Graduate School in Translational Biomedicine Academic year

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1 Graduate School in Translational Biomedicine Academic year Translation research goes from bench to bedside, where theories emerging from preclinical experimentation are tested on disease-affected human subjects, and from bedside to bench, where information obtained from preliminary human experimentation can be used to refine our understanding of the biological principles underpinning the heterogeneity of human disease and polymorphism(s). Prof. F. Marincola

2 Center for Human Immunology and Inflammation CHI Directors Francesco Marincola, M.D., F.A.C.S. Chief, Infectious Disease and Immunogenetics Section in the Department of Transfusion Medicine, Clinical Center Dr. Marincola is Chief of the Infectious Disease and Immunogenetics Section in the Department of Transfusion Medicine at the Clinical Center of the National Institutes of Health in Bethesda, Maryland. Dr. Marincola received his MD, cum laude from the University of Milan, and his surgery training at Stanford University where he also completed a postdoctoral fellowship in surgical research. He joined the Surgical Oncology Branch of the National Cancer Institute, NIH, in Dr. Marincola is a NIH tenured senior investigator, Adjunct Professor, Peking Union Medical College, Beijing, China, Adjunct Professor, First Military Medical University, Tonghe, Guangzhou China, and a Member of the Board of Directors, International Society for Biological Therapy of Cancer. Dr. Marincola serves at the Editor-in-Chief, Journal of Translational Medicine and ASHI Quarterly; US Senior Editor of Immunotherapy, Associate Editor for The Journal of Immunotherapy, The Journal of Immunology, Tumori, and Clinical Cancer Research; Section Editor for Expert Opinion in Biological Therapy; Editorial Board, Cancer Immunology & Immunotherapy, The Journal of Experimental and Clinical Cancer Research. And Annals of Surgical Oncology. Dr. Marincola is an author of over 350 peer reviewed research articles and over 100 abstracts. He has been invited to speak at over 200 national and international meetings. Dr. Marincola is the second most cited scientist in melanoma during the last ten years, with 55 papers cited 3,704 times to date. Dr. Marincola s record includes 63 papers cited a total of 2,955 times to date in the field of Clinical Medicine and 51 papers cited a total of 2,204 times to date in the field of Immunology.

3 A major goal of the journal is to publish papers that identify and fill scientific knowledge gaps at the junction of basic research and human applications.

4 Da WIKIPEDIA Translational Medicine is an emerging view of medical practice and interventional epidemiology, as a natural 21st century progression from Evidence-Based Medicine. It integrates research inputs from the basic sciences, social sciences and political sciences to optimise both patient care and also preventive measures which may extend beyond the provision of healthcare services. Is the process of turning biological discoveries into drugs and medical devices that can help patients.

5 Translational Medicine at Stanford Philip Pizzo, MD Dean, Stanford University School of Medicine From my perspective, translational medicine can have both a narrow as well as a more general definition. Perhaps the most specific definition is "bench-to-bedside" research wherein a basic laboratory discovery becomes applicable to the diagnosis, treatment or prevention of a specific disease and is brought forth by either a physician-scientist who works at the interface between the research laboratory and patient care or by a team of basic and clinical science investigators. Translational medicine may also refer to the wider spectrum of patient-oriented research that embraces innovations in technology and biomedical devices as well as the study of new therapies in clinical trials. It also includes epidemiological and health-outcomes research and behavioral studies that can be brought to the bedside or ambulatory setting. Progetti a Stanford Istituti tematici dedicati a cancro, biologia delle cellule staminali, infezioni ed immunità, neuroscienze, malattie cardiovascolari

6 Medicina traslazionale: risultato di ricerca traslazionale Ricerca Traslazionale: continuum di 3 fasi Ricerca Traslazionale Fase 1 E l attività di ricerca esploratoria, che sviluppa trattamenti potenziali e verifica sicurezza ed efficacia, principalmente attraverso trials randomizzati. Classicamente sviluppata in contesto di Farmacoterapia, ha portato alla definizione/riconoscimento di Evidence Based Medicine Dal bancone al letto del malato Nuovo? Integrazione più articolata dei saperi, per esempio considerando anche l impatto e le conoscenze che derivano da punti di vista non farmaceutici (es psicologia, attività fisica, nutrizionismo, ecc)

7 Ricerca Traslazionale Fase 2 Valutazione di come ciò che è stato definito in fase 1 funziona nel contesto della pratica quotidiana Attività di ricerca: interfaccia delle tecnologie con fattori demografici e priorità sociali; elabora linee guida (bisogni, accettabilità, efficacia, costi) in un contesto ecologico finalizzato all ottimizzazione del management e dell utilizzo delle risorse. Coinvolgimento di altri partecipanti non professionali (consumatori)

8 Ricerca Traslazionale Fase 3 Aggiunge quanto serve per convertire in soluzioni sostenibili i trattamenti e le azioni preventive valutate in fase 2 (efficacia, costo) Attività di ricerca: per valutare l impatto di / guidare interventi governativi sulle attività di prevenzione e management Continuous Improvement Methodology (Kaizen)

9 Translational framework for public health research Ogilvie et al. BMC Public Health :116 doi: /

10 Key differences between the translational framework for public health research and the linear translational medicine pathway Characteristics of the translational framework for public health research Redefines the endpoint from that of institutionalising effective interventions to that of improving population health Incorporates the epidemiological traditions of population health surveillance and the identification of modifiable risk factors Reflects a spectrum of determinants of health from the individual to the collective level and a corresponding spectrum of levels of intervention Embraces a wide range of biomedical, social and environmental 'basic sciences' that have roles throughout the framework, not merely in supplying knowledge to be implemented Identifies a pivotal role for thoughtful and inclusive evidence synthesis Describes the iterative and bidirectional processes by which public health research and public health action may influence each other

11 NICE guidance on physical activity and the environment Case study The National Institute for Health and Clinical Excellence (NICE) provides evidence-based guidance for clinical practice in the National Health Service (NHS) in England. Each piece of guidance is based on the systematic review of evidence for the effectiveness and costeffectiveness of interventions and is subsequently translated into a set of implementation materials. In principle, the NICE process therefore fits neatly into the 'health technology assessment' component of the linear translational medicine pathway. However, NICE's remit was expanded in 2005 to include public health, and its recent guidance on physical activity and the environment illustrates the need for a more inclusive translational framework. Most intervention studies reviewed for this guidance were of comparatively low quality and few demonstrated unequivocal changes in physical activity. However, rather than conclude that the evidence was insufficient, the programme development group drew on other types of evidence admissible under NICE procedures including evidence about environmental correlates of physical activity, and interdisciplinary expert consensus to make constructive recommendations based on a more inclusive approach to evidence synthesis. Most recommendations were intended for recipients outside the NHS such as transport planners, who have not previously been the target of NICE guidance and are under no obligation to take account of it. The successful implementation of this guidance is therefore likely to depend more on the 'indirect insinuation' of the recommendations into the practice of those working outside the health sector, perhaps by articulating an additional, public health case for interventions primarily motivated by other aims such as reducing traffic

12 Dietary salt and blood pressure Case study A dose-response relationship between dietary salt intake and blood pressure has been consistently demonstrated in animal studies and in ecological, cohort and intervention studies in humans. A recent randomised controlled trial has also shown that dietary and behavioural counselling to limit salt intake reduces the incidence of 'hard' cardiovascular endpoints, thus surely fulfilling any reasonable definition of an evidence-based public health intervention. The linear model of translation suggests that all that remains is for 'sodium reduction interventions' of this kind to be implemented as widely as possible. However, an estimated 80% of dietary salt intake in Westernised countries comes from bread and processed foods rather than from discretionary use. Even if it were feasible to roll out intensive counselling across the population, shifting the population distribution of salt intake is therefore more likely to depend on changing the composition of processed foods. The greatest potential for translation into population health improvement may therefore lie not in disseminating and implementing a 'proven' intervention but in using other, predominantly epidemiological evidence to influence policymakers and the non-statutory corporate social responsibilities of food manufacturers. It may not be possible to demonstrate the populationlevel effectiveness (or otherwise) of regulatory interventions on food labelling or the salt content of processed foods until policymakers, somewhere, decide to intervene in this way as a 'natural experiment'; the effects could then be evaluated through enhanced population dietary and health surveillance

13 Problemi con il termine traslazionale Ogilvie et al. BMC Public Health :116 doi: / 'translation' and 'translational research' mean different things to different people. Differenze rispetto a dissemination o knowledge transfer The Canadian Institutes of Health Research (CIHR) define 'knowledge translation' in terms of exchange, synthesis, dialogue and interaction between researchers and users Diversi problemi di salute pubblica presentano una sfida applicative che esce dai limiti delle competenze del sistema sanitario. Questo è ambito di ricerca/azione traslazionale che non è però universalmente compreso

14 Journal of Translational Medicine Commentary Open Access Lost in Translation: Obstacles to Translational Medicine Stacey P Mankoff*1, Christian Brander2, Soldano Ferrone3 and Francesco M Marincola4 Abstract When we launched the Journal of Translational Medicine a few months ago, we were interested primarily in exploring scientific consideration of this discipline. However, as editors of JTM, we have been contacted almost daily to discuss the problems faced by scientists and clinicians around the world who are challenging the traditional boundaries of science and medicine. Through these conversations, we have learned that translational medicine is in fact "lost in translation," inspiring much angst, many promises and some Federal appropriations. However, little has been done to substantively promote this important field. Authoritative reviews on the subject are available to the interested reader [1-7]. In this article, we will address JTM's "constituency" to report what we've learned about the obstacles to translational medicine from the myriad of phone conversations and interactions.

15 Risposte ai problemi collegati con medicina traslazionale 1- Si parte con i piedi ben saldi (?) Philip Pizzo, MD, Dean, Stanford University School of Medicine supporting basic research is critical since it is often not possible to predict which of today's extraordinary ideas in basic science will lead to clinical applications in the future. Thus, a solid basic research program is vital for translational medicine to flourish. Thankfully Stanford's program in fundamental research is very strong. Translational research is usually based on incomplete understanding of biological mechanisms in : Lost in translation: Problems and pitfalls in translating laboratory observations to clinical utility, Richard Simon, European Journal of Cancer, Vol 44, Issue 18, December 2008, Pages UK: Cooksey report: linee guida al finanziamento della ricerca Aumentare finanziamento per ricerca traslazionale Istutuzione del Board for translational medicine under the auspices of the new crosscutting Office for Strategic Coordination of Health Research (OSCHR).

16 Pathway for translation of health research into healthcare improvement Source: A review of UK health research funding (the Cooksey report). Crown copyright Reproduced with permission. Ogilvie et al. BMC Public Health :116 doi: / Ist gap: the translation of basic and clinical research into ideas and products Bridging: preclinical development and early clinical trials II gap: introducing those ideas and products into clinical practice Bridging: health technology assessment, health services research and knowledge management

17 Risposte ai problemi collegati con medicina traslazionale Organizzazione e formazione Andrew S. Grove, the former chief executive of Intel, is taking the next step in his quest to infuse the engineering discipline of Silicon Valley into the development of new medical treatments. Mr. Grove has pledged $1.5 million so that the University of California campuses in San Francisco and Berkeley can start a joint master s degree program aimed at so-called translational medicine. The idea is to expose students to both the engineering prowess of Berkeley and the medical research of San Francisco to train a new breed of medical innovator. The best results are achieved through the cooperative efforts of different disciplines, all aimed at the same objective Collaboration is key

18 (non) Risposte ai problemi collegati con la medicina traslazionale Sistema della ricerca italiano organizzato in Dipartimenti/Istituti Formazione dottorale disciplinare

19 (primi tentativi di) Risposte ai problemi collegati con medicina traslazionale

20 Risposte ai problemi collegati con medicina traslazionale (Università di Verona)

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23 ARC - NET

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26 CENTRI DI RICERCA CardioVascular Risk network Centro di Genomica Funzionale delle Piante Stakeholders Università Azienda Ospedaliera ASL WHO Fondazione CariVerona Università Consorzio tutela Valpolicella Regione Veneto Opportunità finanziarie Verona Nanomedicine Initiative StartCup Veneto Sinergia ARC-NET International Cancer Genome Consortium Università Azienda Ospedaliera NIH Fondazione CariVerona Fondazione Cherubini Loro

27 Risposte ai problemi collegati con medicina traslazionale (Università di Verona) Formazione dottorale Scuola di Dotttorato in Scienze Biomediche Traslazionali Integrazione formativa trasversale da 6 curricula diversi dalla medicina legale alle scienze motorie

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29 Dottorato in Scienze Chirurgiche

30 Organizzazione della Scuola Direttore: funzioni di coordinamento organizzativo Comitato Scientifico: tre esperti esterni (Meldolesi, Sozzani, Bottinelli) valutazione, monitoraggio attività attribuzione risorse Consiglio della Scuola Coordinatore + 2 docenti + 1 studente/ogni corso di dottorato afferente alla Scuola Funzioni: organizzazione attività formative trasversali attribuzione risorse Collegio dei docenti dei singoli corsi di dottorato Organizzazione attività formativa specifica

31 Attività formative della Scuola Ricerca: ciascuno studente è affidato a tutor con CV e finanziamenti il tutor è responsabile del progetto di ricerca dello studente, anche per gli aspetti finanziari Formazione: tutor e studente uniti da contratto formativo che definisce le attività formative dello studente oltre all esecuzione del progetto di ricerca A fine anno verifica dell attività svolta e valutazione effettuata dal Collegio Docenti e dal Comitato Scientifico

32 Tipologia della formazione Responsabilità dei singoli corsi di dottorato Corsi tematici Corsi tecnologici Seminari/Conferenze (almeno 80 ore/anno) Partecipazione a Congressi nazionali ed internazionali Formazione Trasversale Di base: esempi Organizzazione di studi clinici Statistica Intellectual property Project management Skills: Communication PhD Day

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34 Progetti multidisciplinari Esiti della trasversalità Ricerca all interfaccia tra laboratorio e clinica Esempi diretti di collaborazione interna alla Scuola: Patologia Generale e Centro Fibrosi Cistica Chirurgia del Pancreas e ARC-NET Laboratorio Neurofarmacologia e Centro Cellule Staminali Bifari F, Decimo I, Chiamulera C, Bersan E, Malpeli G, Johansson J, Lisi V, Bonetti B, Fumagalli G, Pizzolo G, Krampera M. Novel stem/progenitor cells with neuronal differentiation potential reside in the leptomeningeal niche.j Cell Mol Med Sep;13(9B):

35 Conclusioni We are also working at the broader organizational level to develop institutes that will bring together basic and clinical scientists to address areas of translational medicine. I believe that the future success of translational medicine will be more readily achieved by educating and training medical and graduate students about the important interface that links medicine and science. Indeed it is my hope that the students we teach today will bring forth the translational research discoveries of tomorrow. Philip Pizzo, MD Dean, Stanford University School of Medicine