Aims of PhD program “Network Oncology and Precision Medicine” The proposed PhD program offers a training course based on the modern vision of oncology, driven on the design of the best treatment for every patient in the pursuit of personalized medicine. This topic is particularly important now since the different therapeutic approaches can be modulated following many options, according to specific needs and progression of the disease. This PhD program is addressed to students who have completed their degree in bio-medical or scientific-technological fields and will aim at building their skills regarding molecular oncology and Computational-based analysis. The main goal of the PhD program in “Network Oncology and Precision Medicine” is to train a new figure that will find his role in biomedical studies, joining different types of skills of the multidisciplinary branch of the network medicine in oncology, with the aim to better classify, diagnose, identify treatment and prevention strategies. Available technologies allow obtaining molecular and biological data from the patient in a short time and with relatively low cost. Currently, the clinical impact of this kind of information is still hampered by the lack of specific tools for successful integration with more “classical” data used in clinical practice. It is crucial, to obtain a personalized therapy with the highest success probability, to integrate clinical data together with molecular data, the availability of target therapies, data from clinical trials, basic and clinical research. The complexity and dynamic nature of the different types of data available for each oncology patient require new architectures, algorithms and networking strategies to be accessible to the oncologist that is taking care of the patient and to pharma industries, for the refinement and upgrading of therapeutic options. The shifting towards the “network medicine” method in oncology may represent a true improvement in the clinical management of oncological patients, optimizing early-stage diagnosis/screening programmes and therapeutic approach, with a likely reduction in expenses related to oncology patients, as postulated by precision medicine. The PhD program in “Network Oncology and Precision Medicine” aims at an educational path built on an interdisciplinary approach to the research topics with the focus on the identification of new biomarkers for precision medicine in oncology and on the development of new-generation models and algorithms based on “network medicine”, The educational path of the proposed PhD program is strongly supported by the highly collaborative environment of collaborations both at Sapienza University and with external research institutes, national and international. Academic disciplines included are general pathology, medical oncology, informatics, bio-engineering, processing systems, medical statistics, pharmacology, endocrinology, laboratory medicine, medical genetics and Pathological Anatomy. All the different expertise/skills are represented by the academic fields of the board members of the PhD program. 1) Regarding expertise on molecular and cellular pathology, microbiology and applied medical sciences and laboratory medicine, the following disciplines are included: MED/04 – General Pathology (Prof. Nuti, Ferretti, Rughetti, Gradini, Galuzzi) The field covers scientific and teaching activities, as well as a medical practice for general pathology and physiopathology. Basic research fields are molecular medicine and cellular pathology with a focus on oncology, immunology, immunopathology, genetic and epigenetic pathology. Of note, general pathology will set the basis for the educational path of the PhD program, since these notions are crucial for the later studies of the cellular and molecular mechanisms of cancer. MED/07 - Microbiology and Clinical Microbiology (Prof. Vernocchi e Prof. Putignani) This academic field deals with scientific and teaching activities on the mechanisms of microbial pathogenicity, host-pathogen interactions and microbial biotechnologies. Topics include bacteriology, virology, parasitology and clinical and diagnostic aspects of viral and microbial analyses. Recently, the crucial role of the microbiome in the response to oncological treatments was highlighted. Therefore, these topics will be included in the PhD program in “Network Oncology and Precision Medicine”. MED/46 – Laboratory Medicine (Prof. Pierelli, Po, Napoletano) This academic field deals with scientific and teaching activities in laboratory medicine. Topics will deal with technologies in clinical biochemistry, pathological histology, cytology, cytopathology, ultrastructural pathology and applied genetics. The PhD program addresses these subjects since they are the tools for the generation of different types of clinical data. MED/50 – Applied medical sciences (Prof. Malapelle) This academic field deals with scientific and teaching activities, as well as clinical practice regarding technologies for Diagnostic imaging and radiotherapy, critical care and emergency, hygiene and Environmental protection. Topics will include diagnostic methodologies, oncology treatments and the study of disease biomarkers. BIO/11 – Molecular Biology (Prof. Rajewsky) This academic field deals with the study of biological functions and post-transcriptional regulation of molecules involved in pathologies, the evolutive and biochemical properties of nucleic acids, interactions between nucleic acids and proteins, and protein-protein interaction. A specific focus will be the study of macromolecules involved in conservation, repair, duplication, transcription and translation of the information stored in the DNA, and macromolecules involved in the control of gene expression, proliferation, differentiation and malignant transformation. This scientific field offers innovative techniques in genetic engineering, bio-crystallography and bioinformatic tools for the biochemical characterization of biological macromolecules to PhD students. 2) Regarding expertise related to general and specialist medical oncology and surgery, diagnostic imaging and pathological anatomy, the following disciplines are included: MED / 06 - Medical oncology (Prof Marchetti, Prof. Botticelli, Prof. Curigliano, Prof. Pfister) The academic field includes scientific, educational-training and clinical practise in medical oncology. In this medical discipline, advanced technologies allow for the collection of numerous molecular and clinical data for each patient. The inclusion of this academic field in the course of the PhD in Network Oncology and Precision Medicine offers students training courses for the diagnosis of solid tumors and choice of anticancer therapies. Particular attention is paid to the development of innovative approaches based on a thorough understanding of the critical relationships between cancer cells and the microenvironment with particular attention to the tumor immune environment. MED/18 - Surgey (Prof. Petrucciani) This academic field incorporates scientific and didactic-training activities, as well as clinical care in the field of surgery. Clinical methodology, traditional and minimally invasive surgery in oncology are specific areas of expertise. The inclusion of this academic field in the course of the PhD in Network Oncology and Precision Medicine offers students the in-depth analysis of surgery in oncology. M-EDF / 02 Methods and Didactics of Sports Activities (Prof. Romanelli) The sector deals with the development of theories, techniques and methods for training and for the practice of different sports activities. Physical activity acts on essential mechanisms of the body such as metabolism, inflammation and the immune system and is therefore also important in cancer patients. Specifically, during the course of the PhD in Network Oncology and Precision Medicine, this discipline will be addressed to improve the quality of care and assistance to the patient. MED / 36 - Diagnostic Imaging and Radiotherapy (Prof. Panebianco) The academic field includes assistance, teaching and scientific activities in the field of diagnostic imaging and interventional radiology of organs and systems and nuclear medicine. Specific skills such as oncological radiotherapy and clinical radiological anatomy are addressed and this field is also interested in medical radiobiology. Specifically, the PhD in Network Oncology and Precision Medicine intends to investigate which imaging methods are most suitable for diagnostics, follow-up and evaluation of therapeutic responses in different tumors. In addition, innovative methods of radiation therapy are also addressed. MED / 08 - Pathological Anatomy (Prof. Giordano, Antonelli, Loda) This academic field is interested in scientific and didactic-training activities, as well as diagnostic assistance in the field of anatomy and pathological histology with specific skills in cyto-histopathology, histochemistry, immunohistochemistry, anatomical-pathological ultrastructural and molecular diagnostics and in anatomy and pathological specialist histology oncology. In this context, during the PhD useful information will be introduced to assist in the determination of personalized treatments in cancer patients. 3) Regarding expertise related to Information Processing Systems and Statistics, the following disciplines are included: ING-INF / 05 - Information Processing Systems (Prof. Armerini and Lenzerini) This academic field is interested in scientific disciplines related to the design and implementation of information processing systems, as well as their management and use in various application contexts with engineering methods and techniques. Theoretical foundations, methods and technically valid technologies fall within this sphere. These foundations, methods and technologies cover all aspects relating to a computer system, from hardware to software, from operating systems to computer networks, from databases to information systems, from programming languages. The inclusion of this academic field in the course of the PhD in Network Oncology and Precision Medicine is necessary in oncological medical research for the optimal processing and integration of molecular, clinical and other data (e.g. clinical trials) and will assist in the definition of the best clinical-diagnostic and therapeutic approach. MED / 01 - Medical Statistics (Prof. Strigari and Preissner) This academic field is interested in scientific and educational-training activities in the field of statistical and statistical-epidemiological methodologies applied to the biomedical and clinical fields, anthropometry and biometrics as well as to health planning and the organization and management of health services. The inclusion of this academic field in the training course of the PhD in Network Oncology and Precision Medicine is fundamental for the design, analysis and evaluation of experimental and observational studies in oncology. In addition, this discipline provides the knowledge and methodologies for the identification of tumor disease biomarkers. 4) Regarding expertise related to medical Pharmacology, the following disciplines are included: BIO / 14 - Pharmacology (Prof. Biffoni and Prof. Pirmohamed) This academic field aims to train, on a didactic and scientific level, specific professional skills for the knowledge and study of drugs on an experimental and clinical level. It deals with studying the mechanisms of action of drugs, the suitable methodologies for the evaluation of the effects of drugs, drug-toxicokinetics, the determination and control of posologies and the detection and evaluation of adverse reactions and their treatment; it also assesses the risk / benefit and cost / benefit ratio of drug interventions. The sector includes immunopharmacology as specific aspects. The inclusion of this academic field in the PhD in Network Oncology and Precision Medicine is necessary for the identification of therapeutic strategies designed specifically taking into consideration the needs of each oncological disease. And finally, it is a fundamental discipline, always in regards to personalized medicine, in order to optimize pharmacological efficacy and minimize its toxicity. The PhD Faculty Board is characterized by the participation of Professors from different academic fields (Scientific Disciplinary Sectors- SSD) in order to guarantee the convergence of medical-biological and scientific-technological knowledge. Knowledge fusion is the only tool that can provide us with an advantage in the face of the challenge of precision medicine in oncology. In this context, the aim to create an innovative programme that can improve precision medicine for the best oncologic patients’ healthcare is strongly supported by the existing active collaborations among the PhD faculty members. Moreover, PhD Faculty Board will create and promote collaborations within the PhD through the implementation of interdisciplinary and international research projects. Interdisciplinary research projects will be developed by the PhD Faculty members. The projects will cover the oncology medicine network and will be supervised by Harvard Medical School (with which Sapienza has framework agreement) where Prof. Loscalzo was the first in the world that applied the medicine network, in particular Prof Elisabeth Battinelli joined to the PhD in Network Oncology and Precision Medicine. A brief description of the Departments involved in the PhD program is reported DEPARTMENTS OF “SAPIENZA” UNIVERSITY Department of Experimental Medicine Head of Department: Prof Lenzi (n=7) Prof. M. Nuti, A. Rughetti, E. Ferretti, L. Pierelli, C. Napoletano, R. Gradini, F. Romanelli Personnel: eighty-three faculty members (22 Full professors, 29 associate professors, 32 Assistant professors) and twenty-one members of the academic staff, encompassing several academic disciplines. Faculty members are involved in teaching, research and clinical activities, with multidisciplinary and translational approach. The Department of Experimental Medicine represents Sapienza University in the European Consortium “LifeTime”. LifeTime is a pan-european Consortium established in 2018 by more than 90 centers for bio-medicine and 70 industrial partners, with the primary aim of revolutionize healthcare by targergeting specific pathologies utilizing cutting edge technologies. The Department of Experimental Medicine shares the LifeTime Consortium’s objectives and indeed Prof Nikolaus Rajewsky, founder and coordinator of said Consortium, was recruited in the external faculty board of the proposed PhD program. The Department of Experimental Medicine represents the Sapienza University of Rome in the LifeTime Consortium, a new pan-European consortium funded in 2018 and consisting of >90 leading research institutions in Biomedicine, supported by over 70 companies, that aims at revolutionizing healthcare by mapping, understanding, and targeting human cells during disease. The Department of Experimental Medicine shares the vision of the LifeTime Consortium and for this reason Prof Nikolaus Rajewsky, founding member and coordinator of said Consortium, was recruited as an external faculty member of the proposed PhD program. Prof. Nikolaus Rajewsky is a world-renowned scientist and for this reason he was awarded by the Sapienza University of Rome an honorary PhD in Human Biology and Medical Genetics in 2014. Teaching activity takes place in Masters’ degrees of Medicine, of healthcare Professions, post-graduation training courses, Specialization Schools of Endocrinology and Metabolic Diseases and Nutrition Science, PhD schools and First and Second level Master. Learning facilities at Department of Experimental Medicine include: - four classrooms with a booking system, available for lectures: Bignami Classroom, Vernoni Classroom, Caramia Classroom and Conti Classroom - one meeting room - one interdepartmental library (joined with Department of Molecular Medicine) at Pathology building, that offers wide reading room. This library is part of Sistema Bibliotecario della Sapienza (SBS) (Sapienza’s library system) and all activities are coordinated by an interdepartmental scientific committee. The library offers a wide collection of scientific books and journals, including the “campus” subscription to many bio-medical journals, that grants access to all Sapienza users. Moreover, a document delivery service is available at bib.stomed@uniroma1.it, allowing the access to scientific papers not included in Sapienza subscription portfolio. Research activity focuses on several key aspects of current medicine, such as clinical and molecular onco-immunology, oncogenomics, experimental, molecular and viral oncology, cancer physiopathology, system biology and molecular, cellular and clinica endocrinology. Facilities available for PhD students include benches, desks, computers with Sapienza internet access (including all Sapienza subscriptions) and Sapienza internet access for personal laptops. Laboratories are equipped for standard molecular biology and biochemistry and include refrigerators, freezers, -80°C freezers, laminar flood hoods, incubators and centrifuges. In addition, the following equipment is available: phase contrast and fluorescence microscope, thermal cycler, nano spectrophotometer, liquid nitrogen storage system, flow cytometry instruments, LSM 5 Exciter time-lapse live videomicroscopy, scanning electron microscope, automated nucleic acid purification platform (Maxwell, Promega), nucleic acid sequencing system Nanostring N counter Sprint Profiler (Diatech Lab Line), QX200 droplet digital PCR system (Biorad), LC-MS system with HPLC pump and mass spectrometry. Diagnostic and clinical activities take place in clinic and laboratories of cancer immunology and immunotherapy, oncogenomics, molecular physiopathology, clinical pathology and genetic and metabolic diseases, endocrinology, metabolic disease and nutrition science. Prof. Nuti is part of Fondazione per la Medicina Personalizzata (Personalized Medicine Foundation) whose focus is to identify the specific “identity” of each patient, leading to the best available treatment option. CLINICAL AND MOLECULAR MEDICINE DEPARTMENT (DMCM) Head of Department: Prof. Taurino Prof.Paolo Marchetti, Andrea Botticelli (N=2) The Department of Clinical and Molecular Medicine (DMCM) is composed of personnel (Full and Associate Professors, Researchers and Technicians) and laboratories as well as clinical structures located inside the Sant’Andrea Hospital. Academic disciplines of faculty members convey to molecular and cellular medicine, aiming at: improving knowledge on etiopathogenetic mechanisms in cardiovascular, hematological, respiratory, endocrine, nephrology, urology and ocological diseases, including immunological and hereditary basis; developing new methods in biomedicine and biotechnology for the identification of new diagnostic and therapeutic approaches for high impact diseases; developing of new teaching methods for medical and surgery schools. The main focus of DMCM is multidisciplinary, driven by the developement of strong interdisciplinary and translational topics. Research activity at DMCM is addressed to fulfill the growing needs for an excellence and modern medicine, and integrates with clinical activities at Sant’Andrea Hospital and teaching activities at Sapienza university. Prof. Marchetti is one of the founding Members of Fondazione per la Medicina Personalizzata (Personalized Medicine Foundation) whose focus is to identify the specific “identity” of each patient, leading to the best available treatment option. Facilities include the library of the Faculty of Medicine and Psychology, located at Sant’Andrea Hospital, 7 classroom accessible to students and one computer room. Department of Molecular Medicine Head of Department: Prof. Maroder Prof. Agnese Po (n=1) The Department of Molecular Medicine is composed of 78 faculty members (21 full professors, 31 associate professors and 26 assistant professors) and 44 technicians with specific cultural and technologic interdisciplinary expertise in emerging biomedical fields, such as molecular medicine, nano-biotechnology medicine, bioethics and history of medicine. Research activities at Department of Molecular Medicine focus on the integration between basic and translational research aimed at understanding and identifying the molecular level mechanisms of pathogenesis leading to genetic, infective, degenerative diseases and immune syndromes. Moreover, oncology is a major focus, including the study of the molecular and cellular mechanisms behind neoplasia and the comprehension of the role of immune and inflammatory response of the host, the control of the outbreak, growth and metastasis diffusion of tumours. Department of Molecular Medicine has been awarded by the Italian Ministry of University of the “Dipartimento di Eccellenza” (Excellence Department) grant, intended for the best performing departments in Italy, in the research area of “medical sciences”. Facilities at Department of Molecular Medicine include 1 classroom for teaching activities and seminars, a shared library with the department of Experimental Medicine, offering a wide collection of scientific books and journals, including the “campus” subscription to many bio-medical journals, and a document delivery granting access to scientific papers not included in Sapienza subscription portfolio. The Department of Molecular Medicine has several research laboratories equipped with cutting edge technologies, including: ViiA7 QPCR instrument (Thermofisher), Glomax luminometer (Promega), Chemidoc (Biorad) for UV and chemiluminescence detection,sterile tissue/cell culture rooms equipped with: laminar-flow hoods, incubators, centrifuge, refrigerator and freezer, cell counter, fully equipped biohazard cell culture laboratory BSL3 safety culture. Cryostorage container. The IncuCyte® S3 Live-Cell Analysis System (Essen Bioscience), Becton-Dickinson FACSCalibur and FACSAria Cytofluorimeters, Zeiss Observer Z.1 - LSM 5 Exciter time-lapse live videomicroscopy, Apotome for live imaging (Zeiss), Confocal Microscopy (including two-photon, Olympus), Digital microscope with a charge-coupled device (CCD) to record the images (Zeiss); Transgenic Mouse and Fully Equipped SPF Animal Facility. IVIS in vivo imaging system. Real Time Viia7, Luminometer (Promega Glowmax). PhD students will be granted access to lab spaces with benches and desks. Computers with Sapienza internet access (including all Sapienza subscriptions) and Sapienza internet access for personal laptops are also available. Department of Radiology, Oncology and Pathological Anatomy Head of Department: Prof. Giangaspero Prof. V.Panebianco, C.Giordano, M.Antonelli (n=3) The Department of Radiology, Oncology and Pathological Anatomy is made up of Professors from various scientific-disciplinary sectors in order to promote and coordinate teaching, research and assistance activities in the field of multimodal oncology, physio-pathological and biomolecular mechanisms at the base of oncological diseases and technological innovation of diagnostic and therapeutic imaging. Particular attention is paid to translational research in the oncology field, also through contracts and agreements with public and private institutions. The Department benefits of funding from the Ministry of Education, University and Research, and other public and private institutions . The Department offers 6 classrooms for teaching activities located in 2 buildings that make up the Department (Pathological Anatomy Building and Central Radiology Building) and also a library with a large reading room (Ghilarducci Library). In addition, the Department provides 4 fully equipped laboratories for histopathological, cytological and mutational investigations. Department of Computer, Control and Managment Engineering Head of Department: Prof. Catarci Prof. Maurizio Lenzerini, Irene Armerini (n=2) The Department of Computer, Control and Managment Engineering (DIAG) reflects its didactic and research development and its engineering rooting. Internationally renowned research groups in computer science, system science and managment science are active at DIAG. Basic research is its main goal, with a strong emphasis on interdisciplinary research, on applications that stimulate basic research, and on technology transfer and dissemination of results. Strong collaborations are maintained with researchers in other universities, research institutions and companies, in Italy and abroad. National and European research contracts and grants are routinely acquired by department, totaling about two million euros a year. On the educational side, the mission of DIAG is to train engineers for professional, research and teaching careers either in universities or in industries and public administration. DIAG provides 11 classrooms, 2 meeting rooms, 1 videoconference room, 7 visitors areas, 3 workshops and 11 research laboratories focused on all the department topics. The department library collects 11000 scientific volumes and provides open-access to almost 900 newspapers. DIAG has been selected among the 180 departments of excellence in Italy and will receive 8.5 million euros of funding, from the Ministry of Education, University and Research, destined to create an international pole of excellence in cybersecurity, strengthening and enhancing its outstanding expertise in its various research areas, with investments in human resources, infrastructures and highly qualified teaching activities. DIAG has an active scientific collaboration with Prof. Joseph Loscalzo, whose main focus is Network Medicine, through the framework agreement between Harvard University and Sapienza University of Rome. Department of Medical-Surgical Sciences and Translational Medicine Head of Department: Prof. Angelo Prof. N. Petrucciani (n=1) The Department aims to create a cultural and experimental continuum from basic biotechnological to applied research: "BENCH TO BEDSIDE" with the continuous training of doctors ready for future technological changes and the increased need for productive return of research. In addition, the Department evaluates of integrated care pathways in the territory for effective and efficient primary care models and translation research in the field of medical-surgical emergencies. The Department considers the centrality of the patient and consequent maximum knowledge and competence (culture) of the pathologies from which he is affected. The competence areas of the Department are structured in interconnected lines of research and teaching: 1. techno-biological area: surgical, endoscopic, radiological, radiotherapy, prosthetic materials; 2. Morpho-functional: imaging diagnostic, hardware, software, nuclear medicine, endoscopy; 3. Clinic: trials and studies on technological applications (materials, imaging, software, radiotherapy and radio-sectorial therapy) in integrated diagnostic-therapeutic pathways. Application of new Biomarkers to clinical decision-making in medicine 4. Global health care: the new paradigm for health and healthcare, rooted in the theoretical approach of social determinants of health, based on the principles set out in the Declaration of Alma Ata and substantiated by broad scientific evidence in the field of health promotion at individual level and / or community of life and work. 5. Territorial medicine: home care, family medicine, emergency-urgency network, control of diseases, disease prevention through vaccinations, cardiovascular prevention, secondary prevention in oncology, prevention of loss of self-sufficiency and in the various areas of life of the elderly, prevention of pathological addictions, prevention of inequalities, prevention at work. The Department collaborates with international and national groups for the development of materials, diagnostics, biomarkers, etc. which are currently being tested in research programs by some of the disciplinary components of the Department. The scientific-disciplinary sectors present in the Department are: Internal Medicine, Diagnostic Imaging and Radiotherapy, General Surgery, Thoracic Surgery, Digestive Diseases and Oncology: Digestive and Pulmonary. The Department offers 1 library located on the ground floor of the Sant’Andrea Hospital and 6 classrooms for teaching activities located inside the Sant'Andrea Hospital. ITALIAN EXTERNAL INSTITUTIONS Istituto Superiore di Sanità (I.S.S.) Department of Oncology and Molecular Medicine Dr.Biffoni The Department of Oncology and Molecular Medicine (OMM) at Istituto Superiore di Sanitá (ISS) is fully equipped for cellular and molecular biology research. A Reverse-Phase Protein Microarrays facility is fully operative, comprising a robotic arrayer, an automated staining station with a laser scanner. Laboratories are fully operational for archiving and storage of frozen and formalin-fixed paraffin-embedded biological specimens, laser-capture and histopathological analysis. Confocal and high content microscopy facility with capability of time lapse live cell imaging Flow cytometers for cell cycle and surface marker expression analyses; cell sorter for isolation of specific sub-populations of cells. Mass cytometer. Real-Time PCR cycler capable of accomodating 96- and 384-well plates Microplate reader for acquisition of fluorescence, chemiluminescence and radioactivity signal detection. High performance gel and blot imager for effortless detection of chemiluminescent, colorimetric and UV fluorescent gels and blots. Multiplex immunoassay instrument. Cryogenically cooled CCD equipped light-tight, low background imaging chamber with animal handling features such as a heated sample shelf and full gas anesthesia system. Individually ventilated system for animal care of immunodeficient mice and protocols for in vivo experiments already approved by competent authorities. University of Naples Federico II Department of Public Health Prof. Umberto Malapelle The Predictive Cytopathology and Molecular Pathology Unit, belonging to the Department of Public Health of the University of Naples Federico II, consists of four functional areas divided in relation to the different phases of the "workflow" for the preparation and preparation of the histological sample, extraction of nucleic acids, implementation of molecular biology methods for the analysis of genetic determinants functional to predictive molecular pathology and data analysis. The first functional area is used for the preparation of the sample for subsequent second level analysis. This area is equipped with an area for the preparation of the preparations by microtome cutting, an automatic instrument for the staining of the cyto/histological samples, an automatic system for immunohistochemical analysis, a space for the handling of the cyto / histological samples to be started for molecular biology investigations and for manual microdissection and consequent isolation of nucleic acids