Dipartimento di Medicina e Chirurgia
Università degli Studi di Perugia

• Patologia e Clinica dell'Arteriosclerosi e dell'Invecchiamento

Studio del metabolismo lipidico e glucidico, dei fattori di rischio vascolare e della risposta immuno-infiammatoria nella fisiopatologia del danno vascolare aterosclerotico. 

Identificazione di biomarcatori di aterosclerosi e valutazione dei processi fisiopatologici delle malattie età relate. Interazione tra processi infettivi a diversa etiologia e turbe metaboliche e della omeostasi vascolare arteriosa.

Basi fisiopatologiche del metabolismo glucidico e lipidico e dell'azione di fattori di rischio per la malattia aterosclerotica, sindrome metabolica, steatosi epatica.

Individuazione ed uso di marcatori molecolari, bioumorali e funzionali di aterosclerosi e delle principali patologie età-relate.

Studi pre-clinici e clinici per la caratterizzazione e la modulazione di biomarcatori di invecchiamento e patologie età-relate, in particolare senescenza cellulare, alterazioni telomeriche, infiammazione, alterazioni epigenetiche, alterata comunicazione intercellulare. Individuazione di marcatori innovativi basata su approcci di metabolomica.

Immunità innata e tolleranza immunitaria, ruolo nelle malattie cardio-metaboliche ed infiammatorie nell'invecchiamento, nelle patologie età-relate, nella sindrome da fragilità.

Caratterizzazione fisiopatologica e clinica della fragilità, fisica e cognitiva, e delle principali sindromi geriatriche, in particolare delirium, cadute e fratture da fragilità.

Studi clinici per l'identificazione dei determinanti biologici, fisiopatologici e clinico-assistenziali di esito funzionale e di salute nel paziente anziano in fase acuta, in particolare quello ortogeriatrico.

Studi clinici per l'individuazione di strategie di medicina di precisione.

Studi di fattibilità e di efficacia di procedure e nuovi modelli organizzativo-assistenziali.

Studio delle interazioni ospite-parassita, con particolare riferimento alla eziopatogenesi, diagnosi con tecnologie innovative (incluse quelle di Next Generation Sequencing) delle infezioni tempo dipendenti, da microorganismi multiresistenti e altri patogeni di rilevanza epidemica o pandemica.

Gli obiettivi del Curriculum sono la formazione di ricercatori autonomi altamente specializzati in settori specifici di una ricerca biomedica che si rivolga ai soggetti con complessità clinica ed ai processi biologici alla base delle patologie cardiovascolari, dell’invecchiamento e delle patologie infettive.

COLLABORAZIONI INTERNAZIONALI: Karolinska Institute, Stockholm, Sweden Department of Neurobiology, Care Sciences and Society, (Prof. Eric Westman, Prof. Silvia Maioli, Prof. Francesca Mangialasche, Prof. Bengt Winblad), Aging Research Center-ARC (Prof. Laura Fratiglioni), Center for Alzheimer Research (CAR) (Prof. Daniel Ferreira Padilla, Prof. Dorota Religa); Brain Health Institute, Stockholm, Sweden (Prof. Miia Kivipelto); Institute of Clinical Medicine, Neurology, University of Eastern Finland, Kuopio, Finland (Prof. Alina Solomon); Department of Public Health and Welfare, Finnish Institute for Health and Welfare, Helsinki, Finland (Prof. Tiia Ngandu); Department of Neurology, Medical University of Vienna, Austria (Prof. Elizabeth Stögmann); FH Joanneum, Graz, Austria (Prof. Sten Hanke) University Medical Center, UMC, Amsterdam, Netherlands (Prof. Wiesje van der Flier); Université de Lille, Inserm, CHU Lille, Institut Pasteur de Lille, France (Prof. Jean-Charles Lambert); Human Nutrition Unit, Biochemistry and Biotechnology Department, University Hospital of Sant Joan de Reus, IISPV, Rovira i Virgili University, Reus, Spain (Prof. Jordi Salas Salvadò); Translational Health Sciences, Bristol Medical School, University of Bristol, United Kingdom (Prof. Patrick Kehoe); Ageing Clinical Research, Department II of Internal Medicine and Center for Molecular Medicine, University Hospital Cologne, University of Cologne, Germany (Prof. Maria Cristina Polidori); Department of Medicine, Academy of Applied Medical and Social Sciences—AMiSNS: Akademia Medycznych I Spolecznych Nauk Stosowanych, Elbląg, Poland (Prof. Luigi Marano); Electrical and Computer Engineering Department, ESDA Lab, Professor University of Peloponnese, Greece (Prof. Nikolaos Voros); Department of Orthopaedics, University Hospital of Patras, Greece (Prof. Elias Panagiotopoulos); Department of Clinical Gerontology, Robert-Bosch-Hospital, Stuttgart, Germany (Prof. Clemens Becker);  Department of Geriatrics and Geriatric Rehabilitation, Lausanne University Hospital, Lausanne, Switzerland (Prof. Patrizia D'Amelio); Pôle Maladies du Vieillissement, Gérontologie Et Soins Palliatifs, Université de Lorraine, Nancy, France (Prof. Athanase Benetos); Alzheimer's Center at Temple, Lewis Katz School of Medicine, Temple University, Philadelphia, USA (Prof. Domenico Praticò); Department of Chemistry and Sanders-Brown Center on Aging, University of Kentucky, Lexington, USA (Prof. Allan D. Butterfield); Longevity Institute and Davis School of Gerontology, University of Southern California, Los Angeles, USA (Prof. Valter Longo); Longitudinal Studies Section, Translational Gerontology Branch, National Institute on Aging, Baltimore, USA (Prof. Luigi Ferrucci); Center for Cell Signaling, Department of Microbiology, Biochemistry, and Molecular Genetics, New Jersey Medical School, Rutgers University, Newark, USA (Prof. Utz Herbig).

Division of Cardiovascular Medicine, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden (Prof. Per Eriksson, Prof. Bruna Gigante, Prof. Rona J Strawbridge); Division of Medicine and Department of Clinical Sciences, Danderyd Hospital, Karolinska Institutet, Stockholm, Sweden (Prof. Louis Ziegler); Institute of Health and Wellbeing, University of Glasgow, UK (Prof. Rona J Strawbridge); Health Data Research, Clarice Pears Building, Glasgow, UK (Prof. Rona J Strawbridge); Cardiovascular Genetics, Institute Cardiovascular Science, University College London, UK (Prof. Steve E. Humphries); Lipidology and Cardiovascular Prevention Unit, Department of Nutrition, Sorbonne Université, INSERM UMR1166, APHP, Hôpital Pitié-Salpètriêre, Paris, France (Prof. Antonio Gallo); Unités de Prévention Cardiovasculaire, Assistance Publique-Hôpitaux de Paris, Service Endocrinologie-Métabolisme, Groupe Hospitalier Pitié-Salpétrière, Paris, France (Prof. Philippe Giral); Pitié-Salpetrière Hospital and Sorbonne University, Cardio metabolic Institute, Paris, France (Prof. Eric Bruckert); Department of Medicine, University Medical Center Groningen, Groningen & Isala Clinics Zwolle, Groningen, the Netherlands (Prof. Andries J Smith); Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio Campus, Kuopio, Finland (Prof. Sudir Kurl); Kuopio Research Institute of Exercise Medicine, Kuopio, Finland (Prof. Kai Savonen); Department of Clinical Physiology and Nuclear Medicine, Science Service Center, Kuopio University Hospital, Kuopio, Finland (Prof. Kai Savonen). Department of Medical Sciences, Uppsala University, Uppsala Science Park, Uppsala, Sweden (Prof. Lars Lind); Department of Cardiology, Danderyd University Hospital, Stockholm, Sweden (Prof. Bruna Gigante); Department of Preventive Cardiology and Lipidology, Medical University of Lodz (MUL), Poland (Prof. Macjei Banach); Liverpool Centre for Cardiovascular Science, Liverpool, UK (Prof. Peter E. Penson); Department of Nutritional Sciences and Dietetics, International Hellenic University, Thessaloniki, Greece (Prof. Niki Katsiki); The Johns Hopkins Ciccarone Center for the Prevention of Heart Disease, Baltimore, MD, USA; Preventive Cardiology, CGH Medical Center, Sterling, USA (Prof. Dimitri P Mikhailidis, Prof. Peter Toth); Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran (Prof. Amirhossein Sahebkar); Department of Internal Medicine, University Hospital Centre Zagreb, School of Medicine University of Zagreb, Zagreb, Croatia (Prof. Zeljko Reiner); Clinica de Cardiologie, Institutul de Boli Cardiovasculare Timisoara, Timisoara, Romania (Prof. Dan Gaita).

COLLABORAZIONI IN NETWORK NAZIONALI ED INTERNAZIONALI: REPOSI (REgistro dei pazienti per lo studio delle polipatologie e POliterapie in reparti della rete Simi); AEQUI (Aged European population QUality of life in Infectious diseases); International Lipid Expert Panel (ILEP); Piattaforma IMPROVE; European Atherosclerosis Society Familial Hypercholesterolaemia Studies Collaboration; Lipid Clinics Network Group; Rete LIPIGEN Study Group; Rete LIPIGEN Paediatric Group; Centro Cardiologico Monzino, Milano; Italian COVID Group; Intensive Care, Infectious Diseases COVID-19 Study Group; ADA Group; TSUNAMI Study group.

• Neuroscienze

Il Curriculum di Neuroscienze è incentrato sullo studio dei meccanismi patogenetici e di biomarcatori innovativi in diverse malattie neurologiche, quali le malattie neurodegenerative, neuroinfiammatorie, le cefalee e l’epilessia. Gli studenti hanno accesso a laboratori all'avanguardia nel settore della neurochimica e della neurologia sperimentale. Il team di ricerca multidisciplinare, composto da neurologi, neuropsicologi, psichiatri, biologi e biofisici, garantisce un approccio completo. Le attività didattiche all'interno del curriculum valorizzano sia gli aspetti clinici che quelli di ricerca sperimentale preclinica, includendo approcci di analisi statistica avanzata per la diagnosi precoce e la prognosi (es. machine learning). Le attività di ricerca clinica includono: 1) studio dei biomarcatori nel liquido cerebrospinale e nel sangue come strumenti diagnostici e prognostici nelle malattie degenerative e autoimmuni del sistema nervoso centrale (biomarcatori di amiloidosi, tauopatia, neurodegenerazione e danno assonale, danno e disfunzione sinaptica, disfunzione delle cellule gliali, immunità adattativa); 2) studio dei biomarcatori su altre matrici (mucosa olfattiva, biopsia cutanea); 3) seed amplification assay di alfa-sinucleina in diverse matrici; 4) modelli applicativi di machine learning per la diagnosi precoce e la prognosi delle malattie neurodegenerative e neuroinfiammatorie; 6) determinanti fisiologici del controllo motorio e analisi biomeccanica dell'attivazione muscolare; 7) patogenesi dei disturbi psichiatrici e manifestazioni psicopatologiche nelle malattie neurologiche ;8) identificazione delle caratteristiche cliniche e dei pattern elettrofisiologici nelle epilessie ad esordio tardivo. Nel campo preclinico, la ricerca mira a indagare: 1) la patogenesi molecolare della disfunzione sinaptica durante lo sviluppo di disturbi infiammatori e degenerativi del sistema nervoso centrale, con particolare attenzione ai meccanismi alla base della perdita della plasticità sinaptica, quali il potenziamento/depressione a lungo termine e il depotenziamento sinaptico; 2) lo studio della funzione sinaptica e delle sue implicazioni sull'attività delle reti cerebrali, sulla cognitività e sul comportamento, attraverso indagini elettrofisiologiche, biochimiche, istologiche e comportamentali in modelli sperimentali di sclerosi multipla, malattia di Parkinson, malattia di Alzheimer e di alcune forme genetiche di epilessia. Gli studenti del dottorato saranno invitati a partecipare a riunioni nazionali della Società Italiana di Neurologia (SIN), della Società Italiana di Medicina di Laboratorio (SiBioc), della Società Italiana delle Neuroscienze (SINS), dell'Associazione Autonoma Affiliata alla SIN per la Demenza (SINDem), dell'Associazione Italiana di Neuroimmunologia (AINI), della Federazione Italiana Sclerosi Multipla (FISM), della Lega Italiana contro la malattia di Parkinson (LIMPE/DISMOV), della Lega Italiana contro l'Epilessia (LICE) e a riunioni internazionali della European Association of Neurology (EAN), American Academy of Neurology (AAN), Society for CSF Analysis and Clinical Neurochemistry, Alzheimer’s Association International Conference (AAIC), Movement Disorders Society (MDS) and AD/PD international conferences, European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) and Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS), per presentare i dati della loro attività di ricerca e collaborare con altri gruppi di ricerca italiani e stranieri.

COLLABORAZIONI INTERNAZIONALI: Amsterdam UMC, Paesi Bassi (Prof. Charlotte Teunissen); Università di Halle, Germania (Prof. Markus Otto); Università di Gothenburg, Svezia (Prof. Henrik Zetterberg, Prof. Kaj Blennow); Università di Doha, Qatar (Prof. Omar El Agnaf); New York University, NY, USA (Prof. Nicolas Tritsch); Barcelonaβ, Spagna (Dott.ssa Marta del Campo); Parkinson's Foundation NY, USA; Michael J Fox Foundation, USA; Amprion Inc., San Diego, CA, USA (Dott. Luis Concha Marambio); ADx Neurosciences, Belgio (Dott. Erik Stoops, Dott. Eugeen Vanmechelen); Fujirebio Europe, Belgio (Dott.ssa Nathalie Le Bastard); International Consortium of Clinics for Elderly with Epilepsy (ICCEE) Prof. Rebecca O’Dwyer, Department of Neurological Sciences, Chicago (USA); International Post-Stroke Epilepsy Research Consortium (IPSERC) (Prof. Patrick Kwan Department of Neurosciences, Melbourne, Australia and Prof. Nishant K. Mishra Division of Stroke Vascular Neurology, Department of Neurology, Yale University School of Medicine, Connecticut).

AFFILIAZIONI A GRUPPI DI LAVORO ITALIANI: Fresco Parkinson Network; Gruppo di studio RIREMS (Raising Italian Researchers in Multiple Sclerosis); Gruppo di studio (insieme all’Istituto Neurologico Carlo Besta di Milano e al Centro Neurolesi Bernardino-Pulejo di Messina) per la diagnosi molecolare non invasiva della malattia di Parkinson.

• Scienze Chirurgiche

Il curriculum scienze chirurgiche sviluppa studi e ricerche in vari ambiti della diagnostica e terapia. La formazione dei ricercatori prevede argomenti di urologia, diagnostica per immagini, otorinolaringoiatria e chirurgia oncologia. Nell’ambito urologico di particolare rilievo è lo sviluppo della tecnica robotica per la chirurgia del tratto urinario per patologia neoplastica. Il progetto di dottorato offre la formazione nello studio della patologia urinaria funzionale con particolare rilievo alla patologia del pavimento pelvico.

Nel percorso formativo è garantito l’accesso alla multidisciplinarietà con collaborazione e sviluppo di conoscenze nella oncobiologia con studi riguardanti markers tumorali. I docenti impegnati nella disciplina diagnostica per immagini eseguono e guidano ricerche sullo sviluppo delle tecniche di RMN nella diagnostica delle principali affezioni di ghiandole ed organi parenchimatosi. Particolare focus è la diagnostica urogenitale mediante tecniche non-invasive. Il ricercatore in formazione deve dimostrare con capacità crescente di dare valore alla capacità diagnostica ed i limiti della metodica. In questo ambito diagnostico è favorito il confronto con altre metodiche in un setting collegiale nell’ambito del dipartimento che ospita il dottorando al fine di favorire idee e progettualità. La disciplina ORL favorisce l’acquisizione nell’ambito soprattutto audiologico e laringologico. La diagnostica delle affezioni dell’organo di senso è sviluppato in collaborazione stretta con il curriculum neuroscienze. Il recupero della funzione uditiva e gli aspetti chirurgici delle affezioni del distretto testa-collo. Nell’ambito della Chirurgia toracica, sono sviluppati filoni di ricerca pre-clinica, clinica e di sviluppo tecnologico. In collaborazione con il gruppo oncologico multidisciplinare per la patologia polmonare sono attive ricerca osservazionali sui fattori prognostici del cancro del polmone e sui trattamenti integrati. E’ di notevole interesse il trattamento chirurgico per i tumori della parete toracica. In tale ambito è sviluppato un filone di ricerca sulle metodiche di ricostruzione protesica mediante materiali sintetici (protesi personalizzate, 3D printing), autologhi (sviluppo di tecniche chirurgiche plastiche) e trapianto (osso da cadavere). Nell’ambito dello sviluppo tecnologico in chirurgia, la chirurgia toracica sviluppa metodologie per la chirurgia mini-invasiva fast-track ed è centro di riferimento per la chirurgia ricostruttiva bronco-vascolare per tumore polmonare localmente avanzato. Nei riguardi della ricerca preclinica, sono attivi progetti di ricerca sperimentale su grande modello animale riguardanti crescita polmonare compensatoria, prevenzione delle complicanze chirurgiche, test armamentario chirurgico e agente pleurodesico.

Lo sviluppo delle competenze seguirà il seguente schema annuale. Primo anno: principi di chirurgia oncologica ed applicazioni in ambito diagnostico e terapeutico secondo anno: la chirurgia toracica nei tumori solidi e nei linfomi, la chirurgia nelle manifestazioni extra-midollari delle emopatie maligne terzo anno: le metodiche invasive per la diagnosi in oncologia. Le tecniche chirurgiche e i biomarcatori in oncologia.

Nel corso del triennio, viene favorita la frequenza a congressi e convegni delle discipline di riferimento dell’iscritto.

Il curriculum scienze chirurgiche offre la possibilità di affinare conoscenze ponte tra la medicina moderna del “micro”, la system biology, la medicina di precisione e l’arte chirurgica.

Il curriculum “scienze chirurgiche” vanta numerose collaborazioni con scuole estere (Harvard medical School, Shanghai Pulmonary Hopital e Washington University School of Medicine in St. Louis, altre).

• Biotecnologie in Ematologia, Terapie Cellulari e nel Trapianto di Midollo Osseo Umano

Gli obiettivi del Curriculum sono la formazione di ricercatori autonomi altamente specializzati in settori specifici di una ricerca in campo biomedico emato-oncologico che è incentrata sul paziente. Infatti, le attività didattiche in questo Curriculum oltre a comprendere incontri di tipo teorico, sono fortemente incentrate anche su attività cliniche e discussioni secondo il formato "clinical case report". Il Curriculum offre l’accesso a laboratori di diagnostica e ricerca avanzata con le tecniche e metodiche più innovative nel settore della diagnosi e terapia delle patologie emato-oncologiche e della ricerca preclinica, che negli ultimi anni è in rapida evoluzione.

Focus di programma includono: 1) Le cellule staminali ematopoietiche: identificazione, separazione, arricchimento, caratteristiche biologiche e modelli in vitro e in vivo di staminalità e trasformazione leucemica. Studio per l’impiego in programmi di trapianto innovativi. Uso in modelli preclinici murini per diversi obiettivi di ricerca; 2) Cellule T/NK ingegnerizzate per terapia cellulare (CAR-T/CAR-NK): principi, antigen-discovery, disegno, produzione, tecnologie di ingegneria genetica e applicazioni pratiche in diversi settori. Uso in modelli preclinici murini e /o umanizzati per studi di tossicità e proof-of-concept di efficacia; 3) Cellule T-regolatorie: principi, identificazione, separazione, arricchimento, caratteristiche biologiche e modelli in vitro e in vivo per lo studio delle loro funzioni in diversi settori, di trapianto e non. Uso in modelli preclinici murini e /o umanizzati per studi di proof-of-concept; 3) Anticorpi monoclonali: uso nella diagnostica e nella terapia, e metodiche di produzione e test applicativi. 4) Training sulle metodologie di studio del genoma: citogenetica convenzionale - FISH - Next Generation Sequencing - utilizzo e interpretazioni. 5) Training e applicazione delle tecniche di Trascriptomica e proteomica; 6) Targeted therapy e drug discovery/development: principi, impieghi attuali e ricerca applicata alle patologie onco-ematologiche; 7) Ricerca clinica di Fase 1; 8) studio dei meccanismi alla base delle complicanze post-trapianto.

I dottorandi saranno invitati a partecipare a convegni nazionali (Società Italiana di Ematologia, SIE; Società Italiana di Ematologia Sperimentale, SIES; altri) e internazionali (European Hematology Association, EHA; American Society of Hematology, ASH; altri) di interesse per la loro ricerca, a presentare i risultati della loro attività e a collaborare con altri gruppi di ricerca italiani e stranieri.

COLLABORAZIONI INTERNAZIONALI: Columbia, University, NY, USA (Prof R Dalla Favera); Dana Farber, Boston, USA (Prof K Stegmaier); University of New Castle Upon Tyne, Inghilterra (Prof C Harrison, Prof A Moorman); University of Ghent, Belgio (Prof P Van Vlierberghe); Center for Human Genetics and VIB, Lovanio, Belgio (Prof J Cools); Department of Radiation Oncology, City of Hope National Medical Center, Duarte, CA, USA (Prof S Hui); Munich-Leukemia-Laboratory (MLL), Munich, Germany (Prof. Torsten Haferlach, Prof. Claudia Haferlach); INSERM/CNRS, Paris, France (Prof. Hugues de Thé); University of Bergen, Bergen, Norway (Prof. Bjørn Tore Gjertsen); Institute of Cell Biology (Cancer Research), Frankfurt, Germany (Prof R Küppers); Hairy Cell Leukemia Foundation; MDAnderson Cancer Center (MDACC) (Prof. Marina Konopleva), Houston, Texas.

AFFILIAZIONI A GRUPPI DI LAVORO ITALIANI: GIMEMA working groups, GITMO (Gruppo Italiano Trapianto di Midollo Osseo), CAMPUS ALL (Leucemie Acute Linfoblastiche), FIL (Federazione Italiana Linfomi); Hematology, Universities of: Roma La Sapienza, Roma Tor Vergata, Parma, Pescara, Bari, Lecce, Milano San Raffaele, Verona, Ferrara, Modena, Torino Le Molinette, Siena, Careggi Firenze, Palermo, Cagliari.

• Radioterapia Oncologica

Gli obiettivi del Curriculum sono la formazione di ricercatori autonomi altamente specializzati in settori specifici di una ricerca in campo radioterapico. Le attività didattiche in questo Curriculum comprendono incontri di tipo teorico, ma anche discussione e valutazione di piani di cura e discussioni secondo il formato "clinical case report".

Focus di programma includono: 1) Integrazione della radioterapia con marcatori biomolecolari e nuovi trattamenti. 2) Sviluppo di strumenti di radiomica per predire la risposta ai trattamenti radianti.

3) Principi di radiobiologia. 4) Integrazione tra terapie sistemiche e radioterapia in onco-ematologia.

5) Apparecchiature e tecniche di radioterapia. 6) Ricerca clinica nell'impiego di tecniche speciali di radioterapia (Brachiterapia HDR, Radioterapia stereotassica, Radiochirurgia). 7) Tecniche di radioterapia nel condizionamento al trapianto di cellule staminali ematopoietiche (Total Body Irradiation e Total Marrow/Lymphoid Irradiation), radioterapia come trattamento bridge in pazienti che riceveranno terapia con CAR T. 8) Parametri clinici, dosimetrici e biomolecolari predittivi di outcome in pazienti trattati con Total Marrow/Lymphoid Irradiation. 9) Ricerca traslazionale: ruolo del microbiota in radioterapia.

I dottorandi saranno invitati a partecipare a convegni nazionali ed internazionali di interesse per la loro ricerca, a presentare i risultati della loro attività e a collaborare con altri gruppi di ricerca italiani e stranieri

COLLABORAZIONI NAZIONALI: SS Radioterapia Pediatrica, Fondazione (IRCCS) Istituto Nazionale dei Tumori di Milano, Dipartimento di Radioterapia, Centro Nazionale di Adroterapia Oncologica, Pavia; Sezione di Radioterapia, IRCCS Istituto Tumori Regina Elena, Roma; Dipartimento di Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma; Divisione di Radioterapia Oncologica, IEO, Istituto Europeo di Oncologia IRCCS, Milano

COLLABORAZIONI INTERNAZIONALI: Department of Radiation Oncology, City of Hope National Medical Center, CA, United States; Department of Radiation Oncology, Iridium Kankernetwerk, Antwerp, Belgium, Faculty of Medicine and Health Sciences, Antwerp, Belgium; Radiation Oncology (Maastro), GROW School for Oncology and Developmental Biology, Maastricht University Medical Centre, Maastricht, the Netherlands; Department of Experimental Clinical Oncology, Department of Oncology, Danish Centre for Particle Therapy, Aarhus University Hospital, Aarhus, Denmark; Department of Oncology, University of Cambridge, UK¸ Radiation Oncology Department, Universitat Rovira I Virgili, Hospital Universitari Sant Hoan de Reus, IISPV, Spain; Department of Radiation Oncology, University Hospital HM Sanchinarro, HM Hospitales, Madrid, Spain; Service of Brachytherapy, Department of Image and Radioncology, Instituto Português Oncologia Porto Francisco Gentil E.P.E., Portugal; Radiation Oncology, ICM-Val d′ Aurelle, Univ Montpellier, Montpellier, France; Division of Radiation Oncology, Institute of Oncology Ljubljana, Ljubljana, Slovenia; Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia; Radiotherapy Unit, Medical School, National and Kapodistrian University of Athens, Greece; Department of Radiation Oncology, Koc University, Faculty of Medicine,Istanbul, Turkey.

AFFILIAZIONI A GRUPPI DI LAVORO ITALIANI: Gruppo di studio AIRO (Associazione Italiana di Radioterapia ed Oncologia clinica) mammella. Gruppo di studio AIRO neoplasie Ginecologiche, Gruppo di studio AIRO neoplasie gastro-intestinali, FIL (Federazione Italiana Linfomi), AIEOP (Associazione Italiana di ematologa ed Oncologia Pediatrica)

Curricula

• Pathology and Clinic of Atherosclerosis and Aging

Study of lipid and carbohydrate metabolism, vascular risk factors and immuno-inflammatory response in the pathophysiology of atherosclerotic vascular damage.

Identification of atherosclerosis biomarkers and evaluation of the pathophysiological processes of age-related diseases. Interaction between infectious processes of different etiology and metabolic disorders and arterial vascular homeostasis.

Physiopathological bases of glucose and lipid metabolism and the action of risk factors for atherosclerotic disease, metabolic syndrome, hepatic steatosis.

Identification and use of molecular, biohumoral, and functional markers of atherosclerosis and of the main age-related pathologies.

Pre-clinical and clinical studies for the characterization and modulation of biomarkers of aging and age-related pathologies, particularly cellular senescence, telomere alterations, inflammation, epigenetic alterations, and altered intercellular communication. Identification of innovative markers based on metabolomics approaches.

Innate immunity and immune tolerance, role in cardio-metabolic and inflammatory diseases in aging, in age-related pathologies, in frailty syndrome.

Pathophysiological and clinical characterization of physical and cognitive frailty and the main geriatric syndromes, particularly delirium, falls, and fragility fractures.

Clinical studies for the identification of the biological, pathophysiological, and clinical-care determinants of functional and health outcomes in the old age subject in the acute setting, in particular the orthogeriatric one.

Clinical studies to identify precision medicine strategies.

Feasibility and effectiveness studies of procedures and new organizational-care models.

Study of host-pathogen interactions mainly focused on the pathogenesis and advanced diagnostics (including Next Generation Sequencing technology) of time-dependent infections, infections by multi-drug resistant organisms (MDRO), and pathogens of epidemic or pandemic relevance.

The objectives of the Curriculum are the training of highly specialized autonomous researchers in specific sectors of biomedical research that address subjects with clinical complexity and the biological processes underlying cardiovascular pathologies, aging, and infections.

INTERNATIONAL COLLABORATIONS: Karolinska Institute, Stockholm, Sweden Department of Neurobiology, Care Sciences and Society, (Prof. Eric Westman, Prof. Silvia Maioli, Prof. Francesca Mangialasche, Prof. Bengt Winblad), Aging Research Center-ARC (Prof. Laura Fratiglioni), Center for Alzheimer Research (CAR) (Prof. Daniel Ferreira Padilla, Prof. Dorota Religa); Brain Health Institute, Stockholm, Sweden (Prof. Miia Kivipelto); Institute of Clinical Medicine, Neurology, University of Eastern Finland, Kuopio, Finland (Prof. Alina Solomon); Department of Public Health and Welfare, Finnish Institute for Health and Welfare, Helsinki, Finland (Prof. Tiia Ngandu); Department of Neurology, Medical University of Vienna, Austria (Prof. Elizabeth Stögmann ); FH Joanneum, Graz, Austria (Prof. Sten Hanke) University Medical Center, UMC, Amsterdam, Netherlands (Prof. Wiesje van der Flier); Université de Lille, Inserm, CHU Lille, Institut Pasteur de Lille, France (Prof. Jean-Charles Lambert); Human Nutrition Unit, Biochemistry and Biotechnology Department, University Hospital of Sant Joan de Reus, IISPV, Rovira i Virgili University, Reus, Spain (Prof. Jordi Salas Salvadò); Translational Health Sciences, Bristol Medical School, University of Bristol, United Kingdom (Prof. Patrick Kehoe); Ageing Clinical Research, Department II of Internal Medicine and Center for Molecular Medicine, University Hospital Cologne, University of Cologne, Germany (Prof. Maria Cristina Polidori); Department of Medicine, Academy of Applied Medical and Social Sciences—AMiSNS: Akademia Medycznych I Spolecznych Nauk Stosowanych, Elbląg, Poland (Prof. Luigi Marano); Electrical and Computer Engineering Department, ESDA Lab, Professor University of Peloponnese, Greece (Prof. Nikolaos Voros); Department of Orthopaedics, University Hospital of Patras, Greece (Prof. Elias Panagiotopoulos); Department of Clinical Gerontology, Robert-Bosch-Hospital, Stuttgart, Germany (Prof. Clemens Becker); Department of Geriatrics and Geriatric Rehabilitation, Lausanne University Hospital, Lausanne, Switzerland (Prof. Patrizia D'Amelio); Pôle Maladies du Vieillissement, Gérontologie Et Soins Palliatifs, Université de Lorraine, Nancy, France (Prof. Athanase Benetos); Alzheimer's Center at Temple, Lewis Katz School of Medicine, Temple University, Philadelphia, USA (Prof. Domenico Praticò); Department of Chemistry and Sanders-Brown Center on Aging, University of Kentucky, Lexington, USA (Prof. Allan D. Butterfield); Longevity Institute and Davis School of Gerontology, University of Southern California, Los Angeles, USA (Prof. Valter Longo); Longitudinal Studies Section, Translational Gerontology Branch, National Institute on Aging, Baltimore, USA (Prof. Luigi Ferrucci); Center for Cell Signaling, Department of Microbiology, Biochemistry, and Molecular Genetics, New Jersey Medical School, Rutgers University, Newark, USA (Prof. Utz Herbig). Division of Cardiovascular Medicine, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden (Prof. Per Eriksson, Prof. Bruna Gigante, Prof. Rona J Strawbridge); Division of Medicine and Department of Clinical Sciences, Danderyd Hospital, Karolinska Institutet, Stockholm, Sweden (Prof. Louis Ziegler); Institute of Health and Wellbeing, University of Glasgow, UK (Prof. Rona J Strawbridge); Health Data Research, Clarice Pears Building, Glasgow, UK (Prof. Rona J Strawbridge); Cardiovascular Genetics, Institute Cardiovascular Science, University College London, UK (Prof. Steve E. Humphries); Lipidology and Cardiovascular Prevention Unit, Department of Nutrition, Sorbonne Université, INSERM UMR1166, APHP, Hôpital Pitié-Salpètriêre, Paris, France (Prof. Antonio Gallo); Unités de Prévention Cardiovasculaire, Assistance Publique-Hôpitaux de Paris, Service Endocrinologie-Métabolisme, Groupe Hospitalier Pitié-Salpétrière, Paris, France (Prof. Philippe Giral); Pitié-Salpetrière Hospital and Sorbonne University, Cardio metabolic Institute, Paris, France (Prof. Eric Bruckert); Department of Medicine, University Medical Center Groningen, Groningen & Isala Clinics Zwolle, Groningen, the Netherlands (Prof. Andries J Smith); Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio Campus, Kuopio, Finland (Prof. Sudir Kurl); Kuopio Research Institute of Exercise Medicine, Kuopio, Finland (Prof. Kai Savonen); Department of Clinical Physiology and Nuclear Medicine, Science Service Center, Kuopio University Hospital, Kuopio, Finland (Prof. Kai Savonen). Department of Medical Sciences, Uppsala University, Uppsala Science Park, Uppsala, Sweden (Prof. Lars Lind); Department of Cardiology, Danderyd University Hospital, Stockholm, Sweden (Prof. Bruna Gigante); Department of Preventive Cardiology and Lipidology, Medical University of Lodz (MUL), Poland (Prof. Macjei Banach); Liverpool Centre for Cardiovascular Science, Liverpool, UK (Prof. Peter E. Penson); Department of Nutritional Sciences and Dietetics, International Hellenic University, Thessaloniki, Greece (Prof. Niki Katsiki); The Johns Hopkins Ciccarone Center for the Prevention of Heart Disease, Baltimore, MD, USA; Preventive Cardiology, CGH Medical Center, Sterling, USA (Prof. Dimitri P Mikhailidis, Prof. Peter Toth); Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran (Prof. Amirhossein Sahebkar); Department of Internal Medicine, University Hospital Centre Zagreb, School of Medicine University of Zagreb, Zagreb, Croatia (Prof. Zeljko Reiner); Clinica de Cardiologie, Institutul de Boli Cardiovasculare Timisoara, Timisoara, Romania (Prof. Dan Gaita).

ITALIAN AND INTERNATIONAL RESEARCH NETWORKS: REPOSI (REgistro dei pazienti per lo studio delle polipatologie e POliterapie in reparti della rete Simi); AEQUI (Aged European population QUality of life in Infectious diseases); International Lipid Expert Panel (ILEP); Piattaforma IMPROVE; European Atherosclerosis Society Familial Hypercholesterolaemia Studies Collaboration; Lipid Clinics Network Group; Rete LIPIGEN Study Group; Rete LIPIGEN Paediatric Group; Centro Cardiologico Monzino, Milano; Italian COVID Group; Intensive Care, Infectious Diseases COVID-19 Study Group; ADA Group; TSUNAMI Study group.

• Neurosciences

The Neuroscience Curriculum focuses on the study of pathogenetic mechanisms and novel biomarkers in various neurological diseases, such as neurodegenerative diseases, neuroinflammatory diseases, headaches, and epilepsy. Students have access to state-of-the-art laboratories in neurochemistry and experimental neurology. The multidisciplinary research team of neurologists, neuropsychologists, psychiatrists, biologists, and biophysicists ensures a comprehensive approach. Teaching activities within the curriculum enhance both clinical and preclinical experimental research aspects, including advanced statistical analysis approaches for early diagnosis and prognosis (e.g., machine learning).

Clinical research activities include: 1) study of biomarkers in cerebrospinal fluid and blood as diagnostic and prognostic tools in degenerative and autoimmune diseases of the central nervous system (biomarkers of amyloidosis, tauopathy, neurodegeneration and axonal damage, synaptic damage and dysfunction, glial cell dysfunction, adaptive immunity); 2) study of biomarkers on other matrices (olfactory mucosa, skin biopsy); 3) seed amplification assay of alpha-synuclein in different matrices; 4) machine learning application models for early diagnosis and prognosis of neurodegenerative and neuroinflammatory diseases; 6) physiological determinants of motor control and biomechanical analysis of muscle activation; 7) pathogenesis of psychiatric disorders and psychopathological manifestations in neurological diseases ;8) identification of clinical features and electrophysiological patterns in late-onset epilepsies. In the preclinical field, research aims to investigate: 1) the molecular pathogenesis of synaptic dysfunction during the development of inflammatory and degenerative disorders of the central nervous system, with a focus on the mechanisms underlying the loss of synaptic plasticity, such as long-term potentiation/depression and synaptic depotentiation; 2) the study of synaptic function and its implications on brain network activity, cognition, and behavior through electrophysiological, biochemical, histological, and behavioral investigations in experimental models of multiple sclerosis, Parkinson's disease, Alzheimer's disease, and some genetic forms of epilepsy. PhD students will be invited to participate in national meetings of Italian Society of Neurology (SIN), of Italian Society of Laboratory Medicine (SiBioc), Italian Society for Neurosciences (SINS), Autonomous Association Affiliated with SIN for Dementia (SINDem), Italian Association of Neuroimmunology (AINI), Italian Federation for Multiple Sclerosis (FISM), Italian League for Parkinson’s disease (LIMPE/DISMOV), Italian League against Epilepsy (LICE) and international meetings of the European Association of Neurology (EAN), American Academy of Neurology (AAN), Society for CSF Analysis and Clinical Neurochemistry, Alzheimer’s Association International Conference (AAIC), Movement Disorders Society (MDS) and AD/PD international conferences, European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) and Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) international conferences, to present data from their research activity and to collaborate with other Italian and foreign research groups.

INTERNATIONAL COLLABORATIONS: Amsterdam UMC, The Netherlands (Prof. Charlotte Teunissen); Halle University, Germany (Prof. Markus Otto), University of Gothenburg, Sweden (Prof. Henrik Zetterberg, Prof. Kaj Blennow); Doha University, Qatar (Prof. Omar El Agnaf); New York University, NY, USA (Prof. Nicolas Tritsch); Barcelonaβ, Spain (Dr. Marta del Campo); Parkinson’s Foundation NY, USA; Michael J Fox Foundation, USA; Amprion Inc., San Diego, CA, USA (Dr. Luis Concha Marambio), ADx Neurosciences, Belgium (Dr. Erik Stoops, Dr. Eugeen Vanmechelen); Fujirebio Europe, Belgium (Dr. Nathalie Le Bastard); International Consortium of Clinics for Elderly with Epilepsy (ICCEE) Prof. Rebecca O’Dwyer, Department of Neurological Sciences, Chicago (USA); International Post-Stroke Epilepsy Research Consortium (IPSERC) (Prof. Patrick Kwan Department of Neurosciences, Melbourne, Australia and Prof. Nishant K. Mishra Division of Stroke Vascular Neurology, Department of Neurology, Yale University School of Medicine, Connecticut).

ITALIAN GROUPS AFFILIATIONS: Fresco Parkinson Network; RIREMS study group (Raising Italian Researchers in Multiple Sclerosis). Study group (together with the Carlo Besta Neurological Institute in Milan and the Bernardino-Pulejo Neurolesi Center in Messina) for noninvasive molecular diagnosis of Parkinson's disease.

• Surgical Sciences

The surgical sciences curriculum develops studies and research in various areas of diagnostics and therapy. The training of researchers includes topics in urology, diagnostic imaging, ENT and surgical oncology. In the urological field, the development of the robotic technique for urinary tract surgery for neoplastic pathologies is of particular importance. The doctoral project offers training in the study of functional urinary pathology with particular emphasis on pelvic floor impairment.

In the training course, the access to multidisciplinarity is guaranteed with collaboration and development of knowledge in oncobiology by means of studies on tumor markers. The board members involved in the diagnostic imaging teaching carry out and guide research on the development of MRI techniques in the diagnosis of the main diseases of parenchymatous glands and organs. A particular focus is on urogenital diagnostics using non-invasive techniques. The researcher in training must demonstrate with increasing ability to give value to the diagnostic potentials and the limits of the method. In this academic area, the comparison with other methods is encouraged in a collegial setting within the department that hosts the doctoral student in order to encourage ideas and study planning. The ENT discipline favors acquisition in the audiological and laryngological fields especially. The diagnosis of sensory organ disorders is developed in close collaboration with the neuroscience curriculum. The recovery of hearing function and the surgical aspects of head and neck disorders are routinely investigated. In the field of thoracic surgery, research lines of pre-clinical, clinical and technological development trials are developed. In collaboration with the multidisciplinary oncology observational research is active on the prognostic factors of lung cancer as well as urinary bladder, liver, prostate and on integrated treatments. Surgical treatment for chest wall tumors is of considerable interest. In this context, a line of research has been developed on prosthetic reconstruction methods using synthetic materials (personalized prostheses, 3D printing), autologous (development of plastic surgical techniques) and transplantation (cadaver bone). As part of technological development in surgery, thoracic surgery develops methodologies for fast-track minimally invasive surgery and is a reference center for bronchovascular reconstructive surgery for locally advanced lung cancer. With regards to preclinical research, experimental research projects on large animal models are active regarding compensatory lung growth, prevention of surgical complications, testing of new surgical devices and pleurodesic agents.

Skills development will run the following annual schedule. First year: principles of oncological surgery and applications in diagnostic and therapeutic fields; second year: thoracic surgery in solid tumors and lymphomas, surgery in extra-medullary manifestations of malignant blood disorders; third year: invasive methods for diagnosis in oncology. Surgical techniques and biomarkers in oncology.

During the three-year period, attendance at congresses and conferences in the disciplines of reference of the member is encouraged.

The surgical sciences curriculum offers the opportunity to refine bridge knowledge between modern "micro" medicine, system biology, precision medicine and surgical art.

The "surgical sciences" curriculum boasts numerous collaborations with foreign schools (Harvard Medical School, Shanghai Pulmonary Hopital and Washington University School of Medicine in St. Louis, others).

• Biotechnology in Hematology, Cellular Therapies and Human Bone Marrow Transplantation

The objectives of the Curriculum are the training of highly specialized independent researchers in specific sectors of patient-centred biomedical hemato-oncology research. The teaching activity of this Curriculum, in fact, in addition to providing theoretical meetings, is also strongly focused on clinical activities and discussions according to the "clinical case report" format. The Curriculum offers access to advanced diagnostic and research laboratories with the most innovative techniques and methods in the sector of diagnosis and therapy of hemato-oncological diseases and preclinical research, which has been evolving rapidly in recent years.

Program focuses include: 1) Hematopoietic stem cells: identification, separation, enrichment, biological characteristics and in vitro and in vivo models of stemness and leukemic transformation. Study for use in innovative transplant programs. Use in preclinical mouse models for various research objectives; 2) Engineered T/NK cells for cell therapy (CAR-T/CAR-NK): principles, antigen-discovery, design, production, genetic engineering technologies and practical applications in different sectors. Use in preclinical murine and/or humanized models for toxicity studies and proof-of-concept of efficacy; 3) Regulatory T cells: principles, identification, separation, enrichment, biological characteristics and in vitro and in vivo models for the study of their function in different sectors, transplantation and otherwise. Use in preclinical murine and/or humanized models for proof-of-concept studies; 3) Monoclonal antibodies: use in diagnostics and therapy, and production methods and application tests. 4) Training on genome study methodologies: conventional cytogenetics - FISH - Next Generation Sequencing - use and interpretations. 5) Training and application of Transcriptomics and Proteomics techniques; 6) Targeted therapy and drug discovery/development: principles, current uses and research applied to onco-haematological diseases; 7) Phase 1 clinical research; 8) Studies of mechanisms underlying complications post-transplant.

Doctoral students will be invited to participate in meeting of national (Italian Society of Hematology, SIE; Italian Society of Experimental hematology, SIES) and international (European Hematology Association, EHA; American Society of Hematology, ASH) scientific societies of interest for their research, to present data from their research activity and to collaborate with other Italian and foreign research groups.

INTERNATIONAL COLLABORATIONS: Columbia, University, NY, USA (Prof R Dalla Favera); Dana Farber, Boston, USA (Prof K Stegmaier); University of New Castle Upon Tyne, Inghilterra (Prof C Harrison, Prof A Moorman); University of Ghent, Belgio (Prof P Van Vlierberghe); Center for Human Genetics and VIB, Lovanio, Belgio (Prof J Cools); Department of Radiation Oncology, City of Hope National Medical Center, Duarte, CA, USA (Prof S Hui); Munich-Leukemia-Laboratory (MLL), Munich, Germany (Prof. Torsten Haferlach, Prof. Claudia Haferlach); INSERM/CNRS, Paris, France (Prof. Hugues de Thé); University of Bergen, Bergen, Norway (Prof. Bjørn Tore Gjertsen); Institute of Cell Biology (Cancer Research), Frankfurt, Germany (Prof R Küppers); Hairy Cell Leukemia Foundation; MDAnderson Cancer Center (MDACC) (Prof. Marina Konopleva), Houston, Texas.

ITALIAN GROUPS AFFILIATIONS: GIMEMA working groups, GITMO (Gruppo Italiano Trapianto di Midollo Osseo), CAMPUS ALL (Leucemie Acute Linfoblastiche), FIL (Federazione Italiana Linfomi); Hematology, Universities of: Roma La Sapienza, Roma Tor Vergata, Parma, Pescara, Bari, Lecce, Milano San Raffaele, Verona, Ferrara, Modena, Torino Le Molinette, Siena, Careggi Firenze, Palermo, Cagliari.

• Radiotherapy in Oncology

The objectives of the Curriculum are the training of highly specialized independent researchers in specific sectors of radiation therapy  research. The teaching activity of this Curriculum, in fact, in addition to providing theoretical meetings, is also focused on treatment plans evaluation and discussions according to the "clinical case report" format.

Program focuses include: 1) Integration of radiotherapy (RT) with biomolecular markers and new treatments. 2) Development of radiomics tools to predict response to radiation therapy. 3) Principles of radiobiology; 4) Integration of systemic therapies and RT in onco-haematology. 5) Clinical research on the use of special RT techniques. (HDR Brachytherapy, Stereotactic radiotherapy, radiosurgery). 6) Total body irradiation and total marrow/lymphoid irradiation and RT as a bridge treatment in patients undergoing CAR T cell therapy. 7) Clinical, dosimetric and biomolecular parameters predictive of outcome in patients treated with Total marrow/lymphoid irradiation. 8) Translational research on the role of the microbiota in radiation treatment.

Doctoral students will be invited to participate in meeting of national and international scientific societies of interest for their research, to present data from their research activity and to collaborate with other Italian and foreign research groups.

NATIONAL COLLABORATIONS: Pediatric Radiotherapy Unit, Fondazione IRCCS Istituto Nazionale Tumori, Mila; Radiation Oncology Unit, Clinical Department, National Center for Oncological Hadrontherapy (CNAO), Pavia: Department of Radiation Oncology, IRCCS Regina Elena National Cancer Institute - IFO, Rome; Department of Radiation Oncology, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome; Division of Radiation Oncology, IEO, European Institute of Oncology IRCCS, Milan.

INTERNATIONAL COLLABORATIONS: Department of Radiation Oncology, City of Hope National Medical Center, CA, United States; Department of Radiation Oncology, Iridium Kankernetwerk, Antwerp, Belgium, Faculty of Medicine and Health Sciences, Antwerp, Belgium; Radiation Oncology (Maastro), GROW School for Oncology and Developmental Biology, Maastricht University Medical Centre, Maastricht, the Netherlands; Department of Experimental Clinical Oncology, Department of Oncology, Danish Centre for Particle Therapy, Aarhus University Hospital, Aarhus, Denmark; Department of Oncology, University of Cambridge, UK¸ Radiation Oncology Department, Universitat Rovira I Virgili, Hospital Universitari Sant Hoan de Reus, IISPV, Spain; Department of Radiation Oncology, University Hospital HM Sanchinarro, HM Hospitales, Madrid, Spain; Service of Brachytherapy, Department of Image and Radioncology, Instituto Português Oncologia Porto Francisco Gentil E.P.E., Portugal; Radiation Oncology, ICM-Val d′ Aurelle, Univ Montpellier, Montpellier, France; Division of Radiation Oncology, Institute of Oncology Ljubljana, Ljubljana, Slovenia; Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia; Radiotherapy Unit, Medical School, National and Kapodistrian University of Athens, Greece; Department of Radiation Oncology, Koc University, Faculty of Medicine,Istanbul, Turkey.

ITALIAN GROUPS AFFILIATIONS:

AIRO (Italian Association of Radiotherapy and Clinical Oncology) breast cancer study group, AIRO gynaecological tumors study group, AIRO gastrointestinal tumors study group, FIL (Italian Federation of Lymphomas), AIEOP (Italian Association of Paediatric Haematology and Oncology)