Presentazione
Presentazione del Corso di Dottorato in Medicina Traslazionale
Obiettivi formativi
La missione del corso di dottorato è formare ricercatori capaci di sviluppare progetti di ricerca che colmino la distanza fra le attività di laboratorio e le scienze cliniche, facilitando il processo traslazionale in entrambe le direzioni.
Obiettivi:
1. apprendere a studiare le strutture biologiche nei diversi livelli di organizzazione, le loro modificazioni fisiologiche e patologiche nel quadro delle interazioni fra persona e ambiente esplorando interventi diagnostici e terapeutici, facilitando il loro approdo alla pratica clinica;
2. apprendere un percorso di ricerca scientifica traslazionale volto a favorire l’intersezione fra le scoperte biologiche e clinico-comportamentali e la pratica preventiva, terapeutica e riabilitativa, al fine di migliorare salute e stili di vita, anche in considerazione della tendenza mondiale all’aumento dell’attesa di vita;
3. acquisire una solida base nelle discipline metodologiche necessarie per la formulazione corretta di ipotesi sperimentali, la definizione di disegni sperimentali e l’interpretazione critica dei risultati;
4. promuovere la comunicazione fra la ricerca biologica e quella clinico-comportamentale specificamente per quanto attiene i processi che sottendono il movimento e l’attività fisica nelle aree della prevenzione, del benessere psico-fisico, delle prestazioni sportive e professionali, in condizioni di salute, malattia e disabilità, in una prospettiva unitaria;
5. comprendere le implicazioni etiche della ricerca biologica e clinica.
Il corso di dottorato è erogato interamente in lingua inglese.
Programmi di ricerca
Programmi di ricerca
Programmi di ricerca
39° Ciclo - Bando di Concorso 2023/2024
• Molecular and cellular mechanisms of pathogenesis of vascular calcification in uremia. Vascular calcification (VC) is a major feature of the increased cardiovascular risk in end stage renal disease (ESRD) patients. The aim of this project is to study the effect of uremic toxins on vascular smooth muscle and endothelial cells and to setup a new in vitro model of co-colture, to better understand the pathogenesis of VC in uremia (Cozzolino)
• Role of sphingolipids in the mechanism of repair of damaged myelin, with focus on multiple sclerosis (Prinetti)
• Morphological and metrical assessment of the skeleton: study of the biological variability in clinical, surgical and anthropological contexts (Gibelli)
• Nanotechnological approaches for diagnosis, treatment and management of cancer (Mazzucchelli)
• Cellular and molecular mechanisms underlying Kleesftar syndrome (Gervasini)
• V-ATPase at the crossroad of epigenetics and bioenergetics in glioma stem cells (Vaira)
• Development of preclinical models of acute lung injury for the optimization of the ventilatory and extracoporeal support (Mauri-Zanella)
• BAL-EV (bronchoalveolar lavage fluid-extracellular vesicles) signaling in the lung microenvironment of lung transplanted patients (Vaira)
• Study of infectivity and severity of SARS-CoV-2 and other respiratory viruses based on isolated variants (Delbue)
• Establishment of new in vitro models to study the West nile virus-host interaction and seroepidemiologic studies on emerging arbovirus infections (Delbue)
• Molecular mechanisms of host–parasite interactions in cutaneous Leishmaniasis: new in vitro 2D-3D models to unveil the role of macrophages, keratinocytes, and endothelial cells in the establishment of infection at the site of inoculum (Basilico-D’Alessandro)
• Immunomodulatory activity of vector-borne, protozoa parasites (Malaria & Leishmania) and their products on macrophages, microglia, and endothelial cells from different anatomical origins: implication for the pathogenesis and establishment of chronic infections (D’Alessandro-Basilico)
• Innate immunity in malaria-leishmaniasis co-infection: role of the Pattern Recognition Receptors (PRR) in macrophages activation and dendritic cells maturation (Basilico-Parapini)
• Drug discovery for vector borne, poverty-related, emerging parasitic diseases, malaria and leishmaniasis: identification of novel potential antiparasitic compounds and their mechanisms of action to overcome the problem of resistance (Parapini-Basilico)
• Pathogenic implications of co-infections. In vitro models to study immunological, molecular and epigenetic determinants (Clerici)
• Identification of new vaccine strategies for the generation of effective and lasting humoral and cell-mediated responses (Trabattoni)
• Characterization of molecular mechanisms involved in antigen presentation pathway responsible for antiviral immune response (Biasin)
• Effects of microplastics on the immune system and on inflammatory processes (Fenizia)
• Aggressive pituitary tumors: correlation between clinical and molecular characteristics (Mantovani)
• Immunophenotyping of peripheral and target tissue-resident lymphocytes in Graves’ Disease and Orbitopathy with predictive, prognostic and therapeutic purposes (Mantovani-Muller)
• Combining whole exome and RNA sequencing to identify genetic and molecular pathways in neuromuscular disorders and to characterize patient cohorts for gene therapy (SEQMD) (Ronchi)
• In-vitro and in-vivo development of a mRNA-based therapeutics for primary mitochondrial encephalohepatopathies (Ronchi)
• Biomechanics and bioenergetics of human locomotion in simulated hypogravity (Pavei)
• In vivo human studies of exercise-stimulated metabolism to elicit anti-inflammatory and immunomodulatory responses in dysmetabolic conditions. In particular, it wil be covered: incremental exercise testing in normal weight, overweight/obese subjects, and athletes - measurements, clinical indications, and metabolic determinants related to energy metabolism (Codella)
• Role of extracellular vesicles (EVs) in modulating pathological processes (Caretti)
• Role of the (sphingo)lipid metabolism in the pathological fibrotic process (Caretti)
• (Sphingo)lipid dysmetabolism and primary hepatic cancer (Caretti)
• Novel syndromic alterations associated with the glycosphingolipid dismetabolism (Caretti-Trinchera)
• Characterization of the effect extracellular matrix components, tumor microenvironment and 3D arrangement on carcinoma progression (Gagliano)
• Study of collagen turnover and expression of genes and proteins involved in extracellular matrix remodeling in connective tissue in physiological and pathological conditions, and after pharmacological treatment (Gagliano)
• Study of metabolism alterations in cardiomyophaties : identification of predictive and prognostic markers and therapeutic targets (Signorelli)
• Study of energy metabolism in Parkinson's neurodegeneration and of the molecular and metabolic effects of the electrostimulation therapy in Parkinson's disease (Signorelli)
• Role of the small airways in the physiopathology of pulmonary diseases, with particular reference to the effects of small airways cyclic opening and closing in patients with chronic obstructive pulmonary disease (COPD) and in animal models (Pecchiari)
• Identification and functional validation of new candidate genes in patients with rare endocrine diseases by combined NGS analyses (WES, targeted, WGS): in vitro and /or in vivo studies (Fugazzola-Colombo-Cirello-Cangiano-Muzza)
• Network Physiology (NP) is an emerging field of computational physiology that allows to study the cardiovascular and cerebrovascular regulatory systems and their dynamical interactions. The project will evaluate associations between the functioning of physiological control mechanisms, as assessed via typical NP methods before major cardiac surgery, and the development of postoperative cardiovascular and cerebrovascular adverse events (Porta)
• An impairment of the cardiac neural control during physical exercise and recovery phase can expose the subject to the risk of arrhythmic events. The project will use advanced time series analysis techniques for the indirect assessment of the cardiac neural control during maximal physical exercise and the return to baseline situation (Porta-Esposti)
• Cerebrovascular autoregulation is a fundamental mechanism for maintaining adequate cerebral perfusion in the presence of blood pressure changes. The autonomic nervous system plays an important role in the regulation of vascular resistances. The project will use advanced signal processing techniques to characterize the interaction between the autonomic nervous system and cerebrovascular autoregulation in physiological conditions and in critical situations (Porta)
• Biomarkers associated with the diagnosis of Schizophrenia and Mood Disorders: epigenetic, inflammatory and hormonal factors involved in the etiology and outcome of these psychiatric conditions (Buoli)
• Sphingolipid metabolism and signaling as a therapeutic target in tumor cells. The research project aims to study sphingolipid-mediated signal transduction mechanisms in physio-pathological processes with the aim of identifying targets for the development of innovative and effective therapies against tumors. In particular, the metabolism and the functional properties of specific sphingoid mediators will be investigated in the tumorigenicity of tumor and /or cancer stem cells (Giussani)
• The project plans to study platelet activation in patients thrombocytopenia associated to different immune diseases with hemorrhagic or thrombotic phenotype, evaluating the modulation of therapies. Platelet activation will be evaluated "ex vivo" and "in vitro" through flowcytometry and using a microfluidic platform. This system simulates the conditions of the blood flow and allows to evaluate platelet thromboformation by varying analytical conditions (Podda)
• Dissetting the molecular mechanism that links loss of lysosomal function with the onset of Parkinson's disease and development of new therapeutic strategies (Aureli)
• Lipid-based therapeutic strategies to optimize the effectiveness of innovative drugs to rescue mutated CFTR (Aureli)
• Identification and evaluation of the genetic mechanisms underlying liver disease development to develop precision medicine approaches (Valenti)
• Morphofunctional tuning of the body barriers: nutraceutical applications (Donetti)
• Three-dimensional analysis of human movement in health, disease and sports (Sforza)
• Three-dimensional analysis of human head morphology in health and disease (Sforza)
• Development of cellular and molecular therapeutic approaches for neurological diseases (Corti)
• Etiopathogenetic study and translational medicine research applied to neuromuscular and neurodegenerative diseases (Comi)
• Hypertension and cardiac fibrosis focus on cellular crosstalk and sphingolipid signaling on heart tissue estracts from hypertensive Emilin 1 knockout mice, by monitoring protein and sphingolipid composition in heart tissue extracts and cardiomyocytes. Objectives will be reached by untargeted LC-MS/MS analysis for protein and sphingolipids followed by validation. Advanced bioinformatics tools will be utilized for data interpretation obtained by high-throughput technologies. The project will provide better insight into mechanisms contributing to cardiac fibrosis (Gelfi)
• Comprehensive analysis of the determinants of the metabolic cost of running, via 3D motion capture, dynamometry, EMG, ultrasound measurements, in order to assess and explain the role of elastic energy stored and released by the muscle-tendon unit, in causing its independence from the progression speed (Minetti)
• Autonomic nervous system assessment to optimize training in elite athletes and to optimize exercise prescription for cardio‐metabolic and cancer treatment/prevention (Lucini)
• lifestyle (focusing mainly on physical exercise) as sustainable tool for individual, environment and society, fostering wellbeing and reducing cardiometabolic risk factors (Lucini)
• Hereditary angioedema due to C1-inhibitor deficiency (HAE) is a rare and potentially fatal autosomal dominant disease characterised by localized edema of the subcutaneous and submucosal tissue.
It can be considered the paradigm of Paroxysmal Permeability Diseases (PPDs), pathological conditions characterized by sudden, recurrent, but reversible increase of endothelial permeability without inflammatory, degenerative or ischemic injury. Considering the central role of endothelium in PPD the project will address the interplay between endothelial cells and C1INH in the pathophysiology of HAE (Caccia)
• Analysis of AMPK role in preventing atrial electrical remodeling associated wIth age-dependent arrhythmias (Baruscotti)
• This research program will provide basic knowledge of neuroimaging, omic, neurotransmitter and neurocognitive bases of the major psychiatric illnesses, such as psychotic, mood and anxiety spectrum disorders, with particular regards to brain connectivity and prefronto-limbic neuropsychological, omic, and neuromodulatory dimensions. Examples will be provided on how brain imaging, neurophysiological, omic, and neuropsychological multimodal multisource measures need to be analysed and integrated, and how they can be translated into clinical knowledge for assessment of pathophysiology, diagnosis, prognosis, and treatment response of those major psychiatric disorders (Brambilla)
• Study of the gastrointestinal tract as a pathogenic site of HIV infection. We aim to asses the mucosal barrier, local immunity and the microbiome during HIV infection (Tincati)
• Immunepathogenesis of PACS (Post-Acute Covid-19 syndrome). Wer aim to investigate T and B-cell immunity in subjects with PACS (Tincati)
• New "omics" approaches for mitochondrial disorders (Ghezzi)
• Thrombotic thrombocytopenic purpura (TTP) is a disease characterized by organ damage caused by the formation of clots in the microcirculation, especially in the cerebral circulation. Recent studies have shown that patients with TTP are at risk of developing cerebrovascular events during clinical remission. This may be the result of endothelial dysfunction that occurs during the acute event and that may continue in some patients during clinical remission. In this study, we propose to estimate the prevalence of cerebralsmall vessel disease through the identification of typical neuroradiological features, and to evaluate its association with new biomarkers of neuronal, astrocytic, and microcirculatory damage, in order to identify predictive biomarkers of an increased risk of cerebrovascular events (Payvandi)
• Predictive and complementary biomarkers in HR+/ HER2- breast cancer. The project will combine histology, immunohistochemistry and next-generation sequencing techniques on tissue and liquid biopsy samples to identify clinically relevant subgroup of patients (Fusco)
• Identification and study of clinicopathological and molecular biomarkers predictive of response or resistance to PARP inhibitors therapies in solid tumors. This project, which will use molecular biology and digital pathology techniques, will be carried out within the Oncology Genetics Unit at the Division of Pathology at the European Institute of Oncology (Guerini Rocco)
• Integrated approach for the characterisation of bacterial virulence and resistance factors, host immunity and microbiota in severe infections in critically ill patients: identification of possible targets for intervention. The project includes the characterisation by sequencing of the bacterial genome with the identification of virulence and resistance factors, the study of innate and adaptive immunity and the analysis of the microbiota (intestinal and respiratory) (Gori)
• Translational research on biological material from COVID-19 patients has the objective to understand disease mechanisms and identify therapeutic targets to address future epidemics. Aims of the research are to investigate the immunological, genetic, and epigenetic patients’ features with acute SARS-CoV-2 infection and the molecular characteristics of the virus, and to explore which disease mechanisms and host factors are associated with COVID-19 severity. The project has the final objective to improve disease management, identify possible therapeutic and vaccine-mediated immune targets (Gori)
• Understanding pathogenetic mechanisms in polymicrobial biofilms (Borghi)
• Microbiota-gut-brain axis in neurodevelopmental disorders (Borghi-Vignoli)
• Molecular and phylogenetic approaches for studying pathogens with a high social and health burden (Bianchi)
• Cellular senescence and neurodegeneration (Massa)
• Molecular mechanisms in Cornelia de Lange syndrome (Massa)
• 3D models for studying neurodevelopment (Massa-Gervasini)
• Identification of prognostic biomarkers of adaptive immunity in inflammatory bowel diseases (Caprioli)
• Role of nutrition in the modulation of the intestinal micorbiota and of the mucosal immune system in inflammatory bowel diseases (Caprioli)
• Nanotechnological approaches for diagnosis, treatment and management of cancer (Mazzucchelli)
• Patient-derived organoid of breast cancer: development, characterization and application in tumor biology studies (Mazzucchelli)
• Identification and evaluation of the genetic mechanisms underlying liver disease development to develop precision medicine approaches (Valenti)
• From exosomes to mini-guts: unveiling the pathogenesis of Crohn’s disease to personalize therapy (Nebuloni)