Description of the project
Training the next generation of researchers in resolution pharmacology
HARPNET is a Horizon Europe Marie Skłodowska-Curie Doctoral Network that prepares 15 doctoral candidates to transform how chronic inflammatory diseases are understood and treated.
A new therapeutic paradigm
Rather than simply suppressing inflammation, HARPNET investigates how endogenous resolution pathways can be activated to restore immune balance, promote tissue repair and prevent disease-associated organ damage.
Integrated research across disciplines
Using rheumatoid arthritis and its cardiovascular comorbidities as interconnected disease models, the network combines expertise in resolution biology, immunology, GPCR pharmacology, multi-omics, bioinformatics, medicinal chemistry and clinical translation.
Training researchers with lasting impact
Through 15 interconnected doctoral projects, HARPNET brings together academic, clinical and industrial partners to generate new biological insights, therapeutic candidates, biomarkers and computational tools while delivering an ambitious international and intersectoral training programme.
Background
When resolution fails, disease begins
Inflammation is an essential protective response to infection and injury. In health, it is followed by an active, tightly coordinated resolution phase that terminates inflammation, clears damaged cells and starts repair. When resolution fails, inflammation persists and drives chronic tissue damage, disability and disease progression.
Chronic inflammatory diseases rarely stay in one place. Rheumatoid arthritis is not restricted to the joints, patients face a higher risk of cardiovascular and metabolic complications. Yet research often studies single diseases and organs in isolation, and most treatments only inhibit inflammatory mediators: they control symptoms without consistently restoring tissue balance or removing long-term comorbidity risk.
Healthy
Inflammation rises, then actively resolves back to baseline.
Chronic
The approach
Resolution Pharmacology is a fundamentally different approach
It seeks to harness the body’s endogenous mechanisms for terminating inflammation and promoting repair. These mechanisms include specialised pro-resolving lipid mediators, peptides, receptors and signalling networks that reprogramme immune and stromal cells without broadly compromising host defence. The translation of this concept into medicines requires expertise that is rarely integrated within conventional doctoral programmes. HARPNET addresses this gap by combining fundamental resolution biology with pharmacology, disease modelling, multi-omics, artificial intelligence, medicinal chemistry, biomarker discovery and therapeutic development.
Research objectives
Four interconnected goals
Map defects in inflammation resolution
Identify shared and organ-specific alterations in pro-resolving pathways in rheumatoid arthritis and RA-associated cardiovascular disease, using clinical samples, experimental models and integrated multi-omics.
Define the underlying mechanisms
Determine how immune, stromal and vascular cells and molecular signalling networks interact to prevent or promote the resolution of chronic inflammation and tissue repair.
Develop next-generation therapeutics & tools
Design and evaluate new strategies for activating resolution pathways: GPCR agonists, specialised pro-resolving mediators, nanobodies, redox modulators and computationally designed compounds.
Enable clinical translation & precision medicine
Develop biomarkers, harmonised platforms, patient-stratification approaches and a shared RA–cardiovascular Resolution Atlas to support therapeutic development and future clinical studies.
Scientific programme
Fifteen projects, three work packages.
HARPNET’s scientific programme consists of 15 Individual Research Projects integrated across three scientific work packages. Data, technologies and biological models will be shared across projects through joint supervision, network activities and academic and industrial secondments.
Identifying dysregulated resolution pathways
WP1 will establish how inflammation-resolution mechanisms are altered across the joint, cardiovascular system and associated metabolic environments. Research will include:
- mapping pro-resolving pathways in acute and chronic arthritis;
- studying vascular and cardiac dysfunction associated with inflammatory arthritis;
- determining how specialised pro-resolving mediators influence joint and cardiovascular cells;
- analysing human epidemiological, genetic and multi-omic datasets;
- identifying genetic variants linked to mediator biosynthesis and disease susceptibility.
Defining molecular and cellular mechanisms
WP2 will investigate the signalling pathways and cellular interactions that control immune balance and tissue repair. Key research areas include:
- macrophage–fibroblast communication in the synovial environment;
- APP–TREM2 signalling in joint homeostasis;
- MCTR3 signalling in immune and stromal cells;
- canonical and atypical chemokine receptor networks;
- redox regulation and reversal of fibroblast inflammatory priming;
- specialised pro-resolving mediator control of vascular damage and tissue repair.
Developing therapeutic and translational solutions
WP3 will translate mechanistic discoveries into compounds, biomarkers and digital tools. Expected outputs include:
- the RA-ATLAS, integrating clinical and multi-omic information;
- computational tools for predicting drug mechanisms and patient responses;
- synthetic agonists and tool compounds targeting resolution pathways;
- Pro-resolving mediators in the regulation of haematopoiesis;
- lipid-mediator class-switching strategies;
- an artificial intelligence-supported framework for personalised therapeutic selection.
Integrated doctoral training
The research programme is supported by network-wide training in:
- Resolution Biology and Resolution Pharmacology;
- GPCR signalling and drug discovery;
- lipid mediator biology and mass spectrometry;
- spatial transcriptomics and multi-omics;
- bioinformatics, computational modelling and artificial intelligence;
- clinical translation and experimental medicine;
- intellectual property, entrepreneurship and regulatory science;
- scientific communication, stakeholder engagement and research leadership.
Doctoral Candidates will undertake international secondments, including exposure to the non-academic sector, and will be supported through joint supervision and an individual Career Development Plan.