ANNOUNCEMENT

NOBEL PRIZE 2026

This year's laureates, their fields, and the discoveries that earned them the prize.Live nowSee the winners
Moonbase
← Back to Awards
NIHNATIONAL CANCER INSTITUTE

Metabolic adaptations in melanoma brain metastasis

Completed
Institution
NEW YORK UNIVERSITY SCHOOL OF MEDICINE, NY
Principal investigator
Eva Hernando
Funding
$238K
Duration
2024–2025
Open portfolio

Moonbase score

Still being scored

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.

LOADING MOONBASE SCORE

NATIONAL CANCER INSTITUTER21ZCA1-SRB-P(O2)Sbrainmelanomametastasisaminobrain parenchymamelanoma cellsbrain metastasismelanoma patients

Questions for NEW YORK UNIVERSITY SCHOOL OF MEDICINE

Answered by the team behind this research.

No questions yet. Sign in to ask the first one

Related grants

Same researchers, same institution, same topic, scored first.