Skip to main content
Weiter zur Homepage der Europäischen Kommission (öffnet in neuem Fenster)
Deutsch de
CORDIS - Forschungsergebnisse der EU
CORDIS

Reprogramming inflammation via the DNA damage response-Metabolic axis control

Ziel

Chronic inflammation underlies autoimmune diseases, cancer, and aging. Yet current therapies fail to address underlying metabolic dysregulation of one-carbon metabolism (1C) or unresolved DNA damage triggering oxidative DNA damage response (OxDDR) that fuel persistent immune activation cycles. Here, we want to decode and target the one-carbon metabolism–oxidative DNA damage response (1C–OxDDR) axis, a critical but underexplored driver of persistent immune activation. We hypothesize that chronic DNA damage and rewired 1C metabolism enforce stable, disease-promoting immune phenotypes. To test this, we will map 1C–OxDDR circuits in patient tissues and aging models using multi-omics, spatial transcriptomics, and metabolic flux profiling to define signatures of disease initiation, progression, and therapy resistance. We will identify novel disease drivers and develop precision small molecules, leveraging our track record in developing first-in-class inhibitors to MTHFD1&2, OGG1 and MTH1 using an AI-integrated drug design. Furthermore, we will pioneer catalytic medicine through OGG1 amplizymes, introducing a new therapeutic paradigm that introduces novel enzymatic functions to proteins rather than inhibiting them. These strategies will be validated in advanced preclinical systems, including organoids and humanized models to reprogram immune dysfunction without broad immunosuppression. This high-risk/high-gain program builds on our success in synthetic lethality and PARP inhibitors, aiming to deliver a new precision medicine platform for inflammation-driven diseases. By integrating mechanistic insight with innovative medicinal chemistry, RECODE seeks to break the vicious cycle of chronic inflammation, opening therapeutic opportunities across auto-immunity, cancer, and aging, with impact comparable to our previously discovered paradigm-shifting cancer therapies.

Wissenschaftliches Gebiet (EuroSciVoc)

Dieses Projekt wurde noch nicht bei EuroSciVoc klassifiziert.
Schlagen Sie die Wissenschaftsbereiche vor, die Ihrer Einschätzung nach besonders relevant sind, und helfen Sie uns, unseren Klassifizierungsdienst zu verbessern.

Schlüsselbegriffe

Programm/Programme

Thema/Themen

Finanzierungsplan

HORIZON-ERC - HORIZON ERC Grants

Alle im Rahmen dieses Finanzierungsinstruments finanzierten Projekte anzeigen

Aufforderung zur Vorschlagseinreichung

(öffnet in neuem Fenster) ERC-2025-ADG

Alle im Rahmen dieser Aufforderung zur Einreichung von Vorschlägen finanzierten Projekte anzeigen

Gastgebende Einrichtung

KAROLINSKA INSTITUTET
Netto-EU-Beitrag
€ 2 500 000,00
Adresse
NOBELS VAG 5
171 77 STOCKHOLM
Schweden
Region
Östra Sverige Stockholm Stockholms län
Aktivitätstyp
Higher or Secondary Education Establishments
Links
Gesamtkosten
Keine Daten

Begünstigte (1)