Medical Biotechnology

Activity type

Attività formative affini o integrative

SSD

MED/46

Year

N/D

Semester

N/D

CFU

2

Hours distribution

16 classroom hours

Lecturers

ANTONIO FRANCESCO CAMPESE

Activity type

Discipline medico-chirurgiche e riproduzione umana

SSD

MED/04

Year

N/D

Semester

N/D

CFU

1

Hours distribution

8 classroom hours

Lecturers

ROBERTA SANTARELLI

Activity type

Attività formative affini o integrative

SSD

MED/46

Year

N/D

Semester

N/D

CFU

1

Hours distribution

8 classroom hours

Lecturers

SILVIA PICONESE

Activity type

Medicina di laboratorio e diagnostica

SSD

MED/08

Year

N/D

Semester

N/D

CFU

1

Hours distribution

8 classroom hours

Lecturers

ALESSANDRO CORSI

Activity type

Attività formative affini o integrative

SSD

MED/46

Year

N/D

Semester

N/D

CFU

2

Hours distribution

16 classroom hours

Lecturers

ENKE BALDINI

Activity type

Discipline medico-chirurgiche e riproduzione umana

SSD

MED/11

Year

N/D

Semester

N/D

CFU

2

Hours distribution

16 classroom hours

Lecturers

ANGELA LOMBARDI

Activity type

Discipline medico-chirurgiche e riproduzione umana

SSD

MED/15

Year

N/D

Semester

N/D

CFU

2

Hours distribution

16 classroom hours

Lecturers

ILARIA DEL GIUDICE

Activity type

Discipline veterinarie e riproduzione animale

SSD

VET/01

Year

N/D

Semester

N/D

CFU

1

Hours distribution

8 classroom hours

Lecturers

ANTONIO FRANCESCO CAMPESE

INTEGRATED COURSE: MOLECULAR MEDICINE AND ANIMAL MODELS OF DISEASE - REGENERATIVE MEDICINE
COORDINATOR: Prof.Roberta Santarelli
GOALS:
GENERAL OBJECTIVES
At the end of the course the student will know the fields of medicine in which biotechnology has brought about significant changes in the understanding and treatment of pathologies and the progress achieved in particular in: immunology, cardiology, haematology, oncology, endocrinology.
The student will know the characteristics of the main laboratory animal models as well as the techniques for the generation of the main types of genetically modified mouse models. The student will therefore be able to propose well-designed animal models for the pathophysiological study of human diseases and for the identification of therapeutic targets. Through frontal lessons the student will undertake a path of knowledge of pathologies and solution of biological problems. He will be able to understand how Hematology represented the study model of neoplastic pathologies and created a path from the molecular characterization of a disease to its cure. The student will know the model of chronic myeloid leukemia or acute promyeloid leukemia as a path in which biotechnology has produced exciting data. Likewise, in endocrinology, he will be able to verify how molecular biology has been pivotal for the characterization of some pathologies and to analyze possibilities as well as limits of the gene therapy approach in this field. In cardiology, the analysis of the pathophysiologic and molecular pathways of the main cardiovascular diseases and the regenerative medicine approaches, for the prevention of cardiac dysfunction after infarction, will allow for a general framework of new opportunities for designing innovative therapeutic approaches. The student will also know the main molecular mechanisms underlying immune evasion by Herpesviruses (used in this course as a model) and the persistence of these viruses in the host as well as the oncogenesis associated to EBV and KSHV infections and the new therapeutic approaches developed on the basis of this knowledge. Besides, the student will learn the main mechanisms involved in the regeneration and repair of tissues and organs and of the general principles of regenerative medicine and tissue engineering. The student must be able to design studies in order to suggest innovative pathogenetic and/or therapeutic pathways.

SPECIFIC OBJECTIVES
At the end of the course the student has to know the main biological, cellular and molecular mechanisms involved in the regeneration and repair of tissues and organs as well as the general principles of tissue engineering, especially skeletal; he has also to be able to critically evaluate the role of stem cells in tissue homeostasis and functional plasticity as well as their applicability in in vitro, pre-clinical and clinical trials, also in order to propose and develop tissue engineering solutions with reparative/regenerative purposes. Furthermore, the student has to know the main pathogenetic mechanisms of autoimmune diseases, chronic viral infections and tumors as well as the essential procedural elements for the generation, characterization and maintenance of mouse colonies. Furthermore, he has to know and be able to propose animal models useful for the study of human pathologies, e.g. for the study of immune cells in the aforementioned pathologies and of gamma-herpesvirus oncogenesis, as well as for the development of new therapeutic strategies.

(Dublin Descriptors 1) Knowledge and understanding
● Hematology (Del Giudice): Knowledge of normal and pathological hematopoiesis. Acute and chronic lymphoid leukemias as models for understanding the development of neoplasms and treatment pathways. Chronic myeloid leukemia and acute promyeloid leukemia as evidence of the possibility of cure of a disease when the causal mechanisms are known. Knowledge and understanding of the organization to perform hematopoietic stem cell transplants. Knowledge of the problems of homeostasis and thrombosis, especially as a link with cardiological pathologies.
● Pathologic Anatomy (Corsi): At the end of the course the student must be aware of the main cellular and molecular mechanisms, involved in the regeneration and repair of tissues and organs and of the general principles of regenerative medicine and tissue engineering, with particular attention to the skeletal system, including possible applications and limits.
● Immunology (Piconese). Know the mechanisms of development of physiological or aberrant immune responses in immunopathology. Know the main pathogenetic mechanisms of autoimmune diseases (systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis), chronic viral infections (HBV, HCV, etc.) and tumors. Know the role of the various arms of adaptive immunity (B cells, CD4, CD8 and Treg T cells) in the development of these pathologies. Know the main mouse models used for the study of immune cells in the aforementioned pathologies.
● Anatomy of laboratory animals (Campese). Course aimed at the knowledge of the basic aspects of functional anatomy of the most frequently used species in biomedical research with particular regard to mice, rats and rabbits. Description of macroscopic and microscopic anatomy, with the acquisition of concepts concerning the body structure of experimental animals, essential for anyone who has to deal with animal experimentation.
● Cardiology (Lombardi). At the end of the course the student will be able to recognize the molecular mechanisms underlying cardiovascular diseases and in particular, critically evaluating the role of animal models and regenerative medicine in pre-clinical and clinical research. At the end of the module the student will be able to discuss the scientific works presented during the course, identifying the rationale, the hypothesis, the main objectives and the future research directions.
● Animal models of disease (Campese). At the end of the educational path the student will have to know: advantages and limitations of genetically modified mouse models; the essential procedural elements for the generation, characterization and maintenance of mouse colonies; the specific characteristics of the main types of genetically manipulated mouse models, both conventional and conditional, as well as mouse models for the study of human pathologies; the basic knowledge of European and Italian legislation concerning the use of animals for scientific purposes.
● Models of immunoevasion and viral oncology (Santarelli). Upon completion of the course unit, the student must know: 1) the main molecular mechanisms that regulate the persistence of herpesviruses in the host; 2) the strategies through which these viruses subvert the immune response; 3) the molecular mechanisms leading to the development of tumors associated with EBV and KSHV infections; 4) the experimental approaches that have led to the development of currently adopted therapies, including cellular ones.
● At the end of the teaching module in Endocrinology (Baldini) the student will have to know: i) the pathophysiological bases of the main endocrine pathologies, including endocrine neoplasms, and in particular tumors of the thyroid gland; ii) the application of molecular biology techniques useful for the diagnosis and prognosis of endocrine neoplasms; iii) the application of biosensors in endocrinology; iv) gene therapy and regenerative medicine approaches for the treatment of endocrinopathies.

(Dublin Descriptors 2) Ability to apply knowledge and understanding
● Hematology: the student will be able to actively compose a research project in the hematological field on the model of the study paths learned. He will be able to participate for example in a PhD in Hematological Disciplines.
● Pathologic Anatomy: At the end of the course the student should be able to evaluate critically the role of stem cells in terms of tissue homeostasis and functional plasticity as well as their applicability in experimental in vitro, pre-clinical and clinical model in order to propose and elaborate tissue engineering solutions for reparative/regenerative purposes.
● Immunology: the student must be able to apply the acquired knowledge to the analysis and interpretation of results derived from experimental research. He must also be able to identify limits and criticalities in experimental models of immune-mediated diseases.
● Anatomy of laboratory animals: at the end of the course the student must be able to identify a topic of study (related if possible to his scientific interests and/or academic profile such as, for example, internship, experimental thesis, etc. ) and correlate it to the description of significant anatomical peculiarities for the development of the investigation.
● Cardiology: at the end of the course the student must be able to recognize the mechanisms of cardiovascular organ damage and in particular to critically evaluate the role of animal models and regenerative medicine in cardiology in terms of tissue homeostasis and functional plasticity as well as the possible applicability in pre-clinical and clinical experimental models, also in order to propose and develop tissue engineering solutions with reparative/regenerative purposes.
● Animal models of disease: the student must be able to apply the acquired knowledge to discriminate the specific characteristics, advantages and limitations of the different types of genetically modified mouse models and critically evaluate their potential role in the study of human pathologies; recognize the limits imposed by the legislator on animal experimentation;
● Models of immunoevasion and viral oncology: on the basis of the knowledge acquired following this course unit, the student must be able to discuss both the rationale and the experimental approaches of the scientific works presented during the course. Furthermore, he has to be able to demonstrate the ability to present and interpret the results in the scientific article chosen for the exam and propose a possible alternative experimental strategy as well.
● Endocrinology: Ability to apply knowledge and understanding: the student, starting from the current limits of molecular biology techniques and biotechnology in the field of diagnosis, therapy, prognosis and follow-up of endocrine pathologies, will have to acquire awareness of: a) the potential offered by animal models in the study and characterization of endocrinopathies; b) the usefulness of biotechnologies and their positive impact on patients' quality of life.

(Dublin Descriptors 3) Critical and judgment skills
The student will be able to connect the knowledge learned during this course and connect the animal models of study of the pathologies presented as well as establish the appropriate experimental strategy to answer research questions in various fields of study. The student will also be able to understand and make judgments on the possibility of generating "knock-out" or "knock-in" animals for a relevant gene in one of the pathologies of the disciplines that have been studied (Cardiology, Hematology, Endocrinology, Immunology, etc..). Finally, the student will be able to establish and judge the depth of the results and the correctness of results and of experimental approaches as well.

(Dublin Descriptors 4)
The student will be evaluated during the exam.

(Dublin Descriptors 5) Ability to continue studying autonomously throughout life
The indication for the use of scientific works published in journals with Impact Factor and reported on the PubMed website, on the topics covered by the lectures, for the preparation for the exam will produce the development of autonomous study skills and working models in the field of Biotechnology.

REQUIREMENTS
Students must possess the concepts of histology, human anatomy, physiology in order to understand the different pathological situations in the chosen specialist fields. In particular, they must have knowledge of the hematopoietic tissue, of the heart, of the endocrine and skeletal systems, of the immunocompetent populations and their role in the control of neoplastic diseases. Furthermore they must have knowledge of genetics, in the basic concepts of transmission of genetic characteristics to progeny, type and consequences of gene mutation, gene expression. Also, he must know the main morphological, immunophenotypic and molecular technologies, to build characterization pathways and hypothesize therapeutic solutions.
● Hematology. Notions of histology of hematopoietic tissue. Notions of Biochemistry, structure of nucleic acids, and proteins. Expression pathways of molecules. Cell cycle concepts. General concepts on immunocompetent populations. Concepts of genetics: structure of chromosomes, structure and expression of genes, concepts of the transmission of pathological genes.
● Pathologic Anatomy. In order to properly understand the teaching contents and achieve the learning objectives, at the beginning of the teaching activities the student must be in possession of the basic knowledge acquired and matured during the attendance of previous courses related to biology, cell and molecular, biochemistry, embryology, anatomy, histology, general pathology and pathological anatomy.
● Anatomy of laboratory animals. In order to optimize the teaching contents, the student must be in possession of the fundamental notions of macroscopic and structural organization of the human body as well as the basic principles of physiology in order to implement the comparative description of the anatomy of different species. This presupposes, in particular, an already acquired knowledge of the anatomical method and terminology.
● Immunology. Preparatory to the course is the knowledge of the cells and molecules of the adaptive immune system and their main physiological functions.
● Cardiology. Fundamental notions of biochemistry, genetics, general pathology, histology, anatomy and cardiovascular physiology.
● Animal models of disease. At the beginning of the teaching activity, the student must possess the basic knowledge of cellular and molecular biology, immunology, biochemistry, anatomy, physiology, general pathology.
● Models of immunoevasion and viral oncology. At the beginning of the teaching activity, the student must possess knowledge of cellular and molecular biology, immunology, biochemistry, anatomy, histology and general pathology.
● Endocrinology module. Students must have a good knowledge of Anatomy and Physiology of the endocrine glands. They must also have a good knowledge of the main molecular biology techniques.

Module: Molecular medicine and animal models of disease I
Aims and advantages of generating and using mouse models for studying human
diseases
- Ethical and legislative aspects related to animal experimentation (3R Rule,
Legislative Decree 26/2014)
- Genotyping techniques: PCR and Southern blotting
- Characterization and maintenance of genetically modified animal colonies
- Methodologies for generating "conventional" genetically modified mouse models:
transgenic mice and "knockout" mice
- "Conditional" and/or inducible genetically modified mouse models: the Cre/LoxP
system; conditional "knock-in" mice; Use of reporter genes (the IRES-GFP system)
- The CRISP/Cas9 system for editing the mouse genome

- Methodologies for genetic manipulation of the hematopoietic system: retroviral
vectors and bone marrow transplantation
- 3D cell cultures as a valid alternative to animal testing
- Examples of mouse models for studying human diseases: T-cell leukemias;
regulatory T cells; and experimental autoimmune diabetes


Module: Molecular medicine and animal models of disease II
Course unit: Models of immunoevasion and viral oncology (Santarelli)
Molecular mechanisms adopted by herpesviruses to escape immunosurveillance (2 hours). T
he Epstein-Barr virus (EBV): latency and tumorigenesis (2 hours).
Human Herpesvirus-8 (HHV-8 or KSHV) and associated malignancies (2 hours).
Herpesvirus microRNA: role in latent infection, immunoevasion and oncogenesis (2 hours).






Module: Molecular medicine and animal models of disease III
Introduction to the adaptive immune response. Main mechanisms of immunotolerance. Aberrant
immune responses in immunopathology.

B lymphocyte-mediated immunopathology: main functions, tolerance mechanisms, roles of
antibodies in autoimmunity. Pathogenesis of lupus and disease models. Rheumatoid arthritis
pathogenesis and disease models.
Immunopathology mediated by T helper lymphocytes: definition of subpopulations, polarization
mechanisms, roles in autoimmunity. Pathogenesis of multiple sclerosis and related animal models.
Immunoregulation and regulatory T lymphocytes: development, physiological roles, focus on the
suppression of anticancer immunosurveillance. Animal models of cancer.
Antiviral immunity mediated by CD8 T lymphocytes: activation mechanisms and main functions,
functional exhaustion, protective effects in viral infections. Mouse models of the CD8-mediated
response in viral infections.


Module: Molecular medicine and animal models of disease IV
Tissue homeostasis: general concepts. Control mechanisms of cell proliferation. Stem cells: biological properties, plasticity and role in tissue regeneration and repair. Regenerative medicine and tissue engineering, with particular reference to skeletal tissue: principles, applications and limits.


Module: Clinical and regenerative medicine I


Introduction to the endocrine system: notes on biosynthesis, secretion and mechanism of hormonal action.
Pathophysiology of the main endocrine axes.
Disorders of the hypothalamic-pituitary-thyroid axis: hyperthyroidism, hypothyroidism and autoimmune diseases.
Epidemiology, pathogenesis, diagnosis and therapy of tumors of the thyroid gland.
Molecular approaches useful for the diagnosis of thyroid carcinomas and their metastatic replications.
Screening of the RET gene in medullary thyroid carcinomas.
Use of recombinant human TSH in the follow-up of patients with differentiated thyroid cancer.
Use of biosensors in endocrinology.
Animal models of endocrine pathologies.
Gene therapy in endocrinology.
Applications of regenerative medicine in the field of endocrine pathologies.


Module: Clinical and regenerative medicine II


• Introduction to Regenerative Medicine; The Heart; The Vascular System; Blood

• Molecular Mechanisms and Regenerative Medicine Studies on Atherosclerosis and Endothelial Dysfunction

• Molecular Mechanisms and Regenerative Medicine Studies on Ischemia and Angina

• Molecular Mechanisms and Regenerative Medicine Studies Involved in Myocardial Infarction

• Molecular Mechanisms and Regenerative Medicine Studies Involved in Heart Failure

• Hypertension, Molecular Mechanisms, and Regenerative Medicine Approaches




Module: Clinical and regenerative medicine III


Hematopoiesis: General principles of hematopoiesis and mechanisms of cellular differentiation and maturation. The complete blood count as an indicator of hematopoiesis. Use of hematopoietic stem cells and growth factors for clinical use. The hematopoietic niche. Clonality and clonal hematopoiesis.

Chronic myeloid leukemia (CML) as a model of success in molecular medicine: diagnosis and pathogenesis; targeted therapy; measurable residual disease; mechanisms of resistance and clonal evolution.

Acute myeloid leukemia (AML) and lymphoid leukemia (ALL): diagnosis, prognosis, and therapeutic indications based on immunophenotypic, cytogenetic, and molecular characterization; some specific varieties of AML and ALL with therapeutic approaches aimed at the molecular target (targeted therapies).

The methodological and conceptual basis of minimal residual disease in leukemias.

Chronic lymphocytic leukemia: general clinical aspects of CLL; laboratory diagnostics; the biological basis of the clinical heterogeneity of CLL; therapeutic targets and mechanisms of action of biologics used in CLL (PERSONALIZED MEDICINE).

New immunotherapies in hematology: cell therapies (CAR-T) and antibodies (naked, drug-conjugated, bispecific, immune checkpoint inhibitors).

Use of hematopoietic stem cells in the treatment of hematologic patients: collection methods, histocompatibility; rejection and graft-versus-host disease (GVHD); antitumor effect (GVL).


Module: Clinical and regenerative medicine IV


Principles of systematic and comparative anatomy of the main animal species used
for experimental purposes, with particular emphasis on the description of the
anatomical structures of the mouse.
General Anatomy
- Principles of anatomical terminology; body organization; systems and organ
systems; organ structure.
- Integumentary system
- Locomotor system
- General information on bones, joints, and muscles
- Cardiovascular system
- Gross anatomy of the heart and great vessels
- Digestive, respiratory, urinary, and genital systems
- Endocrine and nervous systems

Module: Molecular medicine and animal models of disease I
Reviews and scientific articles (from international journals) and lesson slides


Module: Molecular medicine and animal models of disease II
Modelli di immunoevasione ed oncologia virale
● International reviews and scientific articles + PPT lesson slides

Modelli animali di malattia
● Reviews and scientific articles (from international journals) and lesson slides

Anatomia Patologica
Robbins Basic Pathology. Elsevier.

Ematologia.
Reviews on hematological journals published on PUBmed

Anatomia degli Animali da laboratorio
Chiasson RB: Laboratory Anatomy of the white rat - McGrow Hill
Barone R.: Atlas d'Anatomie du lapin - Masson
Cook M.: The Anatomy of the laboratory mouse - Academic Press
Popesko: Colour Atlas of Anatomy of small laboratory animals - Saunders

Immunologia
Cellular and Molecular Immunology Abbas 9th Edition (Elsevier)
Immunologia Cellulare e Molecolare Abbas Ottava Edizione (Masson)

Cardiologia
● Heart Regeneration. Stem Cells and Beyond. F. Engel. World Scientific
● Verranno inoltre suggeriti articoli, monografie e reviews su specifici argomenti trattati a lezione.

Endocrinologia
· M. D’Armiento, A. Lenzi: Guida allo studio dell’endocrinologia. Società Editrice Universo, III Edizione, 2012.
· Testi e/o articoli scientifici di approfondimento degli argomenti trattati a lezione forniti dal docente.


Module: Molecular medicine and animal models of disease III
Cellular and Molecular Immunology Abbas 9th Edition (Elsevier)
Immunologia Cellulare e Molecolare Abbas Ottava Edizione (Masson)


Module: Molecular medicine and animal models of disease IV
Robbins e Cotran. Le basi patologiche delle malattie. Edra Masson.
Lanza R, Langer R, Vacanti JP. Principles of Tissue Engineering. Academic Press.

last editions


Module: Clinical and regenerative medicine I


Texts and/or scientific articles providing in-depth analysis of the topics covered in class provided by the teacher.


Module: Clinical and regenerative medicine II


Reviews and scientific articles (from international journals) and powerpoint slides


Module: Clinical and regenerative medicine III


Reviews and scientific publications related to the topic suggested during the frontal lessons by the teacher.




Module: Clinical and regenerative medicine IV


Chiasson RB: Laboratory Anatomy of the white rat - McGrow Hill
Barone R.: Atlas d'Anatomie du lapin - Masson
Cook M.: The Anatomy of the laboratory mouse - Academic Press
Cozzi B.: Anatomia degli animali da laboratorio Casa Editrice Ambrosiana - Milano
Popesko: Colour Atlas of Anatomy of small laboratory animals - Saunders

Module: Molecular medicine and animal models of disease I
N/D
Module: Molecular medicine and animal models of disease II

Scientific articles related to topics included in the program will be recommended as a study tool for integrative purposes to frontal lessons and adopted text.



Module: Molecular medicine and animal models of disease III
N/D
Module: Molecular medicine and animal models of disease IV
Scientific articles related to topics included in the program will be recommended as a study tool for integrative purposes to frontal lessons and adopted texts.


Module: Clinical and regenerative medicine I


N/D
Module: Clinical and regenerative medicine II


N/D
Module: Clinical and regenerative medicine III


N/D
Module: Clinical and regenerative medicine IV


N/D

The teaching is essentially based on in-class lectures characterized by a strong interactive component between the teacher and the students. Other teaching methods may include group or individual work on the analysis of methods and results of publications in international scientific journals

Attendance is verified by the teacher through signature/call sheets on updated lists provided by the Teaching Secretariat. The certificate of attendance, of at least 67% of the teaching activities of the teaching course, is necessary for the student to take the relative exam.

EVALUATION
The exam will consist of an oral test, during which questions will be asked to assess the knowledge and understanding of the topics covered in class. The student has to demonstrate that he has acquired a knowledge of the topics proposed, with critical ability, and be able to propose interpretations and/or solutions to problems related to the subjects studied. For some modules (Santarelli, Corsi and a part of the Campese exam), the oral exam will consist of a critical analysis of a scientific article selected by the student related to the course programme.
The evaluation will take into account: a) the ability to critically discuss the methods and results of the selected scientific article; b) the knowledge of the topics covered by the exam questions; c) the adequacy of the answer to each of the questions in relation to the skills that should be acquired at the end of the course; d) the logical reasoning to answer questions; e) the use of appropriate language.
All modules must be passed with a score of ≥ 18/30. The final grade will consist of the average of the individual modules. The score 30 cum laude is intended for students who are able to logically and coherently connect the topics covered. The property of scientific language will also be a parameter subject to evaluation

Course unit: Models of immunoevasion and viral oncology (Santarelli)
Regarding the presented article, what experiments would you have conducted if you had been the author of this paper?

Course unit: Pathologic anatomy (Corsi)
Which comments would you have made if you had been one of the reviewers of the presented article?

Course unit:Anatomy of laboratory animals (Campese)
- Discuss a topic based on the use of a laboratory animal model on the basis of the content of related scientific literature

Course unit: Animal models of disease (Campese)
-Aims, features and techniques for the generation of transgenic mice
-Aims, features and techniques for the generation of knock-out mice
-The meaning of the 3R's principles

Course unit: Cardiology (Lombardi)
• Molecular mechanisms of hypertension
• Animal models used in the study of atherosclerosis
• Examples of regenerative medicine in cardiology not cell-based

Module: Molecular medicine and animal models of disease I

• Aims and advantages of genetically modified mouse models


• Ethics and law on animal testing in Italy: the 3Rs principle and Legislative Decree 26/2014


• Generation and screening of conventional transgenic mice


• Generation and selection of conventional knockout models


• Conditional knockout models: the Cre/loxP system and inducible models


• Retroviral vectors in the genetic manipulation of mouse models; the IRES sequences


• The CRISPR/Cas9 system; 3D cell cultures


• Immunodeficient mouse models and PDX;examples of mouse models for studying human diseases: Notch and T-cell leukemia

• The lessons will be two hours long, once or twice a weekCourse unit: Models of immunoevasion and viral oncology (Santarelli) Molecular mechanisms adopted by herpesviruses to escape immunosurveillance (2 hours). The Epstein-Barr virus (EBV): latency and tumorigenesis (2 hours). Human Herpesvirus-8 (HHV-8 or KSHV) and associated malignancies (2 hours). Herpesvirus microRNA: role in latent infection, immunoevasion and oncogenesis (2 hours).
  • Books: Reviews and scientific publications related to the topic suggested during the frontal lessons by the teacher+Teaching materials provided by the teacher

• Introduction to the adaptive immune response. Main mechanisms of immunotolerance. Aberrantimmune responses in immunopathology.(2 hours)B lymphocyte-mediated immunopathology: main functions, tolerance mechanisms, roles ofantibodies in autoimmunity. Pathogenesis of lupus and disease models. Rheumatoid arthritispathogenesis and disease models.(2 hours)Immunopathology mediated by T helper lymphocytes: definition of subpopulations, polarizationmechanisms, roles in autoimmunity. Pathogenesis of multiple sclerosis and related animal models.Immunoregulation and regulatory T lymphocytes: development, physiological roles, focus on thesuppression of anticancer immunosurveillance. Animal models of cancer.(2 hours)Antiviral immunity mediated by CD8 T lymphocytes: activation mechanisms and main functions,functional exhaustion, protective effects in viral infections. Mouse models of the CD8-mediatedresponse in viral infections.(2 hours)

• Tissue homeostasis. Regeneration and repair. - 2 hours
  • Books: Adopted texts and scientific publications suggested during the frontal lessons.


• Cell cycle and regulation of cell proliferation. Growth factors and transcription factors. Extracellular matrix and cell-matrix interactions. Mechanisms of tissue and organ regeneration and repair. - 2 hours
  • Books: Adopted texts and scientific publications suggested during the frontal lessons.


• Stem cells: general concepts. - 2 hours
  • Books: Adopted texts and scientific publications suggested during the frontal lessons.


• Regenerative medicine and tissue engineering with particular reference to skeletal tissue: principles, applications and limitations. - 2 hours
  • Books: Adopted texts and scientific publications suggested during the frontal lessons.

• First lesson - Pathophysiology of the main endocrine axes.
  • Books: Slides illustrating the topics covered with marginal notes and links to reference texts.


• Second lesson - Hypothalamic-pituitary-thyroid axis disorders: hyperthyroidism, hypothyroidism, and autoimmune diseases.Epidemiology and pathogenesis of thyroid tumors; molecular approaches for the diagnosis of thyroid carcinomas and their metastatic replication.


• Third lesson - RET gene screening in medullary thyroid carcinomas. Use of recombinant human TSH in the follow-up of patients with differentiated thyroid carcinoma.


• Fourth, fifth and sixth lesson - Animal models of endocrine pathologies.


• Seventh and eight lesson - Gene therapy in endocrinology. Applications of regenerative medicine in endocrine diseases.

• ·      
  Molecular mechanisms of cardiac
  diseases (4 hours)
  
  ·      
  Animal models used in preclinical
  studies (4 hours)
  
  ·      
  Rigenerative therapy in
  cardiology: cell-based therapies (3 hours)
  
  ·      
  Rigenerative therapy in
  cardiology: non cell-based therapies (3 hours)
  
  ·      
  Bioengineering approaches (2 hours)
  • Books: Reviews and scientific articles (from
    
    international journals) and lesson slides

• Hematopoieis (2 hours)•General principles of hematopoiesis•Use of hematopoietic stem cells and growth factors for clinical use•Hematopoietic niche•Clonality and clonal hematopoiesis
  • Books: Reviews and scientific publications related to the topic suggested during the frontal lessons by the teacher.


• Chronic myeloid leukemia (CML) as a model for molecular medicine (2 hours)•Diagnosis and pathogenesis•Targeted therapy•Measurable residual disease•Mechanisms of resistance


• Acute leukemias: diagnosis, prognosis, and treatment options based on immunophenotypic, cytogenetic, and molecular characterization (2 hours).- Understand the diagnostic process and laboratory tests relevant to the diagnosis and classification of acute myeloid leukemias (AML).- Understand some specific varieties of AML with specific therapeutic approaches aimed at specific genetic lesions (targeted therapies).


• Acute leukemias  (2 hours).- Understand the diagnostic process and laboratory tests relevant to the diagnosis and classification of acute lymphoid leukemias (ALL).- Understand some specific varieties of ALL with specific therapeutic approaches aimed at specific genetic lesions (targeted therapies).- Understand the methodological and conceptual basis of minimal residual disease.


• Chronic Lymphocytic Leukemia (2 hours)-Know the general clinical aspects of CLL-Know the diagnostic process and laboratory tests relevant to the differential diagnosis of absolute lymphocytosis and the diagnosis of CLL-Understand the biological basis of the clinical heterogeneity of CLL (PROGNOSIS)-Know the targets and understand the mechanisms of action of biologics used in CLL (PERSONALIZED MEDICINE)


• New immunotherapy strategies in lymphoid neoplasms (2 hours)-Monoclonal antibodies (naked and drug-conjugated)-Bispecific antibodies-CAR-T cells-Check-point inhibitors


• Hematopoietic Stem Cell Transplant (2 hours)- Types of Hematopoietic Stem Cell Transplant- Histocompatibility- Rejection- Graft-versus-Host Disease (GVHD)- Antitumor Effect (GVL)

• General anatomy of the mouse and notes on that of the rat and rabbit- Principles of anatomical terminology; body organization; systems and organ systems; organ structure.


• - Integumentary system- Locomotor system


• - General information on bones, joints, and muscles- Cardiovascular system- Gross anatomy of the heart and great vessels


• - Digestive, respiratory, urinary, and genital systems- Endocrine and nervous systems