissect its mechanism(s) of action.

## Key facts

- **NIH application ID:** 10785565
- **Project number:** 1R21CA286244-01
- **Recipient organization:** NEW YORK UNIVERSITY SCHOOL OF MEDICINE
- **Principal Investigator:** Eva Hernando
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $198,103
- **Award type:** 1
- **Project period:** 2024-01-01 → 2025-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10785565

## Citation

> US National Institutes of Health, RePORTER application 10785565, Metabolic adaptations in melanoma brain metastasis (1R21CA286244-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10785565. Licensed CC0.

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