SPOKE 1
Holistic Nosology and Omics Sciences
Mapping the omics landscape from the molecular environment to the clinical setting, in order to identify, classify, and refine the phenotypes of multifactorial diseases.
Spoke Leader and Expertise
Università degli Studi di Roma Tor Vergata
The University of Rome Tor Vergata is recognized at both national and international levels for its expertise in precision medicine applied to genomics, epigenetics, and the molecular biology of complex diseases. Within HEAL Italia, Spoke 1 is responsible for redefining nosology—that is, the classification of diseases—moving beyond an approach based solely on symptoms to integrate genetic, molecular, metabolic, and environmental information.
Partner
- Istituto Superiore di Sanità
- IRCCS Neuromed – Istituto Neurologico Mediterraneo
- Sapienza Università di Roma
- Fondazione Toscana Life Sciences
- Alma Mater Studiorum Università di Bologna
- Università degli Studi di Cagliari
- Università degli Studi di Foggia
- Università degli Studi di Modena e Reggio Emilia
- Università Politecnica delle Marche
- Università degli Studi di Verona
Scientific Coordinator
Prof. Eleonora Candi
Mission
The mission of the thematic network (Spoke 1) is to understand the underlying causes of complex and multifactorial diseases by identifying the biological mechanisms that determine why one person develops a disease while another does not, and why the same disease can present with different clinical forms.
Spoke 1 adopts a holistic nosology approach, which considers disease as the result of the interaction between genetic background, epigenetic regulation (mechanisms that control the activation or deactivation of genes), metabolism, the immune system, and environmental exposures. This approach makes it possible to move beyond traditional “reactive” medicine and to guide prevention and treatment toward targeted and personalized interventions.
Objectives
- Identify predictive and prognostic biomarkers for major chronic diseases.
- Improve patient stratification by distinguishing subgroups with different risks and responses.
- Provide solid biological foundations for advanced diagnostics and predictive models.
- Identify new therapeutic targets and support the repurposing of existing drugs.
- Supply data and knowledge to support the other Spokes within the HEAL Italia value chain.
Activities
The activities of Spoke 1 are primarily carried out through the analysis of population cohorts, that is, groups of individuals followed over time with the systematic collection of clinical, biological, and environmental data. These include large longitudinal studies that have been active in Italy for years, enabling the observation of the transition from health to disease and the identification of early risk factors.
The Spoke uses multi-omics technologies, that is, approaches that simultaneously analyze different biological levels:
- Genomics and exome analysis, to identify common and rare genetic variants
- Epigenomics, to study the effect of the environment on gene expression
- Transcriptomics, to analyze which genes are active under specific conditions
- Proteomics and metabolomics, to measure proteins and metabolites as dynamic indicators of health and disease status
These data are integrated with clinical information, lifestyle factors, and environmental exposures, thanks to the support of the digital infrastructures developed in the other Spokes. In parallel, the Spoke works on experimental cellular and animal models to causally validate the role of specific biological pathways identified in population studies.
A key area of activity concerns the study of the so-called “common soil,” the shared biological ground that links seemingly different conditions, such as cardiovascular, metabolic, oncological, and neurodegenerative diseases. Understanding these common mechanisms makes it possible to identify cross-cutting prevention and intervention strategies.
Areas of Work
Population mapping: DNA sequencing and exome mapping aimed at identifying pathogenic genetic variants
- Precision medicine: the “common soil” hypothesis and the Moli-sani / RoCAV studies
- Genomics, phenomics, and biomarkers
- Metabolome mapping from murine models to Moli-sani sub-cohorts and the development of new therapeutic targets
Transcriptomics: the “common soil” hypothesis and personalized medicine
- Omics biomarker analysis for the stratification of obesity and metabolic complications
- Multi-omics approach for high-impact diseases: personalization of treatments and therapeutic response
- Serine metabolism and ncRNA-mediated epigenetic regulation
Proteomic and metabolic analysis: study of dynamic interactomes
- Impact of microbial metabolites on diseases: from translational models to clinical practice
- Protein degradation mechanisms in physiological and pathological conditions
- Autophagy, cell cycle regulation, and pathological correlations
Metabolic alterations and metabolome mapping
- Long-chain fatty acid enzymes and lipid metabolism
- Imaging and calcium signaling ($Ca^{2+}$) as indicators of metabolic adaptations
- Interaction between genetics and environment in metabolic and pathological dysregulation
Projects Funded through Cascade Calls
MOCISAP
Modulation of Intracellular Calcium Signaling as a New Precision Anticancer Strategy
The project aims to counteract the uncontrolled proliferation and resistance to apoptosis typical of cancer by focusing on the regulatory role of calcium (Ca²⁺) and the mitochondrial permeability transition pore (mPTP). Since Ca²⁺ governs both programmed cell death—by activating the mPTP—and tumor growth through oscillations that influence the cell cycle, the research will analyze these mechanisms in high-mortality or hard-to-treat cancers, such as colon, lung, glioblastoma, and mesothelioma, in order to identify new therapeutic strategies and genetic biomarkers. The integration of calcium-modulating drugs with conventional treatments will enhance clinical efficacy, providing new tools for diagnosis, prognosis, and the development of targeted molecular therapies.
PROMINENT
Personalised Rna-Oriented MedIcINE in Italy Novel Therapeutics
The project aims to develop non-invasive, sustainable, and evidence-based diagnostic pathways to optimize the prediction, early detection, and monitoring of monogenic, cardiovascular, metabolic, and oncological diseases. Through the application of precision medicine and the validation of the “common soil” hypothesis, the research integrates data from the Moli-sani cohort and other population studies with advanced analyses in genomics, phenomics, and biomarkers. By mapping the metabolome from murine models to human clinical subgroups, the initiative aims not only to make diagnostics more accessible and accurate, but also to identify new innovative therapeutic targets for timely and personalized clinical management.
