Research Group

Pitzalis Group

Translational Rheumatology Lab

Pitzalis Group

Costantino Pitzalis

Clinical Group Leader

Our lab is committed to deciphering the cellular and molecular networks within target tissues that ignite, sustain, and shape the course of rheumatic autoimmune diseases. Bridging fundamental discovery with clinical insight, our research spans the entire therapeutic pathway - from the earliest molecular signals that anticipate treatment response to the complex mechanisms driving resistance. Through this integrative and translational approach, we strive to illuminate the underpinnings of disease variability and advance truly personalized preventive and therapeutic strategies for patients with rheumatic disorders.

The challenge

Rheumatic and systemic autoimmune diseases, such as rheumatoid arthritis, systemic lupus erythematosus, and Sjögren’s syndrome, remain a major challenge in modern medicine. These conditions arise from immune dysregulation, where the body attacks its own tissues, causing inflammation, pain, and organ damage. Despite therapeutic advances, many patients still experience unpredictable disease courses and incomplete responses to treatment. Each patient reflects a unique combination of molecular and cellular mechanisms shaping disease onset and progression. Dissecting such complexity requires integrated approaches linking research and clinical practice to develop precise, personalized strategies for diagnosis and treatment.

Main research area

Tissue-driven molecular stratification of autoimmune diseases (Rheumatoid Arthritis, Systemic Lupus Erythematosus and Sjogren syndrome)

Rheumatic and systemic autoimmune diseases are characterized by marked molecular and cellular heterogeneity that is not captured by current clinical classifications. By integrating minimally invasive tissue biopsies with multi-omics profiling, we define disease-relevant pathways directly within target tissues and identify molecular signatures associated with disease onset, progression, and therapeutic response. A central question is how tissue-specific molecular programs can improve patient stratification and guide precision medicine.

Mechanisms of treatment response and resistance in RA patients

Despite major therapeutic advances, a substantial proportion of patients experience incomplete or lost responses to treatment. Through longitudinal sampling and integrated molecular profiling, we investigate the mechanisms driving response, adaptation, and resistance, combining immune, stromal, and pharmacological data. A central question is which molecular and cellular determinants govern therapeutic response and how they can be translated into predictive biomarkers.

Immune-stromal interactions in chronic inflammation

Chronic inflammation is sustained by complex interactions between immune and tissue-resident cells within target tissues. We dissect these interactions using advanced sequencing and spatial technologies applied to patient-derived samples. A central question is how immune–stromal networks sustain disease activity and identify novel therapeutic targets.

Translational experimental medicine and clinical implementation

We are developing a tissue-driven experimental medicine framework that integrates molecular profiling into clinical decision-making and supports biomarker-guided strategies and innovative early-phase clinical trials. A central question is how to translate molecular insights into actionable interventions that improve patient outcomes.

Selected publications

Bruno D
Rheumatology (Oxford)
Synovial biopsy and tissue sampling in the management of RA
Nayar S
Nat Commun
Molecular and spatial analysis of tertiary lymphoid structures in Sjogren’s syndrome
MacDonald L
Immunity
Synovial tissue myeloid dendritic cell subsets exhibit distinct tissue-niche localization and function in health and rheumatoid arthritis
Nerviani A
Nat Commun
Axl and MerTK regulate synovial inflammation and are modulated by IL-6 inhibition in rheumatoid arthritis
Rivellese F
Lancet Rheumatol
Stratification of biological therapies by pathobiology in biologic-naive patients with rheumatoid arthritis (STRAP and STRAP-EU): two parallel, open-label, biopsy-driven, randomised trials
Colafrancesco S
Arthritis Rheumatol
Maladaptive Autophagy in the Pathogenesis of Autoimmune Epithelitis in Sjögren’s Syndrome
Alivernini S
Arthritis Rheumatol
Inclusion of Synovial Tissue-Derived Characteristics in a Nomogram for the Prediction of Treatment Response in Treatment-Naive Rheumatoid Arthritis Patients
Humby F
Lancet
Rituximab versus tocilizumab in anti-TNF inadequate responder patients with rheumatoid arthritis (R4RA): 16-week outcomes of a stratified, biopsy-driven, multicentre, open-label, phase 4 randomised controlled trial
Alivernini S
Nat Med
Distinct synovial tissue macrophage subsets regulate inflammation and remission in rheumatoid arthritis
Humby F
Ann Rheum Dis
Synovial cellular and molecular signatures stratify clinical response to csDMARD therapy and predict radiographic progression in early rheumatoid arthritis patients

Group members

Pitzalis Group
Dario Bruno

Clinician Scientist

Pitzalis Group
Serena Colafrancesco

Clinician Scientist

Pitzalis Group
Frazzei Giulia

Postdoc fellow

Pitzalis Group
Elisa Gremese

Associate professor, Humanitas University

Pitzalis Group
Michela Londero

Technician

Pitzalis Group
Giulia Pagani

Study Coordinator

Pitzalis Group
Costantino Pitzalis

Clinical Group Leader

Pitzalis Group
Valentina Pravatà

Technician

Pitzalis Group
Barbara Tolusso

Project Manager